Efficacy of Parent-Child Interaction Therapy with Chinese ADHD Children: Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Ng, Gene S. H.; Choi, S. Y.

2017-01-01

Purpose: This study aimed to evaluate the efficacy of Parent-Child Interaction Therapy (PCIT) in Chinese children with attention-deficit/hyperactivity disorder (ADHD) or ADHD features. Methods: This study adopted a randomized controlled trial design without blinding. Participants were randomized into either the intervention group (n = 32) and…

[Randomized, controlled clinical trials with observational follow-up investigations for evaluating efficacy of antihyperglycaemic treatment. II. Features of and lessons from the follow-up investigations].

PubMed

Jermendy, György

2018-04-01

Although the outcomes of the follow-up investigation period of the randomized clinical studies for evaluating the efficacy of a treatment or an antidiabetic drug may be confounded or potentially biased by several factors, the results are widely accepted by the diabetes community. In line with the theory of metabolic memory or metabolic legacy, early and intensive antihyperglycaemic treatment should be provided for all diabetic patients as this strategy can result in beneficial effects even in the long run. The recent cardiovascular safety trials with new, innovative antidiabetic drugs differ in several aspects from the former efficacy studies. Ten cardiovascular safety trials were completed so far enabling to define their unique and common features. It can be anticipated that the era of randomized, controlled efficacy studies with observational follow-up investigations came to an end in diabetes research. Nowadays, cardiovascular safety trials are in the focus of clinical research in diabetology and results of several ongoing studies are expected with interest in the near future. Orv Hetil. 2018; 159(16): 615-619.

Efficacy of killed whole-parasite vaccines in the prevention of leishmaniasis: a meta-analysis.

PubMed

Noazin, Sassan; Khamesipour, Ali; Moulton, Lawrence H; Tanner, Marcel; Nasseri, Kiumarss; Modabber, Farrokh; Sharifi, Iraj; Khalil, E A G; Bernal, Ivan Dario Velez; Antunes, Carlos M F; Smith, Peter G

2009-07-30

Despite decades of investigation in countries on three continents, an efficacious vaccine against Leishmania infections has not been developed. Although some indication of protection was observed in some of the controlled trials conducted with "first-generation" whole, inactivated Leishmania parasite vaccines, convincing evidence of protection was lacking. After reviewing all previously published or unpublished randomized, controlled field efficacy clinical trials of prophylactic candidate vaccines, a meta-analysis of qualified trials was conducted to evaluate whether there was some evidence of protection revealed by considering the results of all trials together. The findings indicate that the whole-parasite vaccine candidates tested do not confer significant protection against human leishmaniasis.

Antibiotics for human toxoplasmosis: a systematic review of randomized trials

PubMed Central

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

2013-01-01

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. PMID:23816507

First generation leishmaniasis vaccines: a review of field efficacy trials.

PubMed

Noazin, Sassan; Modabber, Farrokh; Khamesipour, Ali; Smith, Peter G; Moulton, Lawrence H; Nasseri, Kiumarss; Sharifi, Iraj; Khalil, Eltahir A G; Bernal, Ivan Dario Velez; Antunes, Carlos M F; Kieny, Marie Paule; Tanner, Marcel

2008-12-09

First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates which have undergone phase 3 clinical trial evaluation. Although the studies demonstrated the safety of the vaccines and several studies showed reasonable immunogenicity and some indication of protection, an efficacious prophylactic vaccine is yet to be identified. Despite this overall failure, these trials contributed significantly to increasing knowledge on human leishmaniasis immunology. To provide a collective view, this review discusses the methods and findings of field efficacy trials of first generation leishmaniasis vaccine clinical trials conducted in the Old and New Worlds.

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

PubMed

Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

2016-11-23

Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cognitive-Behavioral Therapy for Intermittent Explosive Disorder: A Pilot Randomized Clinical Trial

ERIC Educational Resources Information Center

McCloskey, Michael S.; Noblett, Kurtis L.; Deffenbacher, Jerry L.; Gollan, Jackie K.; Coccaro, Emil F.

2008-01-01

No randomized clinical trials have evaluated the efficacy of psychotherapy for intermittent explosive disorder (IED). In the present study, the authors tested the efficacy of 12-week group and individual cognitive-behavioral therapies (adapted from J. L. Deffenbacher & M. McKay, 2000) by comparing them with a wait-list control in a randomized…

Evaluation of early efficacy endpoints for proof-of-concept trials.

PubMed

Chen, Cong; Sun, Linda; Li, Chih-Lin

2013-03-11

A Phase II proof-of-concept (POC) trial usually uses an early efficacy endpoint other than a clinical endpoint as the primary endpoint. Because of the advancement in bioscience and technology, which has yielded a number of new surrogate biomarkers, drug developers often have more candidate endpoints to choose from than they can handle. As a result, selection of endpoint and its effect size as well as choice of type I/II error rates are often at the center of heated debates in design of POC trials. While optimization of the trade-off between benefit and cost is the implicit objective in such a decision-making process, it is seldom explicitly accounted for in practice. In this research note, motivated by real examples from the oncology field, we provide practical measures for evaluation of early efficacy endpoints (E4) for POC trials. We further provide optimal design strategies for POC trials that include optimal Go-No Go decision criteria for initiation of Phase III and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology is used for illustration purpose, the same idea developed in this research note also applies to similar situations in other therapeutic areas or in early-stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.

Preparing for future efficacy trials of severe malaria vaccines.

PubMed

Gonçalves, Bronner P; Prevots, D Rebecca; Kabyemela, Edward; Fried, Michal; Duffy, Patrick E

2016-04-07

Severe malaria is a major cause of mortality in children, but comprises only a small proportion of Plasmodium falciparum infections in naturally exposed populations. The evaluation of vaccines that prevent severe falciparum disease will require clinical trials whose primary efficacy endpoint will be severe malaria risk during follow-up. Here, we show that such trials are feasible with fewer than 1000 participants in areas with intense malaria transmission during the age interval when severe malaria incidence peaks. Published by Elsevier Ltd.

Recruitment failure and futility were the most common reasons for discontinuation of clinical drug trials. Results of a nationwide inception cohort study in the Netherlands.

PubMed

van den Bogert, Cornelis A; Souverein, Patrick C; Brekelmans, Cecile T M; Janssen, Susan W J; Koëter, Gerard H; Leufkens, Hubert G M; Bouter, Lex M

2017-08-01

The objective of the study was to identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol. All clinical drug trials in the Netherlands, reviewed by institutional review boards in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (Central Committee on Research Involving Human Subjects [CCMO]) and a questionnaire to the principal investigators. Reasons for trial discontinuation were the primary outcome of the study. Three reasons for discontinuation were analyzed separately: all cause, recruitment failure, and efficacy related (when an interim analysis had demonstrated futility or superiority). Among the efficacy-related discontinuations, we examined whether the data monitoring committee, the stopping rule, and the moment of the interim analysis in the trial progress were specified in the trial protocol. Of the 574 trials, 102 (17.8%) were discontinued. The most common reasons were recruitment failure (33 of 574; 5.7%) and solely efficacy related (30 of 574; 5.2%). Of the efficacy-related discontinuations, 10 of 30 (33.3%) of the trial protocols reported all three aspects in the trial protocol, and 20 of 30 (66.7%) reported at least one aspect in the trial protocol. One out of five clinical drug trials is discontinued before the planned trial end, with recruitment failure and futility as the most common reasons. The target sample size of trials should be feasible, and interim analyses should be adequately described in trial protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye: a systematic review of randomized clinical trials.

PubMed

Wu, Di; Chen, Wang Qi; Li, Ryan; Wang, Yan

2015-06-01

To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye. Randomized clinical trials (RCTs) from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were identified to evaluate the efficacy and safety of topical administration of diquafosol to patients with dry eyes. Data evaluation was based on endpoints including Schirmer test, tear film break-up time, ocular surface staining score, subjective symptom score, and adverse events. A total of 8 RCTs involving 1516 patients were selected based on the prespecified criteria. Significant improvement of Schirmer test values and tear film break-up time were reported in 40% (2 of 5) and 80% (4 of 5) studies, respectively. Ocular surface staining scores significantly decreased in 100% (fluorescein corneal staining, 6 of 6; Rose Bengal corneal and conjunctival staining, 4 of 4) RCTs. Symptoms significantly improved in 75% (6 of 8) RCTs in patients with dry eyes. No severe adverse events were reported with the concentration of diquafosol from 0.5% to 5%. Heterogeneity in study design prevented meta-analysis from statistical integration and summarization. Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.

TREATMENT TRIAL AND LONG-TERM FOLLOW-UP EVALUATION AMONG COMORBID YOUTH WITH MAJOR DEPRESSION AND A CANNABIS USE DISORDER.

PubMed

Cornelius, Jack R; Salloum, Ihsan M; Ferrell, Robert; Douaihy, Antoine B; Hayes, Jeanie; Kirisci, Levent; Horner, Michelle; Daley, Dennis C

2012-01-01

This study compared the acute phase (12-week) and the long-term (1 year) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the cannabis use of youth with comorbid major depressive disorder (MDD) and an cannabis use disorder (CUD)(cannabis dependence or cannabis abuse). We hypothesized that fluoxetine would demonstrate efficacy in the acute phase trial and at the 1-year follow-up evaluation. Data is also provided regarding the prevalence of risky sexual behaviors in our study sample. We recently completed the first double-blind placebo-controlled study of fluoxetine in adolescents and young adults with comorbid MDD/CUD. A total of 70 persons participated in the acute phase trial, and 68 of those persons (97%) also participated in the 1-year follow-up evaluation. Results of the acute phase study have already been presented (Cornelius, Bukstein, et al., 2010), but the results of the 1 year follow-up assessment have not been published previously. All participants in both treatment groups also received manual-based cognitive behavioral therapy (CBT) and motivation enhancement therapy (MET) during the 12-week course of the study. The 1-year follow-up evaluation was conducted to assess whether the clinical improvements noted during the acute phase trial persisted long term. During the acute phase trial, subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in depressive symptoms and in cannabis-related symptoms. However, no significant difference was noted between the floxetine group and the placebo group on any treatment outcome variable during the acute phase trial. End of study levels of depressive symptoms were low in both the fluoxetine group and the placebo group. Most of the clinical improvements in depressive symptoms and for cannabis-related symptoms persisted at the 1-year follow-up evaluation. Fluoxetine did not demonstrate greater efficacy than placebo for treating either the depressive symptoms or the cannabis-related symptoms of our study sample during the acute phase study or at the 1-year follow-up assessment. The lack of a significant treatment effect for fluoxetine may at least in part reflect efficacy of the CBT/MET psychotherapy. A persistence of the efficacy of the acute phase treatment was noted at the 1-year follow-up evaluation, suggesting long-term effectiveness for the CBT/MET psychotherapy.

Does the use of efficacy or effectiveness evidence in cost-effectiveness analysis matter?

PubMed

Dilokthornsakul, Piyameth; Chaiyakunapruk, Nathorn; Campbell, Jonathan D

2017-01-02

To test the association of clinical evidence type, efficacy-based or effectiveness-based ("E"), versus whether or not asthma interventions' cost-effectiveness findings are favorable. We conducted a systematic review of PubMed, EMBASE, Tufts CEA registry, Cochrane CENTRAL, and the UK National Health Services Economic Evaluation Database from 2009 to 2014. All cost-effectiveness studies evaluating asthma medication(s) were included. Clinical evidence type, "E," was classified as efficacy-based if the evidence was from an explanatory randomized controlled trial(s) or meta-analysis, while evidence from pragmatic trial(s) or observational study(s) was classified as effectiveness-based. We defined three times the World Health Organization cost-effectiveness willingness-to-pay (WTP) threshold or less as a favorable cost-effectiveness finding. Logistic regression tested the likelihood of favorable versus unfavorable cost-effectiveness findings against the type of "E." 25 cost-effectiveness studies were included. Ten (40.0%) studies were effectiveness-based, yet 15 (60.0%) studies were efficacy-based. Of 17 studies using endpoints that could be compared to WTP threshold, 7 out of 8 (87.5%) effectiveness-based studies yielded favorable cost-effectiveness results, whereas 4 out of 9 (44.4%) efficacy-based studies yielded favorable cost-effectiveness results. The adjusted odds ratio was 15.12 (95% confidence interval; 0.59 to 388.75) for effectiveness-based versus efficacy-based achieving favorable cost-effectiveness findings. More asthma cost-effectiveness studies used efficacy-based evidence. Studies using effectiveness-based evidence trended toward being more likely to disseminate favorable cost-effective findings than those using efficacy. Health policy decision makers should pay attention to the type of clinical evidence used in cost-effectiveness studies for accurate interpretation and application.

Efficacy and safety of biologic therapies for systemic lupus erythematosus treatment: systematic review and meta-analysis.

PubMed

Borba, Helena Hiemisch Lobo; Wiens, Astrid; de Souza, Thais Teles; Correr, Cassyano Januário; Pontarolo, Roberto

2014-04-01

The objectives of this study were to evaluate the efficacy, safety, and tolerability of biologic drugs compared with placebo for systemic lupus erythematosus (SLE) treatment. A systematic review evaluating the efficacy and safety of biologic therapies compared with placebo in adult SLE patients treatment was performed. Data from studies performed before September 2013 were collected from several databases (MEDLINE, Cochrane Library, SCIELO, Scopus, and International Pharmaceutical Abstracts). Study eligibility criteria included randomized, double-blind, placebo-controlled trials; regarding treatment with biologic agents in SLE adult patients; and published in English, German, Portuguese, and Spanish. Extracted data were statistically analyzed in a meta-analysis using the Review Manager (RevMan) 5.1 software. Efficacy outcomes included the SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index) score, the SRI (Systemic Lupus Erythematosus Responder Index), normalization of low C3 (<90 mg/dL), anti-double-stranded DNA positive to negative, and no new BILAG (British Isles Lupus Assessment Group index) 1A or 2B flares. Data on safety profile included adverse events, serious and severe adverse events, death, malignancy, infections, and infusion reactions. We also evaluated withdrawals from treatment due to lack of efficacy or adverse events. Thirteen randomized placebo-controlled trials met the criteria for data extraction for systematic review. A meta-analysis regarding the efficacy and safety of belimumab compared with placebo involving four of these trials was undertaken and the remainder contributed to a meta-analysis of the safety of biologic agents. In addition, two trials allowed the performance of a meta-analysis regarding the efficacy and safety of rituximab compared with placebo. Belimumab was more effective than placebo in most evaluated outcomes. No significant differences in the safety and tolerability data were observed between the belimumab and placebo groups. No differences were observed between the rituximab and placebo groups for the efficacy outcomes or safety parameters. Extracted data from the 13 studies were pooled, allowing assessment of the safety of biologic drugs. The meta-analysis revealed a satisfactory safety profile of these agents when used for SLE treatment, as there were no significant differences between the two evaluated groups (biologic agents and placebo) for all outcomes analyzed. Belimumab exhibited a satisfactory profile regarding efficacy, safety, and tolerability. Rituximab showed no superiority over placebo in terms of efficacy, despite its suitable safety profile. Biologic agents exhibited a good safety profile for SLE treatment, indicating that these agents are promising therapies and should be further investigated.

Efficacy of the HPV-16/18 Vaccine: Final according to protocol results from the blinded phase of the randomized Costa Rica HPV-16/18 Vaccine Trial

PubMed Central

Hildesheim, Allan; Wacholder, Sholom; Catteau, Gregory; Struyf, Frank; Dubin, Gary; Herrero, Rolando

2014-01-01

Background A community-based randomized trial was conducted in Costa Rica to evaluate the HPV-16/18 AS04-adjuvanted vaccine (NCT00128661). The primary objective was to evaluate efficacy of the vaccine to prevent cervical intraepithelial neoplasia 2 or more severe disease (CIN2+) associated with incident HPV-16/18 cervical infections. Secondary objectives were to evaluate efficacy against CIN2+ associated with incident cervical infection by any oncogenic HPVs and to evaluate duration of protection against incident cervical infection with HPV-16/18. Vaccine safety and immunogenicity over the 4-year follow-up were also evaluated. Methods We randomized (3,727 HPV arm; 3,739 Control arm), vaccinated (HPV-16/18 or Hepatitis A) and followed (median 53.8 months) 7,466 healthy women aged 18-25 years. 5,312 women (2,635 HPV arm; 2,677 Control arm) were included in the according to protocol analysis for efficacy. The full cohort was evaluated for safety. Immunogenicity was considered on a subset of 354 (HPV-16) and 379 (HPV-18) women. HPV type was assessed by PCR on cytology specimens. Immunogenicity was assessed using ELISA and inhibition enzyme immunoassays. Disease outcomes were histologically confirmed. Vaccine efficacy and 95% confidence intervals (95%CI) were computed. Results Vaccine efficacy was 89.8% (95% CI: 39.5 - 99.5; N=11 events total) against HPV-16/18 associated CIN2+, 59.9% (95% CI: 20.7 - 80.8; N=39 events total) against CIN2+ associated with non-HPV-16/18 oncogenic HPVs and 61.4% (95% CI: 29.5-79.8; N=51 events total) against CIN2+ irrespective of HPV type. The vaccine had an acceptable safety profile and induced robust and long-lasting antibody responses. Conclusions Our findings confirm the high efficacy and immunogenicity of the HPV-16/18 vaccine against incident HPV infections and cervical disease associated with HPV-16/18 and other oncogenic HPV types. These results will serve as a benchmark to which we can compare future findings from ongoing extended follow-up of participants in the Costa Rica trial. Trial Registration Registered with clinicaltrials.gov: NCT00128661 PMID:25018097

Computer-Assisted Learning in Elementary Reading: A Randomized Control Trial

ERIC Educational Resources Information Center

Shannon, Lisa Cassidy; Styers, Mary Koenig; Wilkerson, Stephanie Baird; Peery, Elizabeth

2015-01-01

This study evaluated the efficacy of Accelerated Reader, a computer-based learning program, at improving student reading. Accelerated Reader is a progress-monitoring, assessment, and practice tool that supports classroom instruction and guides independent reading. Researchers used a randomized controlled trial to evaluate the program with 344…

Ebola Virus Infection: a review on the pharmacokinetic and pharmacodynamic properties of drugs considered for testing in human efficacy trials

PubMed Central

Madelain, Vincent; Nguyen, Thi Huyen Tram; Olivo, Anaelle; De Lamballerie, Xavier; Guedj, Jeremie; Taburet, Anne-Marie; Mentré, France

2016-01-01

The 2014–2015 outbreak of Ebola virus disease (EVD) is the largest epidemic to date in terms of number of cases, of death and affected areas. In October 2015, no antiviral agents had proven an antiviral efficacy in patients. However in September 2014 WHO inventoried and regularly updated since then a list of potential drug candidates with demonstrated antiviral efficacy in vitro or in animal models. This includes agents belonging to various therapeutic classes, namely direct antiviral agents (favipiravir and BCX4430), combination of antibodies (ZMapp), type I interferons, RNA interference-based drugs (TKM-Ebola and AVI-7537) and anticoagulant drug (rNAPc2). Here, we review the pharmacokinetic and pharmacodynamic information that are presently available on these drugs, using data obtained in healthy volunteers for pharmacokinetics and data obtained in human clinical trials or animal models for pharmacodynamics. Future studies evaluating these drugs in clinical trials will be critical to confirm their efficacy in humans, propose appropriate doses and evaluate the possibility of treatment combinations. PMID:26798032

Study protocol for a pragmatic randomised controlled trial evaluating efficacy of a smoking cessation e-‘Tabac Info Service’: ee-TIS trial

PubMed Central

Cambon, L; Bergman, P; Le Faou, Al; Vincent, I; Le Maitre, B; Pasquereau, A; Arwidson, P; Thomas, D; Alla, F

2017-01-01

Introduction A French national smoking cessation service, Tabac Info Service, has been developed to provide an adapted quitline and a web and mobile application involving personalised contacts (eg, questionnaires, advice, activities, messages) to support smoking cessation. This paper presents the study protocol of the evaluation of the application (e-intervention Tabac Info Service (e-TIS)). The primary objective is to assess the efficacy of e-TIS. The secondary objectives are to (1) describe efficacy variations with regard to users' characteristics, (2) analyse mechanisms and contextual conditions of e-TIS efficacy. Methods and analyses The study design is a two-arm pragmatic randomised controlled trial including a process evaluation with at least 3000 participants randomised to the intervention or to the control arm (current practices). Inclusion criteria are: aged 18 years or over, current smoker, having completed the online consent forms, possessing a mobile phone with android or apple systems and using mobile applications, wanting to stop smoking sooner or later. The primary outcome is the point prevalence abstinence of 7 days at 6 months later. Data will be analysed in intention to treat (primary) and per protocol analyses. A logistic regression will be carried out to estimate an OR (95% CI) for efficacy. A multivariate multilevel analysis will explore the influence on results of patients' characteristics (sex, age, education and socioprofessional levels, dependency, motivation, quit experiences) and contextual factors, conditions of use, behaviour change techniques. Ethics and dissemination The study protocol was reviewed by the ethical and deontological institutional review board of the French Institute for Public Health Surveillance on 18 April 2016. The findings of this study will allow us to characterise the efficacy of e-TIS and conditions of its efficacy. These findings will be disseminated through peer-reviewed articles. Trial registration number NCT02841683; Pre-results. PMID:28237958

GET.ON Mood Enhancer: efficacy of Internet-based guided self-help compared to psychoeducation for depression: an investigator-blinded randomised controlled trial

PubMed Central

2014-01-01

Background Major depressive disorder (MDD) imposes a considerable disease burden on individuals and societies. A large number of randomised controlled trials (RCTs) have shown the efficacy of Internet-based guided self-help interventions in reducing symptoms of depression. However, study quality varies considerably. The aim of this study is to evaluate the efficacy of a new Internet-based guided self-help intervention (GET.ON Mood Enhancer) compared to online-based psychoeducation in an investigator-blinded RCT. Methods/design A RCT will be conducted to compare the efficacy of GET.ON Mood Enhancer with an active control condition receiving online psychoeducation on depression (OPD). Both treatment groups will have full access to treatment as usual. Adults with MDD (n = 128) will be recruited and randomised to one of the two conditions. Primary outcome will be observer-rated depressive symptoms (HRSD-24) by independent assessors blind to treatment conditions. Secondary outcomes include changes in self-reported depressive symptom severity, anxiety and quality of life. Additionally, potential negative effects of the treatments will systematically be evaluated on several dimensions (for example, symptom deteriorations, attitudes toward seeking psychological help, relationships and stigmatisation). Assessments will take place at baseline, 6 and 12 weeks after randomisation. Discussion This study evaluates a new Internet-based guided self-help intervention for depression using an active control condition (psychoeducation-control) and an independent, blinded outcome evaluation. This study will further enhance the evidence for Internet-based guided self-help interventions for MDD. Trial registration German Clinical Trial Registration (DRKS): DRKS00005025 PMID:24476555

A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric, Movement and Neurodegenerative Disorders.

PubMed

Lim, Keane; See, Yuen Mei; Lee, Jimmy

2017-11-30

The discovery of endocannabinoid's role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials). A total of 24 reports that evaluated the use of medical cannabis for Alzheimer's disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington's disease, Parkinson's disease, post-traumatic stress disorder (PTSD), psychosis and Tourette syndrome were included in this review. Trial quality was assessed with the Cochrane risk of bias tool. There is a lack of evidence on the therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and dystonia. Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer's disease and dementia, Huntington's disease, and Tourette syndrome, and dyskinesia in Parkinson's disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size. More adequately powered controlled trials that examine the long and short term efficacy, safety and tolerability of cannabis for medical use, and the mechanisms underpinning the therapeutic potential are warranted.

Efficacy of Web-Based Personalized Normative Feedback: A Two-Year Randomized Controlled Trial

ERIC Educational Resources Information Center

Neighbors, Clayton; Lewis, Melissa A.; Atkins, David C.; Jensen, Megan M.; Walter, Theresa; Fossos, Nicole; Lee, Christine M.; Larimer, Mary E.

2010-01-01

Objective: Web-based brief alcohol interventions have the potential to reach a large number of individuals at low cost; however, few controlled evaluations have been conducted to date. The present study was designed to evaluate the efficacy of gender-specific versus gender-nonspecific personalized normative feedback (PNF) with single versus…

Biomarker Evaluation Does Not Confirm Efficacy of Computer-Tailored Nutrition Education

ERIC Educational Resources Information Center

Kroeze, Willemieke; Dagnelie, Pieter C.; Heymans, Martijn W.; Oenema, Anke; Brug, Johannes

2011-01-01

Objective: To evaluate the efficacy of computer-tailored nutrition education with objective outcome measures. Design: A 3-group randomized, controlled trial with posttests at 1 and 6 months post-intervention. Setting: Worksites and 2 neighborhoods in the urban area of Rotterdam. Participants: A convenience sample of healthy Dutch adults (n = 442).…

Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research.

PubMed

Olfson, Mark; Marcus, Steven C

2013-06-01

The Affordable Care Act offers strong support for comparative effectiveness research, which entails comparisons among active treatments, to provide the foundation for evidence-based practice. Traditionally, a key form of research into the effectiveness of therapeutic treatments has been placebo-controlled trials, in which a specified treatment is compared to placebo. These trials feature high-contrast comparisons between treatments. Historical trends in placebo-controlled trials have been evaluated to help guide the comparative effectiveness research agenda. We investigated placebo-controlled trials reported in four leading medical journals between 1966 and 2010. We found that there was a significant decline in average effect size or average difference in efficacy (the ability to produce a desired effect) between the active treatment and placebo. On average, recently studied treatments offered only small benefits in efficacy over placebo. A decline in effect sizes in conventional placebo-controlled trials supports an increased emphasis on other avenues of research, including comparative studies on the safety, tolerability, and cost of treatments with established efficacy.

Psychological Treatment of Depression in People Aged 65 Years and Over: A Systematic Review of Efficacy, Safety, and Cost-Effectiveness

PubMed Central

Jonsson, Ulf; Bertilsson, Göran; Gyllensvärd, Harald; Söderlund, Anne; Tham, Anne; Andersson, Gerhard

2016-01-01

Objectives Depression in elderly people is a major public health concern. As response to antidepressants is often unsatisfactory in this age group, there is a need for evidence-based non-pharmacological treatment options. Our objectives were twofold: firstly, to synthesize published trials evaluating efficacy, safety and cost-effectiveness of psychological treatment of depression in the elderly and secondly, to assess the quality of evidence. Method The electronic databases PubMed, EMBASE, Cochrane Library, CINAL, Scopus, and PsycINFO were searched up to 23 May 2016 for randomized controlled trials (RCTs) of psychological treatment for depressive disorders or depressive symptoms in people aged 65 years and over. Two reviewers independently assessed relevant studies for risk of bias. Where appropriate, the results were synthesized in meta-analyses. The quality of the evidence was graded according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results Twenty-two relevant RCTs were identified, eight of which were excluded from the synthesis due to a high risk of bias. Of the remaining trials, six evaluated problem-solving therapy (PST), five evaluated other forms of cognitive behavioural therapy (CBT), and three evaluated life review/reminiscence therapy. In frail elderly with depressive symptoms, the evidence supported the efficacy of PST, with large but heterogeneous effect sizes compared with treatment as usual. The results for life-review/reminiscence therapy and CBT were also promising, but because of the limited number of trials the quality of evidence was rated as very low. Safety data were not reported in any included trial. The only identified cost-effectiveness study estimated an incremental cost per additional point reduction in Beck Depression Inventory II score for CBT compared with talking control and treatment as usual. Conclusion Psychological treatment is a feasible option for frail elderly with depressive symptoms. However, important questions about efficacy, generalizability, safety and cost-effectiveness remain. PMID:27537217

Vaccines for preventing typhoid fever.

PubMed

Milligan, Rachael; Paul, Mical; Richardson, Marty; Neuberger, Ami

2018-05-31

Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi-TT) conjugate vaccine, Typbar-TCV, as the preferred vaccine for all ages. To assess the effects of vaccines for preventing typhoid fever. In February 2018, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and mRCT. We also searched the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease) in adults and children. Human challenge studies were not eligible. Two review authors independently applied inclusion criteria and extracted data, and assessed the certainty of the evidence using the GRADE approach. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella enterica serovar Typhi in blood. We calculated risk ratios (RRs) and efficacy (1 - RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs contributed to the quantitative analysis in this review: 13 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 6 trials; Vi-rEPA: 1 trial; Vi-TT: 1 trial), and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers. Only one trial included data on children under two years of age.Ty21a vaccine (oral vaccine, three doses)A three-dose schedule of Ty21a vaccine probably prevents around half of typhoid cases during the first three years after vaccination (cumulative efficacy 2.5 to 3 years: 50%, 95% CI 35% to 61%, 4 trials, 235,239 participants, moderate-certainty evidence). These data include patients aged 3 to 44 years.Compared with placebo, this vaccine probably does not cause more vomiting, diarrhoea, nausea or abdominal pain (2 trials, 2066 participants; moderate-certainty evidence), headache, or rash (1 trial, 1190 participants; moderate-certainty evidence); however, fever (2 trials, 2066 participants; moderate-certainty evidence) is probably more common following vaccination.Vi polysaccharide vaccine (injection, one dose)A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (year 1: 69%, 95% CI 63% to 74%; 3 trials, 99,979 participants; high-certainty evidence). In year 2, trial results were more variable, with the vaccine probably preventing between 45% and 69% of typhoid cases (year 2: 59%, 95% CI 45% to 69%; 4 trials, 194,969 participants; moderate-certainty evidence). These data included participants aged 2 to 55 years of age.The three-year cumulative efficacy of the vaccine may be around 55% (95% CI 30% to 70%; 11,384 participants, 1 trial; low-certainty evidence). These data came from a single trial conducted in South Africa in the 1980s in participants aged 5 to 15 years.Compared with placebo, this vaccine probably did not increase the incidence of fever (3 trials, 132,261 participants; moderate-certainty evidence) or erythema (3 trials, 132,261 participants; low-certainty evidence); however, swelling (3 trials, 1767 participants; moderate-certainty evidence) and pain at the injection site (1 trial, 667 participants; moderate-certainty evidence) were more common in the vaccine group.Vi-rEPA vaccine (two doses)Administration of two doses of the Vi-rEPA vaccine probably prevents between 50% and 96% of typhoid cases during the first two years after vaccination (year 1: 94%, 95% CI 75% to 99%; year 2: 87%, 95% CI 56% to 96%, 1 trial, 12,008 participants; moderate-certainty evidence). These data came from a single trial with children two to five years of age conducted in Vietnam.Compared with placebo, both the first and the second dose of this vaccine increased the risk of fever (1 trial, 12,008 and 11,091 participants, low-certainty evidence) and the second dose increase the incidence of swelling at the injection site (one trial, 11,091 participants, moderate-certainty evidence).Vi-TT vaccine (two doses)We are uncertain of the efficacy of administration of two doses of Vi-TT (PedaTyph) in typhoid cases in children during the first year after vaccination (year 1: 94%, 95% CI -1% to 100%, 1 trial, 1625 participants; very low-certainty evidence). These data come from a single cluster-randomized trial in children aged six months to 12 years and conducted in India. For single dose Vi-TT (Typbar-TCV), we found no efficacy trials evaluating the vaccine with natural exposure.There were no reported serious adverse effects in RCTs of any of the vaccines studied. The licensed Ty21a and Vi polysaccharide vaccines are efficacious in adults and children older than two years in endemic countries. The Vi-rEPA vaccine is just as efficacious, although data is only available for children. The new Vi-TT vaccine (PedaTyph) requires further evaluation to determine if it provides protection against typhoid fever. At the time of writing, there were only efficacy data from a human challenge setting in adults on the Vi-TT vaccine (Tybar), which clearly justify the ongoing field trials to evaluate vaccine efficacy.

Structuring Process Evaluation to Forecast Use and Sustainability of an Intervention: Theory and Data From the Efficacy Trial for Lunch Is in the Bag.

PubMed

Roberts-Gray, Cindy; Sweitzer, Sara J; Ranjit, Nalini; Potratz, Christa; Rood, Magdalena; Romo-Palafox, Maria Jose; Byrd-Williams, Courtney E; Briley, Margaret E; Hoelscher, Deanna M

2017-08-01

A cluster-randomized trial at 30 early care and education centers (Intervention = 15, waitlist Control = 15) showed the Lunch Is in the Bag intervention increased parents' packing of fruits, vegetables, and whole grains in their preschool children's bag lunches (parent-child dyads = 351 Intervention, 282 Control). To examine the utility of structuring the trial's process evaluation to forecast use, sustainability, and readiness of the intervention for wider dissemination and implementation. Pretrial, the research team simulated user experience to forecast use of the intervention. Multiattribute evaluation of user experience measured during the trial assessed use and sustainability of the intervention. Thematic analysis of posttrial interviews with users evaluated sustained use and readiness for wider dissemination. Moderate use was forecast by the research team. Multiattribute evaluation of activity logs, surveys, and observations during the trial indicated use consistent with the forecast except that prevalence of parents reading the newsletters was greater (83% vs. 50%) and hearing their children talk about the classroom was less (4% vs. 50%) than forecast. Early care and education center-level likelihood of sustained use was projected to be near zero. Posttrial interviews indicated use was sustained at zero centers. Structuring the efficacy trial's process evaluation as a progression of assessments of user experience produced generally accurate forecasts of use and sustainability of the intervention at the trial sites. This approach can assist interpretation of trial outcomes, aid decisions about dissemination of the intervention, and contribute to translational science for improving health.

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

PubMed

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

2016-10-21

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

Effectiveness of Modular CBT for Child Anxiety in Elementary Schools

ERIC Educational Resources Information Center

Chiu, Angela W.; Langer, David A.; McLeod, Bryce D.; Har, Kim; Drahota, Amy; Galla, Brian M.; Jacobs, Jeffrey; Ifekwunigwe, Muriel; Wood, Jeffrey J.

2013-01-01

Most randomized controlled trials of cognitive-behavioral therapy (CBT) for children with anxiety disorders have evaluated treatment efficacy using recruited samples treated in research settings. Clinical trials in school settings are needed to determine if CBT can be effective when delivered in real world settings. This study evaluated a modular…

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

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

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

Clamp-Crushing versus stapler hepatectomy for transection of the parenchyma in elective hepatic resection (CRUNSH) - A randomized controlled trial (NCT01049607)

PubMed Central

2011-01-01

Background Hepatic resection is still associated with significant morbidity. Although the period of parenchymal transection presents a crucial step during the operation, uncertainty persists regarding the optimal technique of transection. It was the aim of the present randomized controlled trial to evaluate the efficacy and safety of hepatic resection using the technique of stapler hepatectomy compared to the simple clamp-crushing technique. Methods/Design The CRUNSH Trial is a prospective randomized controlled single-center trial with a two-group parallel design. Patients scheduled for elective hepatic resection without extrahepatic resection at the Department of General-, Visceral- and Transplantation Surgery, University of Heidelberg are enrolled into the trial and randomized intraoperatively to hepatic resection by the clamp-crushing technique and stapler hepatectomy, respectively. The primary endpoint is total intraoperative blood loss. A set of general and surgical variables are documented as secondary endpoints. Patients and outcome-assessors are blinded for the treatment intervention. Discussion The CRUNSH Trial is the first randomized controlled trial to evaluate efficacy and safety of stapler hepatectomy compared to the clamp-crushing technique for parenchymal transection during elective hepatic resection. Trial Registration ClinicalTrials.gov: NCT01049607 PMID:21888669

Methodology of phase II clinical trials in metastatic elderly breast cancer: a literature review.

PubMed

Cabarrou, B; Mourey, L; Dalenc, F; Balardy, L; Kanoun, D; Roché, H; Boher, J M; Rougé-Bugat, M E; Filleron, Thomas

2017-08-01

As the incidence of invasive breast cancer will increase with age, the number of elderly patients with a diagnosis metastatic breast cancer will also rise. But the use of cytotoxic drugs in elderly metastatic breast cancer patients is not systematic and is dreaded by medical oncologists. The need for prospective oncologic data from this population seems increasingly obvious. The main objective of this review is to investigate design and characteristics of phase II trials that assess activity and feasibility of chemotherapies in elderly advanced/metastatic breast cancer patients. An electronic search in PUBMED allowed us to retrieve articles published in English language on phase II trials in elderly metastatic breast cancer between January 2002 and May 2016. Sixteen publications were finally included in this review. The primary endpoint was a simple, a composite, and a co-primary endpoints in 11, three, and two studies, respectively. Efficacy was the primary objective in 15 studies: simple (n = 10), composite (n = 3), co-primary endpoints (n = 2). Composite or co-primary endpoints combined efficacy and toxicity. Thirteen studies used multistage designs. Only five studies evaluated the feasibility, i.e., to jointly assess efficacy and tolerance to treatment (toxicity, quality of life, etc) as primary endpoint. Development of elderly specific phase III clinical trials might be challenging, it therefore seems essential to conduct phase II clinical trials evaluating jointly efficacy and toxicity in a well-defined geriatric population. Use of multistage designs that take into account heterogeneity would allow to identify a subpopulation at interim analysis and to reduce the number of patients exposed to an inefficient or a toxic treatment regimen. It is crucial to evaluate new therapies (targeted therapies, immunotherapies) using adequate methodologies (Study design, endpoint).

Field Trial of Attenuated Salmonella Typhi Live Oral Vaccine TY21A in Liquid and Enteric-Coated Formulations and Epidemiological Survey for Incidence of Diarrhea due to Shigella Species

DTIC Science & Technology

1989-03-01

and absolute efficacy of three doses of Ty2la vaccine given in enteric-coated capsule or liquid formulation. Intensive clinical and bacteriologic...TABLES Table 1. Evaluation of the efficacy of three doses of the enteric-coated capsule formulation of Ty2la live oral vaccine given within one week in...November, 1986 thzough February, 1989 of a field trial in Area Sur Oriente and Area Norte assessing the efficacy of Ty21a vaccine in liquid or enteric

Characteristics of antimicrobial studies registered in the USA through ClinicalTrials.Gov

PubMed Central

Stockmann, Chris; Sherwin, Catherine M.T.; Ampofo, Krow; Hersh, Adam L.; Pavia, Andrew T.; Byington, Carrie L.; Ward, Robert M.; Spigarelli, Michael G.

2013-01-01

Increasing rates of antimicrobial-resistant infections and the dwindling pipeline of new agents necessitate judicious, evidence-based antimicrobial prescribing. Clinical trials represent a vital resource for establishing evidence of safety and efficacy, which are crucial to guiding antimicrobial treatment decisions. The objective of this study was to comprehensively evaluate the characteristics of antimicrobial research studies registered in ClinicalTrials.gov. Primary outcome measures, funding sources, inclusion criteria and the reporting of study results were evaluated for 16 055 antimicrobial studies registered in ClinicalTrials.gov as of mid 2012. Interventional studies accounted for 93% of registered antimicrobial studies. Clinical trials of drugs (82%) and biologics (9%) were most common. Antibacterial, antiviral and antifungal studies accounted for 43%, 41% and 16% of drug trials, respectively. Among interventional drug trials, 73% featured randomised allocation to study arms and 71% included measures of safety and/or efficacy as primary endpoints. Children were eligible for enrolment in 26% of studies. Among the studies, 60% were sponsored primarily by non-profit organisations, 30% by industry and 10% by the federal government. Only 7% of studies reported results; however, 71% of these were sponsored primarily by industry. Antimicrobial studies commonly incorporated elements of high-quality trial design, including randomisation and safety/efficacy endpoints. Publication of study results and updating of ClinicalTrials.gov should be encouraged for all studies, with particular attention paid to research sponsored by non-profit organisations and governmental agencies. Leveraging the application of these data to guide the careful selection of antimicrobial agents will be essential to preserve their utility for years to come. PMID:23726436

The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets. Methods/design This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy. Discussion This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial. Trial registration This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197. PMID:24359521

The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study

PubMed Central

Shi, Yuankai; Zhou, Caicun; Liu, Xiaoqing; Wang, Dong; Song, Yong; Li, Qiang; Feng, Jifeng; Qin, Shukui; Xv, Nong; Zhou, Jianying; Zhang, Li; Hu, Chunhong; Zhang, Shucai; Luo, Rongcheng; Wang, Jie; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2015-01-01

Background Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Methods Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. Results From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9–6.6 m) and 5.4 months (95%CI 3.1–7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). Conclusions In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. Trial Registration ClinicalTrials.gov NCT02486354 PMID:26599904

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

PubMed Central

2013-01-01

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

Efficacy of electroacupuncture for symptoms of menopausal transition: study protocol for a randomized controlled trial.

PubMed

Liu, Zhishun; Wang, Yang; Xu, Huanfang; Wu, Jiani; He, Liyun; Jiang, John Yi; Yan, Shiyan; Du, Ruosang; Liu, Baoyan

2014-06-21

Previous studies have shown that acupuncture can alleviate postmenopausal symptoms, such as hot flashes, but few studies have assessed symptoms during the menopausal transition (MT) period. Thus, the effect of acupuncture upon MT symptoms is unclear. We designed a large-scale trial aimed at evaluating the efficacy of electroacupuncture for MT symptoms compared with sham electroacupuncture and at observing the safety of electroacupuncture. In this multicenter randomized controlled trial, 360 women will be randomized to either an electroacupuncture group or a sham electroacupuncture group. During the 8-week-long treatment, a menopause rating scale, average 24-hour hot flash score, Menopause-Specific Quality of Life Questionnaire score, and level of female hormones will be observed. Follow-ups at the 20th and 32nd week will be made. Though there is no completely inert placebo acupuncture and blinding is difficult in acupuncture trials, the placebo effect of EA can still be partially excluded in this study. For the placebo control, we use non-points and a tailor-made sham needle. This needle is different from a retractable needle, which is usually used for sham acupuncture. The needle in this trial is more simply constructed and more acceptable to Chinese people. We expect to evaluate the efficacy of electroacupuncture for MT symptoms and clarify its effect on these symptoms. ClinicalTrials.gov Identifier: NCT01849172 (Date of registration: 05/05/2013).

Evaluating the Dissemination of "Body & Soul," an Evidence-based Fruit and Vegetable Intake Intervention: Challenges for Dissemination and Implementation Research

ERIC Educational Resources Information Center

Allicock, Marlyn; Campbell, Marci K.; Valle, Carmina G.; Carr, Carol; Resnicow, Ken; Gizlice, Ziya

2012-01-01

Objective: To evaluate whether the evidence-based "Body & Soul" program, when disseminated and implemented without researcher or agency involvement and support, would achieve results similar to those of earlier efficacy and effectiveness trials. Design: Prospective group randomized trial. Setting: Churches with predominantly African American…

A call for more transparency of registered clinical trials on endometriosis

PubMed Central

Guo, Sun-Wei; Hummelshoj, Lone; Olive, David L.; Bulun, Serdar E.; D'Hooghe, Thomas M.; Evers, Johannes L.H.

2009-01-01

In response to the pressing need for more efficacious and safer therapeutics for endometriosis, there have been numerous reports in the last decade of positive results from animal and in vitro studies of various compounds as potential therapeutics for endometriosis. A handful of these have undergone phase II/III clinical trials. Since the announcement of the International Committee of Medical Journal Editors that mandated registration as a prerequisite for publication, 57 endometriosis-related clinical trials have been registered at ClinicalTrials.gov, an Internet-based public depository for information on drug studies. Among them, 25 are listed as completed, and 2 as suspended. There are 15 completed phase II/III trials, which evaluated the efficacy of various promising compounds. Yet only three of the 15 trials (20%) have published their results. The remaining 12 (80%) studies so far have not published their findings. We argue that this apparent lack of transparency will actually not benefit the trial sponsors or the public, and will ultimately prove detrimental to research efforts attempting to develop more efficacious and safer therapeutics for endometriosis. Thus we call for more transparency of clinical trials on endometriosis. PMID:19264712

The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola.

PubMed

2015-07-27

A World Health Organization expert meeting on Ebola vaccines proposed urgent safety and efficacy studies in response to the outbreak in West Africa. One approach to communicable disease control is ring vaccination of individuals at high risk of infection due to their social or geographical connection to a known case. This paper describes the protocol for a novel cluster randomised controlled trial design which uses ring vaccination.In the Ebola ça suffit ring vaccination trial, rings are randomised 1:1 to (a) immediate vaccination of eligible adults with single dose vaccination or (b) vaccination delayed by 21 days. Vaccine efficacy against disease is assessed in participants over equivalent periods from the day of randomisation. Secondary objectives include vaccine effectiveness at the level of the ring, and incidence of serious adverse events. Ring vaccination trials are adaptive, can be run until disease elimination, allow interim analysis, and can go dormant during inter-epidemic periods. © Ebola ça suffit ring vaccination trial consortium 2015.

Programs for the Prevention of Youth Depression: Evaluation of Efficacy, Effectiveness, and Readiness for Dissemination

PubMed Central

Brunwasser, Steven M.; Garber, Judy

2015-01-01

Objective To evaluate the current state of evidence of the effectiveness of depression prevention programs for youth, assess the degree to which current evidence supports broad implementation, and outline additional steps needed to close the gap between effectiveness and dissemination. Method We used the Society for Prevention Research’s Standards of Evidence (Flay et al., 2005) to evaluate the degree to which existing depression prevention programs have established intervention efficacy, effectiveness, and readiness for dissemination. We reviewed all depression prevention programs for youth that have been evaluated in at least two published, randomized controlled trials in which the intervention was compared to a no-intervention control group. A total of 37 studies evaluating 11 different programs were reviewed with regard to depressive symptoms and diagnoses post intervention and at follow-up (at least 6 months). Results Eight programs demonstrated significant main effects on depressive symptoms relative to controls in multiple RCTs; five programs had at least one trial with significant main effects present at least one year post-intervention. Two programs demonstrated efficacy for both depressive symptoms and depressive episodes across multiple independent trials. Regarding effectiveness, six programs had at least one study showing significant effects when delivered by endogenous service providers; four programs had significant effects in studies conducted independently of the program developers. Conclusions Several programs have demonstrated promise in terms of efficacy, but no depression prevention program for children or adolescents as yet has garnered sufficient evidence of effectiveness under real-world conditions to warrant widespread dissemination at this time. PMID:25933173

Accounting for interim safety monitoring of an adverse event upon termination of a clinical trial.

PubMed

Dallas, Michael J

2008-01-01

Upon termination of a clinical trial that uses interim evaluations to determine whether the trial can be stopped, a proper statistical analysis must account for the interim evaluations. For example, in a group-sequential design where the efficacy of a treatment regimen is evaluated at interim stages, and the opportunity to stop the trial based on positive efficacy findings exists, the terminal p-value, point estimate, and confidence limits of the outcome of interest must be adjusted to eliminate bias. While it is standard practice to adjust terminal statistical analyses due to opportunities to stop for "positive" findings, adjusting due to opportunities to stop for "negative" findings is also important. Stopping rules for negative findings are particularly useful when monitoring a specific rare serious adverse event in trials designed to show safety with respect to the event. In these settings, establishing conservative stopping rules are appropriate, and therefore accounting for the interim monitoring can have a substantial effect on the final results. Here I present a method to account for interim safety monitoring and illustrate its usefulness. The method is demonstrated to have advantages over methodology that does not account for interim monitoring.

The efficacy of systemic therapy for internalizing and other disorders of childhood and adolescence: a systematic review of 38 randomized trials.

PubMed

Retzlaff, Ruediger; von Sydow, Kirsten; Beher, Stefan; Haun, Markus W; Schweitzer, Jochen

2013-12-01

Systemic therapy (ST) is one of the most widely applied psychotherapeutic approaches in the treatment of children and adolescents, yet few systematic reviews exist on the efficacy of ST with this age group. Parallel to a similar study on adults, a systematic review was performed to analyze the efficacy of ST in the treatment of children and adolescents. All randomized or matched controlled trials (RCT) evaluating ST in any setting with child and adolescent index patients were identified by database searches and cross-references, as well as in existing meta-analyses and reviews. Inclusion criteria were: index patient diagnosed with a DSM-IV or ICD-10 listed psychological disorder, or suffering from other clinically relevant conditions, and trial published by December 2011. Studies were analyzed according to their sample, research methodology, interventions applied, and results at end-of-treatment and at follow-up. This article presents findings for internalizing and mixed disorders. Thirty-eight trials were identified, with 33 showing ST to be efficacious for the treatment of internalizing disorders (including mood disorders, eating disorders, and psychological factors in somatic illness). There is some evidence for ST being also efficacious in mixed disorders, anxiety disorders, Asperger disorder, and in cases of child neglect. Results were stable across follow-up periods of up to 5 years. Trials on the efficacy of ST for externalizing disorders are presented in a second article. There is a sound evidence base for the efficacy of ST as a treatment for internalizing disorders of child and adolescent patients. © FPI, Inc.

The Efficacy and Safety of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Previously Treated with Chemotherapy: A Single-Arm, Multi-Center, Prospective Study.

PubMed

Hu, Xingsheng; Zhang, Li; Shi, Yuankai; Zhou, Caicun; Liu, Xiaoqing; Wang, Dong; Song, Yong; Li, Qiang; Feng, Jifeng; Qin, Shukui; Xv, Nong; Zhou, Jianying; Zhang, Li; Hu, Chunhong; Zhang, Shucai; Luo, Rongcheng; Wang, Jie; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2015-01-01

Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125 mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9-6.6 m) and 5.4 months (95%CI 3.1-7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. ClinicalTrials.gov NCT02486354.

Efficacy, Tolerability, and Dose-Dependent Effects of Opioid Analgesics for Low Back Pain: A Systematic Review and Meta-analysis.

PubMed

Abdel Shaheed, Christina; Maher, Chris G; Williams, Kylie A; Day, Richard; McLachlan, Andrew J

2016-07-01

Opioid analgesics are commonly used for low back pain, however, to our knowledge there has been no systematic evaluation of the effect of opioid dose and use of enrichment study design on estimates of treatment effect. To evaluate efficacy and tolerability of opioids in the management of back pain; and investigate the effect of opioid dose and use of an enrichment study design on treatment effect. Medline, EMBASE, CENTRAL, CINAHL, and PsycINFO (inception to September 2015) with citation tracking from eligible randomized clinical trials (RCTs). Placebo-controlled RCTs in any language. Two authors independently extracted data and assessed risk of bias. Data were pooled using a random effects model with strength of evidence assessed using the grading of recommendations assessment, development, and evaluation (GRADE). The primary outcome measure was pain. Pain and disability outcomes were converted to a common 0 to 100 scale, with effects greater than 20 points considered clinically important. Of 20 included RCTs of opioid analgesics (with a total of 7925 participants), 13 trials (3419 participants) evaluated short-term effects on chronic low back pain, and no placebo-controlled trials enrolled patients with acute low back pain. In half of these 13 trials, at least 50% of participants withdrew owing to adverse events or lack of efficacy. There was moderate-quality evidence that opioid analgesics reduce pain in the short term; mean difference (MD), -10.1 (95% CI, -12.8 to -7.4). Meta-regression revealed a 12.0 point greater pain relief for every 1 log unit increase in morphine equivalent dose (P = .046). Clinically important pain relief was not observed within the dose range evaluated (40.0-240.0-mg morphine equivalents per day). There was no significant effect of enrichment study design. For people with chronic low back pain who tolerate the medicine, opioid analgesics provide modest short-term pain relief but the effect is not likely to be clinically important within guideline recommended doses. Evidence on long-term efficacy is lacking. The efficacy of opioid analgesics in acute low back pain is unknown.

Safety and efficacy of endovascular therapy and gamma knife surgery for brain arteriovenous malformations in China: Study protocol for an observational clinical trial.

PubMed

Jin, Hengwei; Huo, Xiaochuan; Jiang, Yuhua; Li, Xiaolong; Li, Youxiang

2017-09-01

Brain arteriovenous malformations (BAVMs) are associated with high morbidity and mortality. The treatment of BAVM remains controversial. Microinvasive treatment, including endovascular therapy and gamma knife surgery, has been the first choice in many conditions. However, the overall clinical outcome of microinvasive treatment remains unknown and a prospective trial is needed. This is a prospective, non-randomized, and multicenter observational registry clinical trial to evaluate the safety and efficacy of microinvasive treatment for BAVMs. The study will require up to 400 patients in approximately 12 or more centers in China, followed for 2 years. Main subjects of this study are BAVM patients underwent endovascular therapy and/or gamma knife surgery. The trial will not affect the choice of treatment modality. The primary outcomes are perioperative complications (safety), and postoperative hemorrhage incidence rate and complete occlusion rate (efficacy). Secondary outcomes are elimination of hemorrhage risk factors (coexisting aneurysms and arteriovenous fistula), volume reduction and remission of symptoms. Safety and efficacy of endovascular therapy, gamma knife surgery, and various combination modes of the two modalities will be compared. Operative complications and outcomes at pretreatment, post-treatment, at discharge and at 3 months, 6 months and 2 years follow-up intervals will be analyzed using the modified Rankin Scale (mRS). The most confusion on BAVM treatment is whether to choose interventional therapy or medical therapy, and the choice of interventional therapy modes. This study will provide evidence for evaluating the safety and efficacy of microinvasive treatment in China, to characterize the microinvasive treatment strategy for BAVMs.

Pediatric obesity pharmacotherapy: current state of the field, review of the literature and clinical trial considerations.

PubMed

Kelly, A S; Fox, C K; Rudser, K D; Gross, A C; Ryder, J R

2016-07-01

Despite the increasing number of medications recently approved to treat obesity among adults, few agents have been formally evaluated in children or adolescents for this indication. Moreover, there is a paucity of guidance in the literature addressing best practices with regard to pediatric obesity pharmacotherapy clinical trial design, and only general recommendations have been offered by regulatory agencies on this topic. The purposes of this article are to (1) offer a background of the current state of the field of pediatric obesity medicine, (2) provide a brief review of the literature summarizing pediatric obesity pharmacotherapy clinical trials, and (3) highlight and discuss some of the unique aspects that should be considered when designing and conducting high-quality clinical trials evaluating the safety and efficacy of obesity medications in children and adolescents. Suggestions are offered in the areas of target population and eligibility criteria, clinical trial end-point selection, trial duration, implementation of lifestyle modification therapy and recruitment and retention of participants. Efforts should be made to design and conduct trials appropriately to ensure that high-quality evidence is generated on the safety and efficacy of various medications used to treat pediatric obesity.

Pediatric Obesity Pharmacotherapy: Current State of the Field, Review of the Literature, and Clinical Trial Considerations

PubMed Central

Kelly, Aaron S.; Fox, Claudia K.; Rudser, Kyle D.; Gross, Amy C.; Ryder, Justin R.

2017-01-01

Despite the increasing number of medications recently approved to treat obesity among adults, few agents have been formally evaluated in children or adolescents for this indication. Moreover, there is a paucity of guidance in the literature addressing best practices in regard to pediatric obesity pharmacotherapy clinical trial design, and only general recommendations have been offered by regulatory agencies on this topic. The purposes of this article are to: 1) offer a background of the current state of the field of pediatric obesity medicine; 2) provide a brief review of the literature summarizing pediatric obesity pharmacotherapy clinical trials; and 3) highlight and discuss some of the unique aspects that should be considered when designing and conducting high-quality clinical trials evaluating the safety and efficacy of obesity medications in children and adolescents. Suggestions are offered in the areas of target population and eligibility criteria, clinical trial endpoint selection, trial duration, implementation of lifestyle modification therapy, and recruitment and retention of participants. Efforts should be made to design and conduct trials appropriately to ensure that high-quality evidence is generated on the safety and efficacy of various medications used to treat pediatric obesity. PMID:27113643

Feasibility of Conducting a Randomized Trial to Promote Healthy Eating, Active Play and Sustainability Awareness in Early Childhood Curricula

ERIC Educational Resources Information Center

Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie Margaret; Cutter-Mackenzie, Amy; O'Connor, Amanda; Mantilla, Ana; Huang, Terry TK; Lording, Kate Marion; Williams-Smith, Janet

2016-01-01

We sought to evaluate the feasibility of conducting a randomized trial to evaluate the efficacy of a preschool/kindergarten curriculum intervention designed to increase 4-year-old children's knowledge of healthy eating, active play and the sustainability consequences of their food and toy choices. Ninety intervention and 65 control parent/child…

Control of Scaphoideus titanus with Natural Products in Organic Vineyards

PubMed Central

Tacoli, Federico; Mori, Nicola; Cargnus, Elena; Da Vià, Sarah; Zandigiacomo, Pietro; Duso, Carlo; Pavan, Francesco

2017-01-01

The leafhopper Scaphoideus titanus is the vector of ‘Candidatus Phytoplasma vitis’, the causal agent of Flavescence dorée (FD) a key disease for European viticulture. In organic vineyards, the control of S. titanus relies mostly on the use of pyrethrins that have suboptimal efficacy. During 2016, three field trials were conducted to evaluate the efficacy of kaolin, orange oil, insecticidal soap and spinosad against S. titanus nymphs, in comparison with pyrethrins. The activity of kaolin was evaluated also in the laboratory. In all field trials, kaolin had an efficacy against nymphs comparable to pyrethrins, while the other products were not effective. Laboratory results confirmed that kaolin increased nymph mortality. In organic vineyards, kaolin and pyrethrins are valuable tools in the management of FD. Nevertheless, their efficacy is lower compared to that of the synthetic insecticides used in conventional viticulture. Therefore, further research should be conducted in order to identify alternatives to synthetic insecticides for S. titanus control in the context of organic viticulture. PMID:29258165

Oral Antibacterial Therapy for Acne Vulgaris: An Evidence-Based Review.

PubMed

Bienenfeld, Amanda; Nagler, Arielle R; Orlow, Seth J

2017-08-01

To some degree, acne vulgaris affects nearly every individual worldwide. Oral antibiotic therapy is routinely prescribed for the treatment of moderate to severe inflammatory acne; however, long-term use of oral antibiotics for acne may have unintended consequences. The aim of this study was to provide a systematic evaluation of the scientific evidence on the efficacy and appropriate use of oral antibiotics in the treatment of acne. A systematic search of MEDLINE was conducted to identify randomized controlled clinical trials, systematic reviews, and meta-analyses evaluating the efficacy of oral antibiotics for acne. Overall, 41 articles that examined oral antibiotics compared with placebo, another oral therapy, topical therapy, alternate dose, or duration were included in this study. Tetracyclines, macrolides, and trimethoprim/sulfamethoxazole are effective and safe in the treatment of moderate to severe inflammatory acne. Superior efficacy of one type or class of antibiotic could not be determined, therefore the choice of antibiotic is generally based on the side-effect profile. Although different dosing regimens have been studied, there is a lack of standardized comparator trials to determine optimal dosing and duration of each oral antibiotic used in acne. The combination of oral antibiotics with a topical therapy is superior to oral antibiotics alone. This article provides a systematic evaluation of the scientific evidence of the efficacy of oral antibiotics for acne. Due to heterogeneity in the design of the trials, there is insufficient evidence to support one type, dose, or duration of oral antibiotic over another in terms of efficacy; however, due to increasing resistance to antibiotics, dermatologists should heed consensus guidelines for their appropriate use.

Design of a phase III multicenter trial to evaluate the efficacy of the RTS,S/AS01 malaria vaccine in children across diverse transmission settings in Africa

PubMed Central

2011-01-01

Background GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative are working in partnership to develop a malaria vaccine to protect infants and children living in malaria endemic regions of sub-Saharan Africa, which can be delivered through the Expanded Programme on Immunization. The RTS,S/AS candidate vaccine has been evaluated in multiple phase I/II studies and shown to have a favourable safety profile and to be well-tolerated in both adults and children. This paper details the design of the phase III multicentre efficacy trial of the RTS,S/AS01 malaria vaccine candidate, which is pivotal for licensure and policy decision-making. Methods The phase III trial is a randomized, controlled, multicentre, participant- and observer-blind study on-going in 11 centres associated with different malaria transmission settings in seven countries in sub-Saharan Africa. A minimum of 6,000 children in each of two age categories (6-12 weeks, 5-17 months) have been enrolled. Children were randomized 1:1:1 to one of three study groups: (1) primary vaccination with RTS,S/AS01 and booster dose of RTS,S/AS01; (2) primary vaccination with RTS,S/AS01 and a control vaccine at time of booster; (3) primary vaccination with control vaccine and a control vaccine at time of booster. Primary vaccination comprises three doses at monthly intervals; the booster dose is administered at 18 months post-primary course. Subjects will be followed to study month 32. The co-primary objectives are the evaluation of efficacy over one year post-dose 3 against clinical malaria when primary immunization is delivered at: (1) 6-12 weeks of age, with co-administration of DTPwHepB/Hib antigens and OPV; (2) 5-17 months of age. Secondary objectives include evaluation of vaccine efficacy against severe malaria, anaemia, malaria hospitalization, fatal malaria, all-cause mortality and other serious illnesses including sepsis and pneumonia. Efficacy of the vaccine against clinical malaria under different transmission settings, the evolution of efficacy over time and the potential benefit of a booster will be evaluated. In addition, the effect of RTS,S/AS01 vaccination on growth, and the safety and immunogenicity in HIV-infected and malnourished children will be assessed. Safety of the primary course of immunization and the booster dose will be documented in both age categories. Conclusions This pivotal phase III study of the RTS,S/AS01 candidate malaria vaccine in African children was designed and implemented by the Clinical Trials Partnership Committee. The study will provide efficacy and safety data to fulfil regulatory requirements, together with data on a broad range of endpoints that will facilitate the evaluation of the public health impact of the vaccine and will aid policy and implementation decisions. Trial registration Clinicaltrials.gov NCT00866619 PMID:21816029

Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial

PubMed Central

Wasunna, Monique; Njenga, Simon; Balasegaram, Manica; Alexander, Neal; Omollo, Raymond; Edwards, Tansy; Dorlo, Thomas P. C.; Musa, Brima; Ali, Mohammed Hassan Sharaf; Elamin, Mohammed Yasein; Kirigi, George; Kip, Anke E.; Schoone, Gerard J.; Hailu, Asrat; Olobo, Joseph; Ellis, Sally; Kimutai, Robert; Wells, Susan; Khalil, Eltahir Awad Gasim; Strub Wourgaft, Nathalie; Alves, Fabiana; Musa, Ahmed

2016-01-01

Background SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. Methods A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. Results In sequential analyses with 49–51 patients per arm, initial cure was 85% (95% CI: 73–92) in all arms. At D210, definitive cure was 87% (95% CI: 77–97) for AmBisome + SSG, 77% (95% CI 64–90) for AmBisome + miltefosine and 72% (95% CI 60–85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. Conclusion No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. Trial Registration The study was registered with ClinicalTrials.gov, number NCT01067443 PMID:27627654

What is the role of combination drug therapy in the treatment of overactive bladder? ICI-RS 2014.

PubMed

Visco, Anthony G; Fraser, Matthew O; Newgreen, Donald; Oelke, Matthias; Cardozo, Linda

2016-02-01

The role of combination therapy using oral antimuscarinic medications for the treatment of overactive bladder was proposed at the 2014 International Consultation on Incontinence-Research Society in Bristol, UK to identify key factors to consider when making clinical decisions and to guide future research design. Combination therapy is justified if monotherapy is associated with suboptimal efficacy or bothersome side effects. Combination therapy has the potential to improve efficacy with fewer side effects than monotherapy. Two Phase 2 studies comparing combination therapy that included an antimuscarinic demonstrated improvement in mean voided volume, the primary outcome chosen, with some combinations showing improved micturition frequency and quality of life. The two studies found no evidence of an increased safety risk with combination therapy compared to monotherapy. Future studies should use clinically meaningful or patient reported outcomes such as incontinence episodes when comparing efficacy. If surrogate measures are used, a clear justification should be provided. Cost analyses should be planned for clinical research trials evaluating combination drug therapy. Combination therapy is reasonable when monotherapy has suboptimal efficacy or bothersome side effects. Future research studies evaluating combination therapy for urgency urinary incontinence should ideally(1) be performed as part of a randomized clinical trial,(2) evaluate non-responders to monotherapy,(3) evaluate combination therapy using medications with different mechanisms of action,(4) include clinically meaningful and patient reported outcomes when evaluating efficacy, and(5) include cost-effectiveness analyses to justify any increased cost by showing improvement in efficacy or reduction in side effects. © 2016 Wiley Periodicals, Inc.

Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea.

PubMed

Ahmed, Tanvir; Bhuiyan, Taufiqur R; Zaman, K; Sinclair, David; Qadri, Firdausi

2013-07-05

Infection with enterotoxigenic Escherichia coli (ETEC) bacteria is a common cause of diarrhoea in adults and children in developing countries and is a major cause of 'travellers' diarrhoea' in people visiting or returning from endemic regions. A killed whole cell vaccine (Dukoral®), primarily designed and licensed to prevent cholera, has been recommended by some groups to prevent travellers' diarrhoea in people visiting endemic regions. This vaccine contains a recombinant B subunit of the cholera toxin that is antigenically similar to the heat labile toxin of ETEC. This review aims to evaluate the clinical efficacy of this vaccine and other vaccines designed specifically to protect people against diarrhoea caused by ETEC infection. To evaluate the efficacy, safety, and immunogenicity of vaccines for preventing ETEC diarrhoea. We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and http://clinicaltrials.gov up to December 2012. Randomized controlled trials (RCTs) and quasi-RCTs comparing use of vaccines to prevent ETEC with use of no intervention, a control vaccine (either an inert vaccine or a vaccine normally given to prevent an unrelated infection), an alternative ETEC vaccine, or a different dose or schedule of the same ETEC vaccine in healthy adults and children living in endemic regions, intending to travel to endemic regions, or volunteering to receive an artificial challenge of ETEC bacteria. Two authors independently assessed each trial for eligibility and risk of bias. Two independent reviewers extracted data from the included studies and analyzed the data using Review Manager (RevMan) software. We reported outcomes as risk ratios (RR) with 95% confidence intervals (CI). We assessed the quality of the evidence using the GRADE approach. Twenty-four RCTs, including 53,247 participants, met the inclusion criteria. Four studies assessed the protective efficacy of oral cholera vaccines when used to prevent diarrhoea due to ETEC and seven studies assessed the protective efficacy of ETEC-specific vaccines. Of these 11 studies, seven studies presented efficacy data from field trials and four studies presented efficacy data from artificial challenge studies. An additional 13 trials contributed safety and immunological data only. Cholera vaccinesThe currently available, oral cholera killed whole cell vaccine (Dukoral®) was evaluated for protection of people against 'travellers' diarrhoea' in a single RCT in people arriving in Mexico from the USA. We did not identify any statistically significant effects on ETEC diarrhoea or all-cause diarrhoea (one trial, 502 participants, low quality evidence).Two earlier trials, one undertaken in an endemic population in Bangladesh and one undertaken in people travelling from Finland to Morocco, evaluated a precursor of this vaccine containing purified cholera toxin B subunit rather than the recombinant subunit in Dukoral®. Short term protective efficacy against ETEC diarrhoea was demonstrated, lasting for around three months (RR 0.43, 95% CI 0.26 to 0.71; two trials, 50,227 participants). This vaccine is no longer available. ETEC vaccinesAn ETEC-specific, killed whole cell vaccine, which also contains the recombinant cholera toxin B-subunit, was evaluated in people travelling from the USA to Mexico or Guatemala, and from Austria to Latin America, Africa, or Asia. We did not identify any statistically significant differences in ETEC-specific diarrhoea or all-cause diarrhoea (two trials, 799 participants), and the vaccine was associated with increased vomiting (RR 2.0, 95% CI 1.16 to 3.45; nine trials, 1528 participants). The other ETEC-specific vaccines in development have not yet demonstrated clinically important benefits. There is currently insufficient evidence from RCTs to support the use of the oral cholera vaccine Dukoral® for protecting travellers against ETEC diarrhoea. Further research is needed to develop safe and effective vaccines to provide both short and long-term protection against ETEC diarrhoea.

Evaluating Adaptation of a Cancer Clinical Trial Decision Aid for Rural Cancer Patients: A Mixed-Methods Approach.

PubMed

Pathak, Swati; George, Nerissa; Monti, Denise; Robinson, Kathy; Politi, Mary C

2018-06-03

Rural-residing cancer patients often do not participate in clinical trials. Many patients misunderstand cancer clinical trials and their rights as participant. The purpose of this study is to modify a previously developed cancer clinical trials decision aid (DA), incorporating the unique needs of rural populations, and test its impact on knowledge and decision outcomes. The study was conducted in two phases. Phase I recruited 15 rural-residing cancer survivors in a qualitative usability study. Participants navigated the original DA and provided feedback regarding usability and implementation in rural settings. Phase II recruited 31 newly diagnosed rural-residing cancer patients. Patients completed a survey before and after using the revised DA, R-CHOICES. Primary outcomes included decisional conflict, decision self-efficacy, knowledge, communication self-efficacy, and attitudes towards and willingness to consider joining a trial. In phase I, the DA was viewed positively by rural-residing cancer survivors. Participants provided important feedback about factors rural-residing patients consider when thinking about trial participation. In phase II, after using R-CHOICES, participants had higher certainty about their choice (mean post-test = 3.10 vs. pre-test = 2.67; P = 0.025) and higher trial knowledge (mean percentage correct at post-test = 73.58 vs. pre-test = 57.77; P < 0.001). There was no significant change in decision self-efficacy, communication self-efficacy, and attitudes towards or willingness to join trials. The R-CHOICES improved rural-residing patients' knowledge of cancer clinical trials and reduced conflict about making a trial decision. More research is needed on ways to further support decisions about trial participation among this population.

Enhancing first-time parents' self-efficacy: A systematic review and meta-analysis of universal parent education interventions' efficacy.

PubMed

Liyana Amin, Nur Arina; Tam, Wilson W S; Shorey, Shefaly

2018-06-01

Poor adjustment during early parenthood often leads to low feelings of parental self-efficacy, which influences parents' behaviours towards their infants. The long-term consequences on infant development warrant the need for more attention on the efficacy of universal parent education interventions to empower parents and enhance their self-efficacy. To synthesise available evidence and explore the efficacy of universal parent education interventions on the parental self-efficacy of first-time parents. A systematic review and meta-analysis of randomised controlled trials. A literature search of 10 databases was conducted to identify randomised controlled trials from each database's point of inception to November 2016. Based on the inclusion criteria, 24,062 articles were screened for their titles and abstracts. Two hundred and eighty articles were identified for full-text screening. Risks of bias posed by the selected articles were assessed using Cochrane's Risk of Bias instrument. Meta-analyses were conducted using RevMan 5.3. The overall intervention effect was evaluated using z tests at p < 0.05, while I 2 and Cochran Q tests were used to measure heterogeneity. Ten randomised controlled trials were selected; eight trials were combined in meta-analyses and two trials were synthesised narratively. A meta-analysis revealed that universal parent education interventions significantly enhanced parental self-efficacy (p < 0.001) among first-time parents and these effects were also maintained over time (p < 0.001). The extent of improvement in parental self-efficacy was affected by the duration of the interventions. This review provides sufficient evidence to support the use of universal interventions to enhance new parents' self-efficacy. While intervention effects were sustained at the two-month follow-up, further research using randomised controlled trials and longitudinal studies are needed to determine long-term effects. The findings serve as an impetus for hospitals and healthcare professionals to integrate universal interventions in perinatal care to guide first-time parents' transition into parenthood. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical efficacy of composite versus ceramic inlays and onlays: a systematic review.

PubMed

Fron Chabouis, Hélène; Smail Faugeron, Violaine; Attal, Jean-Pierre

2013-12-01

Large tooth substance losses are frequent in posterior teeth because of primary caries or aging restorations. Inlays and onlays are often the minimal invasive solution in such cases, but the efficacy of the composite and ceramic materials used is unknown. We performed a systematic review of randomized controlled trials comparing the efficacy of composite and ceramic inlays or onlays. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched without any restriction on date or language, as were references of eligible studies and ClinicalTrials.gov. Eligible studies were randomized trials comparing the clinical efficacy of composite to ceramic inlays or onlays in adults with any clinical outcome for at least 6 months. From 172 records identified, we examined reports of 2 randomized controlled trials involving 138 inlays (no onlays evaluated) in 80 patients and exhibiting a high-risk of bias. Outcomes were clinical scores and major failures. The 3-year overall failure risk ratio was 2 [0.38-10.55] in favor of ceramic inlays although not statistically significant. The reported clinical scores (United States Public Health Services and Californian Dental Association) showed considerable heterogeneity between trials and could not be combined. We have very limited evidence that ceramics perform better than composite material for inlays in the short term. However, this result may not be valid in the long term, and other trials are needed. Trials should follow Fédération dentaire internationale recommendations and enhance their methodology. Trials comparing composite and ceramic onlays are needed. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Dietary interventions, lifestyle changes, and dietary supplements in preventing gestational diabetes mellitus: a literature review.

PubMed

Facchinetti, Fabio; Dante, Giulia; Petrella, Elisabetta; Neri, Isabella

2014-11-01

Gestational diabetes mellitus (GDM) is associated with increased rates of fetal morbidity and mortality, both during the pregnancy and in the postnatal life. Current treatment of GDM includes diet with or without medications, but this management is expensive and poorly cost-effective for the health care systems. Strategies to prevent such condition would be preferable with respect to its treatment. The aim of this literature review was to evaluate studies reporting the efficacy of the most used approaches to prevent GDM as well as evidences of efficacy and safety of dietary supplementations. Systematic literature searches were performed in electronic databases, covering the period January 1983 to April 2014. Randomized controlled clinical trials were included. Quality of the articles was evaluated with the Jadad scale. We did not evaluate those articles that were already entered in the most recent systematic reviews, and we completed the research with the trials published thereafter. Of 55 articles identified, 15 randomized controlled trials were eligible. Quality and heterogeneity of the studies cannot allow firm conclusions. Anyway, trials in which only intake or expenditure has been targeted mostly reported negative results. On the contrary, combined lifestyle programs including diet control (orienting food intake, restricting energy intake) associated with moderate but continuous physical activity exhibit better efficacy in reducing GDM prevalence. The results from dietary supplements with myoinositol or probiotics are promising. The actual evidences provide enough arguments for implementing large-scale, high-quality randomized controlled trials looking at the possible benefits of these new approaches for preventing GDM.

First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial.

PubMed

Grønhøj, Christian; Jensen, David H; Glovinski, Peter V; Jensen, Siri Beier; Bardow, Allan; Oliveri, Roberto S; Specht, Lena; Thomsen, Carsten; Darkner, Sune; Kiss, Katalin; Fischer-Nielsen, Anne; von Buchwald, Christian

2017-03-07

Salivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia. This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention. The trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials. EudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015. ClinicalTrials.gov, Identifier: NCT02513238 . First received on 2 July 2015. The trial is prospectively registered.

Efficacy and Safety of ATX-101 by Treatment Session: Pooled Analysis of Data from the Phase 3 REFINE Trials.

PubMed

Dayan, Steven H; Schlessinger, Joel; Beer, Kenneth; Donofrio, Lisa M; Jones, Derek H; Humphrey, Shannon; Carruthers, Jean; Lizzul, Paul F; Gross, Todd M; Beddingfield, Frederick C; Somogyi, Christine

2018-02-01

ATX-101 (deoxycholic acid injection) is the only injectable drug approved for submental fat (SMF) reduction. In the phase 3 REFINE trials, adults with moderate or severe SMF who were dissatisfied with the appearance of their face/chin were eligible to receive up to 6 treatment sessions with ATX-101 (2 mg/cm2) or placebo. Primary and secondary endpoints, evaluated at 12 weeks after last treatment, significantly favored ATX-101 supporting its efficacy for reducing SMF and the psychological impact of SMF, and increasing satisfaction with the appearance of the face/chin. To evaluate the efficacy and safety of ATX-101 by treatment session. This post-hoc analysis used pooled data from the REFINE trials to evaluate efficacy endpoints and adverse events following each treatment session to further characterize the ATX-101 treatment response and safety profile. In both treatment groups, mean injection volume declined over subsequent treatment sessions, though more markedly in the ATX-101 group. The majority of ATX-101-treated subjects achieved a ≥1-grade improvement in SMF within 2 to 4 treatment sessions based on either clinician or subject assessment. Furthermore, 19.1% of ATX-101-treated subjects (vs 3.9% of placebo-treated subjects) received fewer than 6 treatment sessions owing to subject satisfaction with treatment or lack of sufficient SMF for further treatment. In both treatment groups, the incidence/severity of common injection-site adverse events declined over subsequent treatment sessions. Although up to 6 treatment sessions were permitted in the REFINE trials, most ATX-101-treated subjects achieved an improvement in SMF within 2 to 4 treatment sessions. © 2018 The American Society for Aesthetic Plastic Surgery, Inc.

Efficacy of opioids versus placebo in chronic pain: a systematic review and meta-analysis of enriched enrollment randomized withdrawal trials.

PubMed

Meske, Diana S; Lawal, Oluwadolapo D; Elder, Harrison; Langberg, Valerie; Paillard, Florence; Katz, Nathaniel

2018-01-01

Opioids have been used for millennia for the treatment of pain. However, the long-term efficacy of opioids to treat chronic non-cancer pain continues to be debated. To evaluate opioids' efficacy in chronic non-cancer pain, we performed a meta-analysis of published clinical trials for μ-opioid receptor agonists performed for US Food and Drug Administration approval. MEDLINE and Cochrane trial register were searched for enriched enrollment randomized withdrawal studies (before June 2016). Selection criteria included: adults, ≥10 subjects per arm, any chronic pain condition, double-blind treatment period lasting ≥12 weeks, and all μ-agonist opioids approved in the USA. Fifteen studies met criteria. Opioid efficacy was statistically significant ( p <0.001) versus placebo for pain intensity (standardized mean difference: -0.416), ≥30% and ≥50% improvement in pain (risk difference: 0.166 and 0.137), patient global impression of change (0.163), and patient global assessment of study medication (0.194). There were minor benefits on physical function and no effect on mental function. Opioids are efficacious in the treatment of chronic non-cancer pain for up to 3 months in randomized controlled trials. This should be considered, alongside data on opioid safety, in the use of opioids for the treatment of chronic pain.

Explanatory Versus Pragmatic Trials: An Essential Concept in Study Design and Interpretation.

PubMed

Merali, Zamir; Wilson, Jefferson R

2017-11-01

Randomized clinical trials often represent the highest level of clinical evidence available to evaluate the efficacy of an intervention in clinical medicine. Although the process of randomization serves to maximize internal validity, the external validity, or generalizability, of such studies depends on several factors determined at the design phase of the trial including eligibility criteria, study setting, and outcomes of interest. In general, explanatory trials are optimized to demonstrate the efficacy of an intervention in a highly selected patient group; however, findings from these studies may not be generalizable to the larger clinical problem. In contrast, pragmatic trials attempt to understand the real-world benefit of an intervention by incorporating design elements that allow for greater generalizability and clinical applicability of study results. In this article we describe the explanatory-pragmatic continuum for clinical trials in greater detail. Further, a well-accepted tool for grading trials on this continuum is described, and applied, to 2 recently published trials pertaining to the surgical management of lumbar degenerative spondylolisthesis.

Nintedanib (OFEV) in the treatment of idiopathic pulmonary fibrosis.

PubMed

Fukihara, Jun; Kondoh, Yasuhiro

2016-12-01

Nintedanib is a new anti-fibrosis agent that is an intracellular tyrosine kinase inhibitor targeting platelet derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor. Although nintedanib is attracting much attention as a new treatment option for patients with idiopathic pulmonary fibrosis (IPF), the clinical evidence is limited mainly to the results from the dose-deciding phase II TOMORROW trial and phase III INPULSIS trials, which evaluated efficacy and safety of nintedanib for patients with IPF, prespecified subgroup analyses, pooled analyses and meta-analyses derived from those trials. Areas covered: In this document, we mainly reviewed reports on working mechanisms of nintedanib, and efficacy and safety of nintedanib for patients with IPF. The literature search was undertaken using Pub Med. Expert commentary: It is unknown whether the efficacy of nintedanib in patients enrolled in the clinical trials will be the same for the entire spectrum of patients, including patients unfit for the clinical trials due to age, severity, timing of IPF diagnosis or diagnosis of interstitial pneumonias other than IPF. Sufficient consideration should be given when selecting candidates for nintedanib in the real world.

Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting.

PubMed

Deck, Daniel H; Jordan, Jennifer M; Holland, Thomas L; Fan, Weihong; Wikler, Matthew A; Sulham, Katherine A; Ralph Corey, G

2016-09-01

Introduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting. SOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared. Overall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%). Single-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting. The Medicines Company, Parsippany, NJ, USA. ClinicalTrials.gov identifiers, NCT01252719 (SOLO I) and NCT01252732 (SOLO II).

Conditional estimation using prior information in 2-stage group sequential designs assuming asymptotic normality when the trial terminated early.

PubMed

Shimura, Masashi; Maruo, Kazushi; Gosho, Masahiko

2018-04-23

Two-stage designs are widely used to determine whether a clinical trial should be terminated early. In such trials, a maximum likelihood estimate is often adopted to describe the difference in efficacy between the experimental and reference treatments; however, this method is known to display conditional bias. To reduce such bias, a conditional mean-adjusted estimator (CMAE) has been proposed, although the remaining bias may be nonnegligible when a trial is stopped for efficacy at the interim analysis. We propose a new estimator for adjusting the conditional bias of the treatment effect by extending the idea of the CMAE. This estimator is calculated by weighting the maximum likelihood estimate obtained at the interim analysis and the effect size prespecified when calculating the sample size. We evaluate the performance of the proposed estimator through analytical and simulation studies in various settings in which a trial is stopped for efficacy or futility at the interim analysis. We find that the conditional bias of the proposed estimator is smaller than that of the CMAE when the information time at the interim analysis is small. In addition, the mean-squared error of the proposed estimator is also smaller than that of the CMAE. In conclusion, we recommend the use of the proposed estimator for trials that are terminated early for efficacy or futility. Copyright © 2018 John Wiley & Sons, Ltd.

Pharmacodynamic and pharmacokinetic evaluation of buprenorphine + samidorphan for the treatment of major depressive disorder.

PubMed

Ragguett, Renee-Marie; Rong, Carola; Rosenblat, Joshua D; Ho, Roger C; McIntyre, Roger S

2018-04-01

Treatment resistant depression (TRD) represents approximately 20% of all individuals receiving care for major depressive disorder. The opioidergic system is identified as a novel target which hitherto has not been sufficiently investigated in adults with TRD. The combination product buprenorphine + samidorphan is an opioid modulatory agent which has demonstrated replicated evidence of efficacy in TRD without abuse liability. Areas covered: Databases Pubmed, Google Scholar and clinicaltrials.gov were searched from inception through December 2017 for clinical trial information, pharmacokinetics, and pharmacodynamics of buprenorphine + samidorphan. Herein we provide a summary of the available information. Eight clinical trials were identified for inclusion, of the eight trials, five trials had available results and are included in detail in our review. Expert opinion: Buprenorphine + samidorphan has demonstrated efficacy in TRD. Extant evidence surrounding the safety and tolerability profile of buprenorphine + samidorphan does not identify any significant safety concerns. Additional studies are needed in order to assess the long-term safety and efficacy of this product.

Evaluating Study Withdrawal Among Biologics and Immunomodulators in Treating Ulcerative Colitis: A Meta-analysis of Controlled Clinical Trials.

PubMed

Shah, Eric D; Siegel, Corey A; Chong, Kelly; Melmed, Gil Y

2016-04-01

We conducted a systematic review and meta-analysis to evaluate the efficacy and adverse event (AE)-associated tolerability of treatment with immunomodulators and biologics in ulcerative colitis clinical trials. We performed a literature search of PubMed and the Cochrane databases to identify randomized placebo-controlled trials of immunomodulators and biologics. Tolerability was defined through study withdrawal due to AEs and efficacy through clinical response in induction trials and clinical remission in maintenance trials. We performed meta-analyses using a random-effects model to determine relative risks (RRs) of efficacy and study withdrawal. Number needed to treat (NNT) and number needed to stop (NNS) were determined. The ratio of NNS/NNT was calculated, with a higher ratio indicating a greater number of patients in remission for every AE study discontinuation. We examined 13 single-agent trials representing biologics (infliximab, adalimumab, golimumab, and vedolizumab) and immunomodulators (tacrolimus and azathioprine). Induction therapy did not result in excess study withdrawal with immunomodulators (RR = 0.9, 95% CI 0.1-12.0) or biologics (RR = 0.7, 95% CI 0.3-1.8), therefore the NNS/NNT ratio could not be assessed because of high tolerability. Maintenance immunomodulator therapy resulted in a NNS of 14 (RR = 2.8, 95% CI 0.7-10.5) and NNS/NNT ratio of 2.4 in 2 trials. Biologics did not result in excess study withdrawal in maintenance (RR = 0.7, 95% CI 0.3-1.7) or combined induction-and-maintenance (RR = 0.6, 95% CI 0.4-1.0) trials. Biologics were not associated with a higher RR of study withdrawal due to AE than placebo. There were insufficient data to compare these results with immunomodulators.

Challenges of assessing the clinical efficacy of asexual blood-stage Plasmodium falciparum malaria vaccines.

PubMed

Sheehy, Susanne H; Douglas, Alexander D; Draper, Simon J

2013-09-01

In the absence of any highly effective vaccine candidate against Plasmodium falciparum malaria, it remains imperative for the field to pursue all avenues that may lead to the successful development of such a formulation. The development of a subunit vaccine targeting the asexual blood-stage of Plasmodium falciparum malaria infection has proven particularly challenging with only limited success to date in clinical trials. However, only a fraction of potential blood-stage vaccine antigens have been evaluated as targets, and a number of new promising candidate antigen formulations and delivery platforms are approaching clinical development. It is therefore essential that reliable and sensitive methods of detecting, or ruling out, even modest efficacy of blood-stage vaccines in small clinical trials be established. In this article we evaluate the challenges facing blood-stage vaccine developers, assess the appropriateness and limitations of various in vivo approaches for efficacy assessment and suggest future directions for the field.

What can HIV vaccine trials teach us about future HIV vaccine dissemination?

PubMed Central

Newman, Peter A.; Duan, Naihua; Kakinami, Lisa; Roberts, Kathleen

2008-01-01

Summary This investigation explored commonalities and differences in barriers and motivators to HIV vaccine trial participation and acceptability of future U.S. Food and Drug Administration (FDA)-approved HIV vaccines in order to identify implications of clinical trials for future HIV vaccine dissemination. Fifteen focus groups were conducted with 157 predominately ethnic minority and low income participants recruited using venue-based sampling in Los Angeles. Data were analyzed using narrative thematic analysis. Barriers and motivators in common across willingness to participate (WTP) in HIV vaccine trials and future HIV vaccine acceptability (e.g., concerns about vaccine-induced infection, false-positives, side effects, efficacy, mistrust and stigma) suggest clinical trials present significant opportunities to develop and evaluate empirically based interventions to support future HIV vaccine dissemination. Barriers specific to HIV vaccine acceptability (e.g., concerns about duration of protection, cross-clade protection, cost and access) also indicate the need for formative research focused specifically on future dissemination. Protection motivation, common to WTP and acceptability, highlights the need to provide and evaluate prevention counseling and education in clinical trials, which may form the basis of evidence-informed preventive interventions to be launched in tandem with dissemination of partial efficacy HIV vaccines. PMID:18420313

Considerations in the Efficacy and Effectiveness of Virtual Reality Interventions for Stroke Rehabilitation: Moving the Field Forward

PubMed Central

Lange, Belinda

2015-01-01

In the past 2 decades, researchers have demonstrated the potential for virtual reality (VR) technologies to provide engaging and motivating environments for stroke rehabilitation interventions. Much of the research has been focused on the exploratory phase, and jumps to intervention efficacy trials and scale-up evaluation have been made with limited understanding of the active ingredients in a VR intervention for stroke. The rapid pace of technology development is an additional challenge for this emerging field, providing a moving target for researchers developing and evaluating potential VR technologies. Recent advances in customized games and cutting-edge technology used for VR are beginning to allow for researchers to understand and control aspects of the intervention related to motivation, engagement, and motor control and learning. This article argues for researchers to take a progressive, step-wise approach through the stages of intervention development using evidence-based principles, take advantage of the data that can be obtained, and utilize measurement tools to design effective VR interventions for stroke rehabilitation that can be assessed through carefully designed efficacy and effectiveness trials. This article is motivated by the recent calls in the field of rehabilitation clinical trials research for carefully structured clinical trials that have progressed through the phases of research. PMID:25343960

Considerations in the efficacy and effectiveness of virtual reality interventions for stroke rehabilitation: moving the field forward.

PubMed

Proffitt, Rachel; Lange, Belinda

2015-03-01

In the past 2 decades, researchers have demonstrated the potential for virtual reality (VR) technologies to provide engaging and motivating environments for stroke rehabilitation interventions. Much of the research has been focused on the exploratory phase, and jumps to intervention efficacy trials and scale-up evaluation have been made with limited understanding of the active ingredients in a VR intervention for stroke. The rapid pace of technology development is an additional challenge for this emerging field, providing a moving target for researchers developing and evaluating potential VR technologies. Recent advances in customized games and cutting-edge technology used for VR are beginning to allow for researchers to understand and control aspects of the intervention related to motivation, engagement, and motor control and learning. This article argues for researchers to take a progressive, step-wise approach through the stages of intervention development using evidence-based principles, take advantage of the data that can be obtained, and utilize measurement tools to design effective VR interventions for stroke rehabilitation that can be assessed through carefully designed efficacy and effectiveness trials. This article is motivated by the recent calls in the field of rehabilitation clinical trials research for carefully structured clinical trials that have progressed through the phases of research. © 2015 American Physical Therapy Association.

Efficacy and safety of maropitant, a selective neurokinin 1 receptor antagonist, in two randomized clinical trials for prevention of vomiting due to motion sickness in dogs.

PubMed

Conder, G A; Sedlacek, H S; Boucher, J F; Clemence, R G

2008-12-01

Maropitant (Cerenia), a selective neurokinin(1) receptor antagonist, was evaluated for efficacy and safety in prevention of vomiting due to motion sickness in dogs in two randomized clinical trials. One-hundred eighty-nine dogs with a history of motion sickness were enrolled at 26 veterinary clinics (across 12 US states) across the two trials; of these, 163 were fully evaluable, 19 were evaluable only for safety, and seven were not evaluable. Each trial used a two-period crossover design. Each dog was treated orally with placebo or maropitant (minimum dose of 8 mg/kg body weight using unit dosing) tablets at approximately 2 h (Trial 1) or 10 h (Trial 2) before an automobile ride of approximately 60 min, during which dogs were observed for signs of motion sickness. Following a 10-14-day washout period, each dog was administered the opposite treatment and taken for another journey (same route, driver and vehicle). Maropitant reduced the occurrence of vomiting compared to placebo by 86.1% or 76.5% when given approximately 2 or 10 h prior to travel, respectively. No significant clinical signs were observed after maropitant treatment. Maropitant was safe and effective in preventing vomiting due to motion sickness in dogs when administered at a minimum dose of 8 mg/kg body weight as oral tablets 2 or 10 h prior to travel.

Hyperhidrosis plantaris - a randomized, half-side trial for efficacy and safety of an antiperspirant containing different concentrations of aluminium chloride.

PubMed

Streker, Meike; Reuther, Tilmann; Hagen, Linda; Kerscher, Martina

2012-02-01

Primary focal hyperhidrosis plantaris can cause impairment in social, physical, leisure and occupational activities. Topical treatment with aluminium chloride is the first-line treatment. The aim of this trial was to evaluate efficacy and safety of two different concentrations of aluminium chloride hexa-hydrate (12.5%, 30%) for 6 weeks. 20 volunteers with hyperhidrosis plantaris were included. Efficacy was evaluated using a clinical rating scale of the hyperhidrosis level and qualitative assessments including Minor's (iodine-starch) test and a standardized sniff test. Furthermore a patient questionnaire and measurements of skin surface pH were done to evaluate the subjective assessments and side effects. The hyperhidrosis level significantly decreased in both concentrations. There were no differences in tolerability regarding the skin surface pH and the patient questionnaires. In addition the hidrotic areas decreased after application of both products and the sniff test improved. Topical application of an antiperspirant containing aluminium chloride reduced sweat production in plantar hyperhidrosis significantly. As both 12.5% and 30% were efficacious and safe, we would recommend 12.5% for outpatient treatment. © The Author • Journal compilation © Blackwell Verlag GmbH, Berlin.

Postdose 3 G1 serum neutralizing antibody as correlate of protection for pentavalent rotavirus vaccine.

PubMed

Liu, G Frank; Hille, Darcy; Kaplan, Susan S; Goveia, Michelle G

2017-10-03

Although clinical trials of the pentavalent rotavirus vaccine (RotaTeq®, RV5) have demonstrated efficacy against RV gastroenteritis (RGE) in low and high-income settings, a clear correlate of protection or a measure of immune response that could predict efficacy has yet to be identified. This is the first time that immunogenicity data with both serum neutralized antibody (SNA) titers and anti-RV IgA titers from several clinical efficacy trials were pooled to provide a unique context for evaluating the correlation between immunogenicity and RGE risk or efficacy of RV5. The correlation between immunogenicity and RGE risk is evaluated with data at the individual subject level. The analyses show that higher Postdose 3 (PD3) G1 SNA titers are associated with lower odds of contracting any RGE. The correlation between immunogenicity and efficacy is assessed using aggregated population level data, which shows higher efficacy associated with higher PD3 G1 SNA geometric mean titer (GMT) ratio (between RV5 and placebo) and PD3 serum anti-RV IgA GMT ratio. Among high-income countries, efficacy plateaus over the range of PD3 G1 SNA GMT ratios and PD3 serum anti-RV IgA GMT ratios. From both individual- and population-level analyses, PD3 G1 SNA titers correlated most closely with the RGE risk or efficacy for RV5.

Efficacy Outcome Measures for Procedural Sedation Clinical Trials in Adults: An ACTTION Systematic Review.

PubMed

Williams, Mark R; McKeown, Andrew; Dexter, Franklin; Miner, James R; Sessler, Daniel I; Vargo, John; Turk, Dennis C; Dworkin, Robert H

2016-01-01

Successful procedural sedation represents a spectrum of patient- and clinician-related goals. The absence of a gold-standard measure of the efficacy of procedural sedation has led to a variety of outcomes being used in clinical trials, with the consequent lack of consistency among measures, making comparisons among trials and meta-analyses challenging. We evaluated which existing measures have undergone psychometric analysis in a procedural sedation setting and whether the validity of any of these measures support their use across the range of procedures for which sedation is indicated. Numerous measures were found to have been used in clinical research on procedural sedation across a wide range of procedures. However, reliability and validity have been evaluated for only a limited number of sedation scales, observer-rated pain/discomfort scales, and satisfaction measures in only a few categories of procedures. Typically, studies only examined 1 or 2 aspects of scale validity. The results are likely unique to the specific clinical settings they were tested in. Certain scales, for example, those requiring motor stimulation, are unsuitable to evaluate sedation for procedures where movement is prohibited (e.g., magnetic resonance imaging scans). Further work is required to evaluate existing measures for procedures for which they were not developed. Depending on the outcomes of these efforts, it might ultimately be necessary to consider measures of sedation efficacy to be procedure specific.

Sexual risk behaviour of Canadian participants in the first efficacy trial of a preventive HIV-1 vaccine

PubMed Central

Lampinen, Thomas M.; Chan, Keith; Remis, Robert S.; Fikre Merid, Maraki; Rusch, Melanie; Vincelette, Jean; Logue, Ken; Popovic, Vladimir; Alary, Michel; Schechter, Martin T.; Hogg, Robert S.

2005-01-01

Background Phase I and phase II HIV-1 vaccine trials have revealed increases in risky sexual activity among study subjects during the trials, perhaps because the subjects believe that the vaccine being tested is efficacious; subjects may thus suffer harm from their participation. We evaluated the sexual behaviour of Canadian men who have sex with men (MSM) who participated in the phase III Vax004 trial of an HIV-1 vaccine. Methods Using self-reports of sexual behaviours during the 6 months before trial entry as a baseline, we determined changes in reported sexual behaviour after 6, 12 and 18 months of participation in the trial. Results Of 291 HIV-seronegative MSM enrolled from July to October 1999, 260 (89%) completed 18 months of follow-up, 19 (7%) experienced seroconversion, and 12 (4%) did not complete follow-up. Unprotected receptive anal intercourse during the previous 6 months with partners whose HIV-1 serostatus was positive or unknown was reported by 21% of men at enrolment and by 27% at any point during 18 months of follow-up. No increase in this behaviour from baseline was reported by participants, including among men who were motivated to enrol because of expected protection from HIV-1 infection, men who believed they had received the vaccine, men who believed that the vaccine had greater than 50% efficacy, or men who believed that they had received the vaccine and that vaccine efficacy was greater than 50%. Interpretation MSM can be successfully enrolled in HIV-1 vaccine efficacy trials without evident increases in those sexual behaviours most associated with HIV-1 risk. PMID:15710939

A randomized, double-blind, controlled clinical trial to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy volunteers.

PubMed

Jang, Hee-Chang; Kim, Choong Jong; Kim, Kye Hyoung; Lee, Kwang-Hee; Byun, Young-Ho; Seong, Baik-Lin; Saletti, Giulietta; Czerkinsky, Cecil; Park, Wan Beom; Park, Sang-Won; Kim, Hong-Bin; Kim, Nam Joong; Oh, Myoung-don

2010-08-16

A randomized, double-blind, controlled clinical trial was conducted to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, and to determine its minimum effective dose. The overall rates of cutaneous "take" reaction and humoral and cellular immunogenicity in CJ-50300 vaccinees were 100% (123/123), 99.2% (122/123), and 90.8% (109/120), respectively, and these rates did not differ significantly between the conventional-dose and the low-dose CJ-50300 (1.0x10(8) and 1.0x10(7) plaque-forming units/mL, respectively) (P>0.05 for each). No serious adverse reaction was observed. However, one case of possible generalized vaccinia occurred in the conventionally dosed group [ClinicalTrials.gov Identifier: NCT00607243].

Role of preliminary registry data in development of a clinical trial for an innovative device: a small but integral piece of a health policy initiative

PubMed Central

Ricci, Donald R.; de Vries, Joost; Blanc, Raphael

2017-01-01

ABSTRACT Establishing a national health policy at a macro level involves the integration of a series of health initiatives across a spectrum of activities, including clinical care. Evaluation of the safety and efficacy of a new medical device ultimately evolves to testing in humans. The pathway to a formal prospective clinical trial includes a stepwise appreciation of pre-clinical data and detailed analysis of data obtained from preliminary registries, where information about appropriate patient selection and use of the device is obtained. Evaluation of procedural and follow-up efficacy and safety data in a preliminary series of cases, chosen to simulate published data, allows the design and conduct of clinical trials that are required to verify preliminary observations, closing the loop on one aspect of modifying health policy decisions. PMID:28321285

Generalizing boundaries for triangular designs, and efficacy estimation at extended follow-ups.

PubMed

Allison, Annabel; Edwards, Tansy; Omollo, Raymond; Alves, Fabiana; Magirr, Dominic; E Alexander, Neal D

2015-11-16

Visceral leishmaniasis (VL) is a parasitic disease transmitted by sandflies and is fatal if left untreated. Phase II trials of new treatment regimens for VL are primarily carried out to evaluate safety and efficacy, while pharmacokinetic data are also important to inform future combination treatment regimens. The efficacy of VL treatments is evaluated at two time points, initial cure, when treatment is completed and definitive cure, commonly 6 months post end of treatment, to allow for slow response to treatment and detection of relapses. This paper investigates a generalization of the triangular design to impose a minimum sample size for pharmacokinetic or other analyses, and methods to estimate efficacy at extended follow-up accounting for the sequential design and changes in cure status during extended follow-up. We provided R functions that generalize the triangular design to impose a minimum sample size before allowing stopping for efficacy. For estimation of efficacy at a second, extended, follow-up time, the performance of a shrinkage estimator (SHE), a probability tree estimator (PTE) and the maximum likelihood estimator (MLE) for estimation was assessed by simulation. The SHE and PTE are viable approaches to estimate an extended follow-up although the SHE performed better than the PTE: the bias and root mean square error were lower and coverage probabilities higher. Generalization of the triangular design is simple to implement for adaptations to meet requirements for pharmacokinetic analyses. Using the simple MLE approach to estimate efficacy at extended follow-up will lead to biased results, generally over-estimating treatment success. The SHE is recommended in trials of two or more treatments. The PTE is an acceptable alternative for one-arm trials or where use of the SHE is not possible due to computational complexity. NCT01067443 , February 2010.

Analgesic efficacy of preoperative dexketoprofen trometamol: A systematic review and meta-analysis.

PubMed

Esparza-Villalpando, Vicente; Pozos-Guillén, Amaury; Masuoka-Ito, David; Gaitán-Fonseca, César; Chavarría-Bolaños, Daniel

2018-03-01

Post-Market Research Clinical evidence supports the use of dexketoprofen trometamol (DEX) to manage acute postoperative pain. However, controversies surround the impact of the use of this drug in preoperative analgesic protocols. The aim of the present meta-analysis was to evaluate the effectiveness of the preoperative administration of DEX under postoperative pain conditions. Electronic and manual searches were conducted through diverse electronic databases. A systematic review and meta-analysis to evaluate the analgesic efficacy of the preoperative administration of DEX was performed including Randomized Clinical Trials (RCTs) published between 2002 and 2017. Suitable individual studies were evaluated through a quality system, and the data were extracted and analyzed. Fourteen RTCs were included (12 parallel trials and 2 cross-over trials), published in the English and Turkish languages. Follow-up periods ranged from 4, 6, 8, 24, and 48 hr. All trials measured the outcome result as Acute Pain Level (APL) (VAS, NRS, VRS), time to requiring a second dose of DEX or analgesic emergency and consumption of opioids via patient-controlled analgesia. When the comparators were other drugs - paracetamol, Lornoxicam or placebo during the preoperative time, preoperative administration of DEX was superior. When the comparison comprised preoperative and postoperative DEX, both alternatives exhibited comparable analgesic effects. The analgesic efficacy of the preoperative administration of DEX when compared to placebo, lornoxicam, and paracetamol on postoperative pain was evident. Preoperative administration of DEX compared to its immediate postoperative administration showed a similar analgesic effect. © 2017 Wiley Periodicals, Inc.

Why European and United States drug regulators are not speaking with one voice on anti-influenza drugs: regulatory review methodologies and the importance of 'deep' product reviews.

PubMed

Mulinari, Shai; Davis, Courtney

2017-11-09

Relenza represents the first neuraminidase inhibitor (NI), a class of drugs that also includes the drug Tamiflu. Although heralded as breakthrough treatments in influenza, NI efficacy has remained highly controversial. A key unsettled question is why the United States Food and Drug Administration (FDA) has approved more cautious efficacy statements in labelling than European regulators for both drugs. We conducted a qualitative analysis of United States and European Union regulatory appraisals for Relenza to investigate the reasons for divergent regulatory interpretations, pertaining to Relenza's capacity to alleviate symptoms and reduce frequency of complications of influenza. In Europe, Relenza was evaluated via the so-called national procedure with Sweden as the reference country. We show that FDA reviewers, unlike their European (i.e. Swedish) counterpart, (1) rejected the manufacturer's insistence on pooling efficacy data, (2) remained wary of subgroup analyses, and (3) insisted on stringent statistical analyses. These differences meant that the FDA was less likely to depart from prevailing regulatory and scientific standards in interpreting trial results. We argue that the differences are explained largely by divergent institutionalised review methodologies, i.e. the European regulator's reliance on manufacturer-compiled summaries compared to the FDA's examination of original data and documentation from trials. The FDA's more probing and meticulous evaluative methodology allowed its reviewers to develop 'deep' knowledge concerning the clinical and statistical facets of trials, and more informed opinions regarding suitable methods for analysing trial results. These findings challenge the current emphasis on evaluating regulatory performance mainly in terms of speed of review. We propose that persistent uncertainty and knowledge deficits regarding NIs could have been ameliorated had regulators engaged in the public debates over the drugs' efficacy and explained their contrasting methodologies and judgments. Regulators use major resources to evaluate drugs, but if regulators' assessments are not effectively disseminated and used, resources are used inefficiently.

Huangqi injection (a traditional Chinese patent medicine) for chronic heart failure: a systematic review.

PubMed

Fu, Shufei; Zhang, Junhua; Menniti-Ippolito, Francesca; Gao, Xiumei; Galeotti, Francesca; Massari, Marco; Hu, Limin; Zhang, Boli; Ferrelli, Rita; Fauci, Alice; Firenzuoli, Fabio; Shang, Hongcai; Guerra, Ranieri; Raschetti, Roberto

2011-05-06

Chronic heart failure (CHF) is a global public health problem. Therefore, novel and effective drugs that show few side-effects are needed. Early literature studies indicated that Huangqi injection is one of the most commonly used traditional Chinese patent medicines for CHF in China. As a large number of clinical studies has been carried out and published, it is essential to evaluate the effectiveness and safety of Huangqi injection. Therefore, we carried out this systematic review under the support of the framework of the Joint Sino-Italian Laboratory (JoSIL). To evaluate the efficacy and safety of Huangqi injection for CHF according to the available scientific knowledge. An extensive search including PubMed, EMBASE, CBM, the Cochrane Library and Chinese literature databases was performed up to July 2008. Clinical trials regarding Huangqi injection for the treatment of CHF were searched for, irrespective of languages. The quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0, and RevMan 5.0 provided by the Cochrane Collaboration and STATA 9.2 were used for data analysis. After selection of 1,205 articles, 62 RCTs and quasi-RCTs conducted in China and published in Chinese journals were included in the review. The methodological quality of the trials was low. In most trials inclusion and exclusion criteria were not specified. Furthermore, only one study evaluated the outcomes for drug efficacy after an adequate period of time. For these reasons and because of the different baseline characteristics we did not conduct a meta-analysis. Although available studies are not adequate to draw a conclusion on the efficacy and safety of Huangqi injection (a traditional Chinese patent medicine), we hope that our work could provide useful experience on further studies on Huangqi injections. The overall level of TCM clinical research needs to be improved so that the efficacy of TCM can be evaluated by the international community and possibly some TCM can enter into the international market.

Type 1 Diabetes TrialNet--an international collaborative clinical trials network.

PubMed

Skyler, Jay S; Greenbaum, Carla J; Lachin, John M; Leschek, Ellen; Rafkin-Mervis, Lisa; Savage, Peter; Spain, Lisa

2008-12-01

Type 1 Diabetes TrialNet is an international consortium of clinical research centers aimed at the prevention or delay of type 1 diabetes (T1D). The fundamental goal of TrialNet is to counter the T1D disease process by immune modulation and/or enhancement of beta cell proliferation and regeneration. To achieve this goal, TrialNet researchers are working to better understand the natural history of the disease, to identify persons at risk, and to clinically evaluate novel therapies that balance potential risks and benefits. The particular focus is on studies of preventive measures. In addition, TrialNet evaluates therapies in individuals with newly diagnosed T1D with preserved beta cell function to help determine the risk/benefit profile and gain an initial assessment of potential efficacy in preservation of beta cell function, so that promising agents can be studied in prevention trials. In addition, TrialNet evaluates methodologies that enhance the conduct of its clinical trials, which includes tests of outcome assessment methodology, the evaluation of surrogate markers, and mechanistic studies laying the foundation for future clinical trials.

Evaluation of the Frails' Fall Efficacy by Comparing Treatments (EFFECT) on reducing fall and fear of fall in moderately frail older adults: study protocol for a randomised control trial

PubMed Central

2011-01-01

Background Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo® Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo® Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline. Methods This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments. Discussions The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000576022 PMID:21682909

Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report.

PubMed

Ramsey, Scott D; Willke, Richard J; Glick, Henry; Reed, Shelby D; Augustovski, Federico; Jonsson, Bengt; Briggs, Andrew; Sullivan, Sean D

2015-03-01

Clinical trials evaluating medicines, medical devices, and procedures now commonly assess the economic value of these interventions. The growing number of prospective clinical/economic trials reflects both widespread interest in economic information for new technologies and the regulatory and reimbursement requirements of many countries that now consider evidence of economic value along with clinical efficacy. As decision makers increasingly demand evidence of economic value for health care interventions, conducting high-quality economic analyses alongside clinical studies is desirable because they broaden the scope of information available on a particular intervention, and can efficiently provide timely information with high internal and, when designed and analyzed properly, reasonable external validity. In 2005, ISPOR published the Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials: The ISPOR RCT-CEA Task Force report. ISPOR initiated an update of the report in 2014 to include the methodological developments over the last 9 years. This report provides updated recommendations reflecting advances in several areas related to trial design, selecting data elements, database design and management, analysis, and reporting of results. Task force members note that trials should be designed to evaluate effectiveness (rather than efficacy) when possible, should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects. Collection of economic data should be fully integrated into the study. An incremental analysis should be conducted with an intention-to-treat approach, complemented by relevant subgroup analyses. Uncertainty should be characterized. Articles should adhere to established standards for reporting results of cost-effectiveness analyses. Economic studies alongside trials are complementary to other evaluations (e.g., modeling studies) as information for decision makers who consider evidence of economic value along with clinical efficacy when making resource allocation decisions. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Comparison of the efficacy of dispensing granules with traditional decoction: a systematic review and meta-analysis

PubMed Central

Qiu, Ruijin; Zhang, Xiaoyu; Zhao, Chen; Li, Min

2018-01-01

Background Dispensing granules have been developed for about 20 years. However, whether they are as effective as the traditional decoction kept unclear. This systematic review and meta-analysis was made to assess the efficacy of dispensing granules compared with traditional decoction. Methods We searched four databases since their inception to 9th September in 2016. Two authors independently identified trials, extracted data and assessed risk of bias with Cochrane Reviewer’s Handbook 5.0. We conducted meta-analysis with RevMan 5.1.0 software for eligible and appropriate trials. Results In the end, 7,035 participants from 51 randomized controlled trials (RCTs) which compared dispensing granules with traditional decoction were included in this systematic review. There were 33 different kinds of diseases for investigation, of which 8 RCTs observed common cold, 4 RCTs observed migraine. For rheumatoid arthritis, insomnia and hypertension, there were 3 RCTs reported respectively. The last RCTs reported different kinds of diseases in one or two trials. The majority of trials were in low methodological quality. Thirty-eight (74.5%) RCTs showed that the efficacy of dispensing granules were similar with traditional decoction, 6 (11.8%) RCTs reported that the therapeutic efficacy of dispensing granules were significantly better than traditional decoction. We conducted meta-analysis for 4 trials investigating patients with migraine. The results showed that dispensing granules reduced headache frequency by about 1.03 attacks per month as compared to traditional decoction. No evidence was found in terms of migraine intensity and duration. Conclusions The low quality of RCTs and conflicting results made it difficult to draw a definite conclusion. In the future, it needs much more evidence to explore the efficacy and safety of dispensing granules. N-of-1 trials and fuzzy comprehensive evaluation methods may be better choices for assessing the efficacy of them than RCTs. PMID:29610730

Brief Treatments for Cannabis Dependence: Findings From a Randomized Multisite Trial

ERIC Educational Resources Information Center

Babor, Thomas F.

2004-01-01

This study evaluated the efficacy of 2 brief interventions for cannabis-dependent adults. A multisite randomized controlled trial compared cannabis use outcomes across 3 study conditions: (a) 2 sessions of motivational enhancement therapy (MET); (b) 9 sessions of multicomponent therapy that included MET, cognitive-behavioral therapy, and case…

The E Sibling Project – exploratory randomised controlled trial of an online multi-component psychoeducational intervention for siblings of individuals with first episode psychosis

PubMed Central

2013-01-01

Background Siblings of individuals with first episode psychosis are natural partners to promote service users’ recovery and are themselves vulnerable to mental ill health due to the negative impact of psychosis within the family. This study aims to develop and undertake a preliminary evaluation of the efficacy of an online multi-component psychoeducational intervention for siblings of individuals with first episode psychosis. The impetus for the intervention arose from siblings' expressed needs for peer support and information on psychosis, coping and management strategies for common symptoms and ways to promote recovery. Methods/Design The project design draws on the Medical Research Council framework for the design and evaluation of complex interventions. Mixed methods comprising collection of qualitative focus group data, systematic review and expert advisory group consultation are used to develop the theoretical basis for and design of the intervention. This protocol focuses on the modelling and piloting phase which uses a randomised controlled trial with factorial design to test the efficacy of the intervention. Outcome data on participants’ mental wellbeing, knowledge, perceived self-efficacy and experiences of caregiving will be assessed at baseline, at end of the intervention (10 weeks later) and at 10 week follow-up. In addition, a post-intervention semi-structured interview with 20% of the participants will explore their experiences and acceptability of the intervention. Discussion This multi-component online psychoeducational intervention aims to enhance siblings' knowledge about psychosis and their coping capacity, thus potentially improving their own mental wellbeing and promoting their contribution to service users’ recovery. The factorial design randomised controlled trial with a supplementary process evaluation using semi-structured interviews and usage-monitoring will collect preliminary evidence of efficacy, feasibility and acceptability, as well as feedback about the barriers and strategies to using such an innovative resource. The RCT will provide data for estimating the likely effect size of the intervention on outcomes for siblings and inform the development of a definitive future trial. Trial registration Trial registration: ISRCTN01416694 PMID:23622123

Rationale for the tinnitus retraining therapy trial.

PubMed

Formby, Craig; Scherer, Roberta

2013-01-01

The Tinnitus Retraining Therapy Trial (TRTT) is a National Institutes of Health-sponsored, multi-centered, placebo-controlled, randomized trial evaluating the efficacy of tinnitus retraining therapy (TRT) and its component parts, directive counseling and sound therapy, as treatments for subjective debilitating tinnitus in the military. The TRTT will enroll 228 individuals at an allocation ratio of 1:1:1 to: (1) directive counseling and sound therapy using conventional sound generators; (2) directive counseling and placebo sound generators; or (3) standard of care as administered in the military. Study centers include a Study Chair's Office, a Data Coordinating Center, and six Military Clinical Centers with treatment and data collection standardized across all clinics. The primary outcome is change in Tinnitus Questionnaire (TQ) score assessed longitudinally at 3, 6, 12, and 18-month follow-up visits. Secondary outcomes include: Change in TQ sub-scales, Tinnitus Handicap Inventory, Tinnitus Functional Index, and TRT interview visual analog scale; audiometric and psychoacoustic measures; and change in quality of life. The TRTT will evaluate TRT efficacy by comparing TRT (directive counseling and conventional sound generators) with standard of care; directive counseling by comparing directive counseling plus placebo sound generators versus standard of care; and sound therapy by comparing conventional versus placebo sound generators. We hypothesize that full TRT will be more efficacious than standard of care, directive counseling and placebo sound generators more efficacious than standard of care, and conventional more efficacious than placebo sound generators in habituating the tinnitus awareness, annoyance, and impact on the study participant's life.

Points to consider: efficacy and safety evaluations in the clinical development of ultra-orphan drugs.

PubMed

Maeda, Kojiro; Kaneko, Masayuki; Narukawa, Mamoru; Arato, Teruyo

2017-08-23

The unmet medical needs of individuals with very rare diseases are high. The clinical trial designs and evaluation methods used for 'regular' drugs are not applicable in the clinical development of ultra-orphan drugs (<1000 patients) in many cases. In order to improve the clinical development of ultra-orphan drugs, we examined several points regarding the efficient evaluations of drug efficacy and safety that could be conducted even with very small sample sizes, based on the review reports of orphan drugs approved in Japan. The clinical data packages of 43 ultra-orphan drugs approved in Japan from January 2001 to December 2014 were investigated. Japanese clinical trial data were not included in the clinical data package for eight ultra-orphan drugs, and non-Japanese clinical trial data were included for six of these eight drug. Japanese supportive data that included retrospective studies, published literature, clinical research and Japanese survey results were clinical data package attachments in 22 of the 43 ultra-orphan drugs. Multinational trials were conducted for three ultra-orphan drugs. More than two randomized controlled trials (RCTs) were conducted for only 11 of the 43 ultra-orphan drugs. The smaller the number of patients, the greater the proportion of forced titration and optional titration trials were conducted. Extension trials were carried out for enzyme preparations and monoclonal antibodies with high ratio. Post-marketing surveillance of all patients was required in 36 of the 43 ultra-orphan drugs. For ultra-orphan drugs, clinical endpoints were used as the primary efficacy endpoint of the pivotal trial only for two drugs. The control groups in RCTs were classified as follows: placebo groups different dosage groups, and active controls groups. Sample sizes have been determined on the basis of feasibility for some ultra-orphan drugs. We provide "Draft Guidance on the Clinical Development of Ultra-Orphan Drugs" based on this research. The development of ultra-orphan drugs requires various arrangements regarding evidence collection, data sources and the clinical trial design. We expect that this draft guidance is useful for ultra-orphan drugs developments in future.

Methodological Flaws, Conflicts of Interest, and Scientific Fallacies: Implications for the Evaluation of Antidepressants' Efficacy and Harm.

PubMed

Hengartner, Michael P

2017-01-01

In current psychiatric practice, antidepressants are widely and with ever-increasing frequency prescribed to patients. However, several scientific biases obfuscate estimates of antidepressants' efficacy and harm, and these are barely recognized in treatment guidelines. The aim of this mini-review is to critically evaluate the efficacy and harm of antidepressants for acute and maintenance treatment with respect to systematic biases related to industry funding and trial methodology. Narrative review based on a comprehensive search of the literature. It is shown that the pooled efficacy of antidepressants is weak and below the threshold of a minimally clinically important change once publication and reporting biases are considered. Moreover, the small mean difference in symptom reductions relative to placebo is possibly attributable to observer effects in unblinded assessors and patient expectancies. With respect to trial dropout rates, a hard outcome not subjected to observer bias, no difference was observed between antidepressants and placebo. The discontinuation trials on the efficacy of antidepressants in maintenance therapy are systematically flawed, because in these studies, spontaneous remitters are excluded, whereas half of all patients who remitted on antidepressants are abruptly switched to placebo. This can cause a severe withdrawal syndrome that is easily misdiagnosed as a relapse when assessed on subjective symptom rating scales. In accordance, the findings of naturalistic long-term studies suggest that maintenance therapy has no clear benefit, and non-drug users do not show increased recurrence rates. Moreover, a growing body of evidence from hundreds of randomized controlled trials suggests that antidepressants cause suicidality, but this risk is underestimated because data from industry-funded trials are systematically flawed. Unselected, population-wide observational studies indicate that depressive patients who use antidepressants are at an increased risk of suicide and that they have a higher rate of all-cause mortality than matched controls. The strong reliance on industry-funded research results in an uncritical approval of antidepressants. Due to several flaws such as publication and reporting bias, unblinding of outcome assessors, concealment and recoding of serious adverse events, the efficacy of antidepressants is systematically overestimated, and harm is systematically underestimated. Therefore, I conclude that antidepressants are largely ineffective and potentially harmful.

[Design requirements for clinical trials on re-evaluation of safety and efficacy of post-marketed Chinese herbs].

PubMed

Xie, Yanming; Wei, Xu

2011-10-01

Re-evaluation of post-marketed based on pharmacoepidemiology is to study and collect clinical medicine safety in large population under practical applications for a long time. It is necessary to conduct re-evaluation of clinical effectiveness because of particularity of traditional Chinese medicine (TCM). Right before carrying out clinical trials on re-evaluation of post-marketed TCM, we should determine the objective of the study and progress it in the assessment mode of combination of disease and syndrome. Specical population, involving children and seniors who were excluded in pre-marketed clinical trial, were brought into drug monitoring. Sample size needs to comply with statistical requirement. We commonly use cohort study, case-control study, nested case-control, pragmatic randomized controlled trials.

Evaluation of buspirone for relapse-prevention in adults with cocaine dependence: An efficacy trial conducted in the real world

PubMed Central

Winhusen, Theresa; Brady, Kathleen T.; Stitzer, Maxine; Woody, George; Lindblad, Robert; Kropp, Frankie; Brigham, Gregory; Liu, David; Sparenborg, Steven; Sharma, Gaurav; VanVeldhuisen, Paul; Adinoff, Bryon; Somoza, Eugene

2012-01-01

Cocaine dependence is a significant public health problem for which there are currently no FDA-approved medications. Hence, identifying candidate compounds and employing an efficient evaluation process is crucial. This paper describes key design decisions made for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) study that uses a novel two-stage process to evaluate buspirone (60 mg/day) for cocaine-relapse prevention. The study includes pilot (N=60) and full-scale (estimated N=264) trials. Both trials will be randomized, double-blind, and placebo-controlled and both will enroll treatment-seeking cocaine-dependent participants engaged in inpatient/residential treatment and scheduled for outpatient treatment post-discharge. All participants will receive contingency management in which incentives are given for medication adherence as evaluated by the Medication Events Monitoring System (MEMS). The primary outcome measure is maximum days of continuous cocaine abstinence, as assessed by twice-weekly urine drug screens (UDS) and self-report, during the 15-week outpatient treatment phase. Drug-abuse outcomes include cocaine use as assessed by UDS and self-report of cocaine use, other substance use as assessed by UDS and self-report of substance use (i.e., alcohol and/or illicit drugs), cocaine bingeing, HIV risk behavior, quality of life, functioning, and substance-abuse treatment attendance. Unique aspects of the study include conducting an efficacy trial in community treatment programs, a two-stage process to efficiently evaluate buspirone, and an evaluation of mediators by which buspirone might exert a beneficial effect on relapse prevention. PMID:22613054

Evaluation of buspirone for relapse-prevention in adults with cocaine dependence: an efficacy trial conducted in the real world.

PubMed

Winhusen, Theresa; Brady, Kathleen T; Stitzer, Maxine; Woody, George; Lindblad, Robert; Kropp, Frankie; Brigham, Gregory; Liu, David; Sparenborg, Steven; Sharma, Gaurav; Vanveldhuisen, Paul; Adinoff, Bryon; Somoza, Eugene

2012-09-01

Cocaine dependence is a significant public health problem for which there are currently no FDA-approved medications. Hence, identifying candidate compounds and employing an efficient evaluation process is crucial. This paper describes key design decisions made for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) study that uses a novel two-stage process to evaluate buspirone (60 mg/day) for cocaine-relapse prevention. The study includes pilot (N=60) and full-scale (estimated N=264) trials. Both trials will be randomized, double-blind, and placebo-controlled and both will enroll treatment-seeking cocaine-dependent participants engaged in inpatient/residential treatment and scheduled for outpatient treatment post-discharge. All participants will receive contingency management in which incentives are given for medication adherence as evaluated by the Medication Events Monitoring System (MEMS). The primary outcome measure is maximum days of continuous cocaine abstinence, as assessed by twice-weekly urine drug screens (UDS) and self-report, during the 15-week outpatient treatment phase. Drug-abuse outcomes include cocaine use as assessed by UDS and self-report of cocaine use, other substance use as assessed by UDS and self-report of substance use (i.e., alcohol and/or illicit drugs), cocaine bingeing, HIV risk behavior, quality of life, functioning, and substance abuse treatment attendance. Unique aspects of the study include conducting an efficacy trial in community treatment programs, a two-stage process to efficiently evaluate buspirone, and an evaluation of mediators by which buspirone might exert a beneficial effect on relapse prevention. Copyright © 2012 Elsevier Inc. All rights reserved.

The use of a battery of tracking tests in the quantitative evaluation of neurological function

NASA Technical Reports Server (NTRS)

Repa, B. S.; Albers, J. W.; Potvin, A. R.; Tourtellotte, W. W.

1972-01-01

A tracking test battery has been applied in a drug trail designed to compare the efficacy of L-DOPA and amantadine to that of L-DOPA and placebo in the treatment of 28 patients with Parkinson's disease. The drug trial provided an ideal opportunity for objectively evaluating the usefulness of tracking tests in assessing changes in neurologic function. Evaluating changes in patient performance resulting from disease progression and controlled clinical trials is of great importance in establishing effective treatment programs.

A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

PubMed

Zang, Yong; Lee, J Jack

2017-01-15

We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The efficacy of a movement control exercise programme to reduce injuries in youth rugby: a cluster randomised controlled trial

PubMed Central

Hislop, M D; Stokes, K A; Williams, S; McKay, C D; England, M; Kemp, S P T

2016-01-01

Background Injuries to youth rugby players have become an increasingly prominent health concern, highlighting the importance of developing and implementing appropriate preventive strategies. A growing body of evidence from other youth sports has demonstrated the efficacy of targeted exercise regimens to reduce injury risk. However, studies have yet to investigate the effect of such interventions in youth contact sport populations like rugby union. Objective To determine the efficacy of an evidence-based movement control exercise programme compared with a sham exercise programme to reduce injury risk in youth rugby players. Exercise programme compliance between trial arms and the effect of coach attitudes on compliance will also be evaluated. Setting School rugby coaches in England will be the target of the researcher intervention, with the effects of the injury prevention programmes being measured in male youth players aged 14–18 years in school rugby programmes over the 2015–2016 school winter term. Methods A cluster-randomised controlled trial with schools randomly allocated to either a movement control exercise programme or a sham exercise programme, both of which are coach-delivered. Injury measures will derive from field-based injury surveillance, with match and training exposure and compliance recorded. A questionnaire will be used to evaluate coach attitudes, knowledge, beliefs and behaviours both prior to and on the conclusion of the study period. Outcome measures Summary injury measures (incidence, severity and burden) will be compared between trial arms, as will the influence of coach attitudes on compliance and injury burden. Additionally, changes in these outcomes through using the exercise programmes will be evaluated. Trial registration number ISRTCNN13422001. PMID:27900148

A Randomized Controlled Trial of the Child Anxiety Multi-Day Program (CAMP) for Separation Anxiety Disorder

ERIC Educational Resources Information Center

Santucci, Lauren C.; Ehrenreich-May, Jill

2013-01-01

While the efficacy of cognitive behavior therapy for childhood anxiety disorders, including separation anxiety disorder (SAD), has been established, tailoring such treatments to particular interests and needs may enhance uptake of evidence-based interventions. The current investigation evaluates the feasibility and preliminary efficacy of an…

Promoting Assessment Efficacy through an Integrated System for Online Clinical Assessment of Practical Skills

ERIC Educational Resources Information Center

Hay, Peter J.; Engstrom, Craig; Green, Anita; Friis, Peter; Dickens, Sue; Macdonald, Doune

2013-01-01

This paper presents evaluation outcomes from an externally funded research project involving the online clinical assessment of practical skills (eCAPS) using web-based video technologies within a university medical programme. eCAPS was implemented to trial this web-based approach for promoting the efficacy of "practical" skills…

Rationale, Design, and Methods of the Preschool ADHD Treatment Study (PATS)

ERIC Educational Resources Information Center

Kollins, Scott; Greenhill, Laurence; Swanson, James; Wigal, Sharon; Abikoff, Howard; McCracken, James; Riddle, Mark; McGough, James; Vitiello, Benedetto; Wigal, Tim; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Davies, Mark; Cunningham, Charles; Bauzo, Audrey

2006-01-01

Objective: To describe the rationale and design of the Preschool ADHD Treatment Study (PATS). Method: PATS was a National Institutes of Mental Health-funded, multicenter, randomized, efficacy trial designed to evaluate the short-term (5 weeks) efficacy and long-term (40 weeks) safety of methylphenidate (MPH) in preschoolers with…

The Efficacy of Behavioral Interventions in Reducing HIV Risk Behaviors and Incident Sexually Transmitted Diseases in Heterosexual African Americans

PubMed Central

Darbes, Lynae; Crepaz, Nicole; Lyles, Cynthia; Kennedy, Gail; Rutherford, George

2009-01-01

Objective To conduct a meta-analytic review of HIV interventions for heterosexual African Americans to determine the overall efficacy in reducing HIV-risk sex behaviors and incident sexually transmitted diseases (STD) and identify intervention characteristics associated with efficacy. Methods Comprehensive searches included electronic databases from 1988 to 2005, handsearches of journals, reference lists of articles, and contacts with researchers. Thirty-eight randomized controlled trials met the selection criteria. Random-effects models were used to aggregate data. Results Interventions significantly reduced unprotected sex (OR = 0.75, 95% CI = 0.67, 0.84, 35 trials, N = 14,682) and marginally significantly decreased incident STD (OR = 0.88, 95% CI = 0.72, 1.07, 10 trials, n = 10,944). Intervention characteristics associated with efficacy include: (1) culturally tailored, (2) aiming to influence social norms in promoting safe sex behaviour, (3) utilizing peer education, (4) providing skills training on correct use of condoms and communication skills needed for negotiating safer sex, and (5) multiple sessions and opportunities to practice learned skills. Conclusion Interventions targeting heterosexual African Americans are efficacious in reducing HIV-risk sex behaviors. Efficacious intervention components identified in this review should be incorporated into the development of future interventions and further evaluated for effectiveness. PMID:18525264

Traditional medicine in the treatment of drug addiction.

PubMed

Lu, Lin; Liu, Yanli; Zhu, Weili; Shi, Jie; Liu, Yu; Ling, Walter; Kosten, Thomas R

2009-01-01

To evaluate clinical trials and neurochemical mechanisms of the action of traditional herbal remedies and acupuncture for treating drug addiction. We used computerized literature searches in English and Chinese and examined texts written before these computerized databases existed. We used search terms of treatment and neurobiology of herbal medicines, and acupuncture for drug abuse and dependence. Acupuncture showed evidence for clinical efficacy and relevant neurobiological mechanisms in opiate withdrawal, but it showed poor efficacy for alcohol and nicotine withdrawal or relapse prevention, and no large studies supported its efficacy for cocaine in well-designed clinical trials. Clinical trials were rare for herbal remedies. Radix Puerariae showed the most promising efficacy for alcoholism by acting through daidzin, which inhibits mitocochondrial aldehyde dehydrogenase 2 and leads to disulfiram-like alcohol reactions. Peyote also has some evidence for alcoholism treatment among Native Americans. Ginseng and Kava lack efficacy data in addictions, and Kava can be hepatotoxic. Thunbergia laurifolia can protect against alcoholic liver toxicity. Withania somnifera and Salvia miltiorrhiza have no efficacy data, but can reduce morphine tolerance and alcohol intake, respectively, in animal models. Traditional herbal treatments can compliment pharmacotherapies for drug withdrawal and possibly relapse prevention with less expense and perhaps fewer side effects with notable exceptions. Both acupuncture and herbal treatments need testing as adjuncts to reduce doses and durations of standard pharmacotherapies.

Bio-efficacy, physical integrity, community usage and washing practices of mosquito nets treated with ICON MAXX long-lasting insecticidal treatment in India

PubMed Central

Sahu, Sudhansu Sekhar; Gunasekaran, Kasinathan; Vijayakumar, Kilakootil Narayanan; Jambulingam, Purushothaman

2017-01-01

BACKGROUND New brands of potential long lasting insecticide nets (LLINs) and LLIN treatment kits require field evaluation before they are used in a vector control programme. OBJECTIVES The aim of this study was to evaluate the bio-efficacy, usage, washing practice and physical integrity of nets treated with LLIN treatment kit, ICON MAXX in a phase III field trial in Odisha state, India. METHODS A total of 300 polyester nets treated with ICON MAXX and 140 polyester nets treated conventionally with lambda-cyhalothrin CS 2.5% ITNs were distributed. The bio-efficacy was evaluated with WHO cone bioassay. The chemical analysis of netting pieces was done at the beginning, after 12 and 36 months of the trial. FINDINGS After one year of distribution of nets, the bioassay showed 100% mortality on both ITNs and ICON MAXX treated nets. At 36 months, the overall pass rate was 58.8% and the mean lambda-cyhalothrin content of LLINs was 34.5 mg ai/m2, showing a loss of 44.4% of the original concentration. CONCLUSION ICON MAXX treated LLIN was found to retain bio-efficacy causing 97% knockdown of Anopheles stephensi up to 30 months and met the WHOPES criteria. However, the desired bio-efficacy was not sustained up to 36 months. PMID:28125134

The efficacy of systemic therapy for childhood and adolescent externalizing disorders: a systematic review of 47 RCT.

PubMed

von Sydow, Kirsten; Retzlaff, Ruediger; Beher, Stefan; Haun, Markus W; Schweitzer, Jochen

2013-12-01

Systemic (family) therapy is a widely used psychotherapy approach. However, most systematic efficacy reviews have focused solely on "family-based treatment" rather than on the theoretic orientation "systemic therapy." We systematically review trials on the efficacy of systemic therapy for the treatment of childhood and adolescent externalizing disorders. All randomized (or matched) controlled trials (RCT) evaluating systemic/systems-oriented therapy in various forms (family, individual, group, multi-family group therapy) with child or adolescent index patients (0-17 years) suffering from mental disorders were identified by data base searches and cross-references. Inclusion criteria were as follows: index patient diagnosed with a DSM- or ICD-listed mental disorder, and trial published in any language up to the end of 2011. The RCTs were analyzed for their research methodology, interventions applied, and results (postintervention; follow-up). A total of 47 trials from the United States, Europe, and China, published in English, German, and Mandarin, were identified. A total of 42 of them showed systemic therapy to be efficacious for the treatment of attention deficit hyperactivity disorders, conduct disorders, and substance use disorders. Results were stable across follow-up periods of up to 14 years. There is a sound evidence base for the efficacy of systemic therapy for children and adolescents (and their families) diagnosed with externalizing disorders. © FPI, Inc.

Using Data Augmentation to Facilitate Conduct of Phase I–II Clinical Trials with Delayed Outcomes

PubMed Central

Jin, Ick Hoon; Liu, Suyu; Thall, Peter F.; Yuan, Ying

2014-01-01

A practical impediment in adaptive clinical trials is that outcomes must be observed soon enough to apply decision rules to choose treatments for new patients. For example, if outcomes take up to six weeks to evaluate and the accrual rate is one patient per week, on average three new patients will be accrued while waiting to evaluate the outcomes of the previous three patients. The question is how to treat the new patients. This logistical problem persists throughout the trial. Various ad hoc practical solutions are used, none entirely satisfactory. We focus on this problem in phase I–II clinical trials that use binary toxicity and efficacy, defined in terms of event times, to choose doses adaptively for successive cohorts. We propose a general approach to this problem that treats late-onset outcomes as missing data, uses data augmentation to impute missing outcomes from posterior predictive distributions computed from partial follow-up times and complete outcome data, and applies the design’s decision rules using the completed data. We illustrate the method with two cancer trials conducted using a phase I–II design based on efficacy-toxicity trade-offs, including a computer stimulation study. PMID:25382884

Neurorehabilitation in Parkinson's Disease: A Critical Review of Cognitive Rehabilitation Effects on Cognition and Brain.

PubMed

Díez-Cirarda, María; Ibarretxe-Bilbao, Naroa; Peña, Javier; Ojeda, Natalia

2018-01-01

Parkinson's disease (PD) patients experience cognitive impairment which has been related to reduced quality of life and functional disability. These symptoms usually progress until dementia occurs. Some studies have been published assessing the efficacy of cognitive treatments on improving cognition, functional outcome, and producing changes in brain activity. A critical review was performed to present up-to-date neurorehabilitation effects of cognitive rehabilitation in PD, with special emphasis on the efficacy on cognition, quality of life aspects, brain changes, and the longitudinal maintenance of these changes. After exclusions, 13 studies were reviewed, including 6 randomized controlled trials for the efficacy on cognition, 2 randomized controlled trials regarding the brain changes after cognitive training, and 5 studies which evaluated the long-term effects of cognitive treatments. Cognitive rehabilitation programs have demonstrated to be effective on improving cognitive functions, but more research is needed focusing on the efficacy on improving behavioral aspects and producing brain changes in patients with PD. Moreover, there is a need of randomized controlled trials with long-term follow-up periods.

Randomized Controlled Trial of a Preventive Intervention for Perinatal Depression in High-Risk Latinas

ERIC Educational Resources Information Center

Le, Huynh-Nhu; Perry, Deborah F.; Stuart, Elizabeth A.

2011-01-01

Objective: A randomized controlled trial was conducted to evaluate the efficacy of a cognitive-behavioral (CBT) intervention to prevent perinatal depression in high-risk Latinas. Method: A sample of 217 participants, predominantly low-income Central American immigrants who met demographic and depression risk criteria, were randomized into usual…

Evaluation of Parent and Child Enhancement (PACE) Program: Randomized Controlled Trial

ERIC Educational Resources Information Center

Leung, Cynthia; Tsang, Sandra; Lo, Cyrus

2017-01-01

Objective: This study examined the efficacy of the Parent and Child Enhancement (PACE) program on child learning, child behavior problems, and parental stress, using randomized controlled trial design, in social services centers. Methods: Eligibility criteria were (1) children aged 2 years at program commencement, (2) low-income, new immigrant, or…

A Compound Herbal Preparation (CHP) in the Treatment of Children with ADHD: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Katz, M.; Adar Levine, A.; Kol-Degani, H.; Kav-Venaki, L.

2010-01-01

Objective: Evaluation of the efficacy of a patented, compound herbal preparation (CHP) in improving attention, cognition, and impulse control in children with ADHD. Method: Design: A randomized, double-blind, placebo-controlled trial. Setting: University-affiliated tertiary medical center. Participants: 120 children newly diagnosed with ADHD,…

76 FR 23324 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31, rm... Cardiovascular Risk in Diabetes-Lipid (ACCORD Lipid) trial as they relate to the efficacy and safety of the... cholesterol goal. The ACCORD Lipid study was a randomized, double-blind, placebo- controlled add-on trial...

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

PubMed Central

Goldman, Mitchel P.

2017-01-01

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

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

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

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

Espresso Coffee for the Treatment of Somnolence in Parkinson’s Disease: Results of n-of-1 Trials

PubMed Central

Ferreira, Joaquim J.; Mestre, Tiago; Guedes, Leonor Correia; Coelho, Miguel; Rosa, Mário M.; Santos, Ana T.; Barra, Márcio; Sampaio, Cristina; Rascol, Olivier

2016-01-01

There is limited information available concerning the treatment of daytime somnolence associated with Parkinson’s disease (PD); the most frequently applied therapeutic strategies include decreasing the dose of dopamine agonists or adding potential wake-promoting agents. There is recent data from a placebo-controlled trial concluding on a non-significant trend in favor of caffeine. We aimed to evaluate the efficacy of espresso-coffee in the treatment of daytime somnolence in PD. To evaluate the efficacy of espresso-coffee in the treatment of daytime somnolence in PD, we have conducted multiple single-patient (n-of-1) clinical trials comparing regular espresso coffee to decaffeinated coffee in PD patients presenting moderate to severe daytime somnolence defined as an Epworth Sleepiness Scale score >9. Each single-patient (n-of-1) trial included a sequence of three crossovers (two treatment periods separated by two days of washout). Four patients were included in the studies and three completed the three pairs of treatment periods. In two of the four patients, espresso coffee was considered beneficial. This study concludes that multiple single patient trials are feasible in PD and suggests that espresso-coffee may have a beneficial effect on daytime somnolence in some patients. These results cannot be generalized beyond the patients included in these trials. PMID:27014181

Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.).

PubMed

Tamayo, Carmen; Diamond, Suzanne

2007-06-01

Milk thistle extracts have been used as traditional herbal remedies for almost 2000 years. The extracts are still widely used to protect the liver against toxins and to control chronic liver diseases. Recent experimental and clinical studies suggest that milk thistle extracts also have anticancer, antidiabetic, and cardioprotective effects. This article reviews clinical trials of milk thistle conducted in the past 5 years including pharmacokinetic and toxicity studies, herb-drug interactions, and other safety issues. Several trials have studied the effects of milk thistle for patients with liver diseases, cancer, hepatitis C, HIV, diabetes, and hypercholesterolemia. Promising results have been reported in the protective effect of milk thistle in certain types of cancer, and ongoing trials will provide more evidence about this effect. In addition, new established doses and improvement on the quality and standardization of this herb will provide the much-awaited evidence about the efficacy of milk thistle in the treatment of liver diseases. Milk thistle extracts are known to be safe and well tolerated, and toxic or adverse effects observed in the reviewed clinical trials seem to be minimal. The future of milk thistle research is promising, and high-quality randomized clinical trials on milk thistle versus placebo may be needed to further demonstrate the safety and efficacy of this herb.

Guidelines for the Reporting of Treatment Trials for Alcohol Use Disorders

PubMed Central

Witkiewitz, Katie; Finney, John W.; Harris, Alex H.S; Kivlahan, Daniel R.; Kranzler, Henry R.

2015-01-01

Background The primary goals in conducting clinical trials of treatments for alcohol use disorders (AUDs) is to identify efficacious treatments and determine which treatments are most efficacious for which patients. Accurate reporting of study design features and results is imperative to enable readers of research reports to evaluate to what extent a study has achieved these goals. Guidance on quality of clinical trial reporting has evolved substantially over the past two decades, primarily through the publication and widespread adoption of the Consolidated Standards of Reporting Trials (CONSORT) statement. However, there is room to improve the adoption of those standards in reporting the design and findings of treatment trials for AUD. Methods Narrative review of guidance on reporting quality in AUD treatment trials. Results Despite improvements in the reporting of results of treatment trials for AUD over the past two decades, many published reports provide insufficient information on design or methods. Conclusions The reporting of alcohol treatment trial design, analysis, and results requires improvement in four primary areas: (1) trial registration, (2) procedures for recruitment and retention, (3) procedures for randomization and intervention design considerations, and (4) statistical methods used to assess treatment efficacy. Improvements in these areas and the adoption of reporting standards by authors, reviewers, and editors are critical to an accurate assessment of the reliability and validity of treatment effects. Continued developments in this area are needed to move AUD treatment research forward via systematic reviews and meta-analyses that maximize the utility of completed studies. PMID:26259958

Comparative efficacy of simultaneous versus sequential multiple health behavior change interventions among adults: A systematic review of randomised trials.

PubMed

James, Erica; Freund, Megan; Booth, Angela; Duncan, Mitch J; Johnson, Natalie; Short, Camille E; Wolfenden, Luke; Stacey, Fiona G; Kay-Lambkin, Frances; Vandelanotte, Corneel

2016-08-01

Growing evidence points to the benefits of addressing multiple health behaviors rather than single behaviors. This review evaluates the relative effectiveness of simultaneous and sequentially delivered multiple health behavior change (MHBC) interventions. Secondary aims were to identify: a) the most effective spacing of sequentially delivered components; b) differences in efficacy of MHBC interventions for adoption/cessation behaviors and lifestyle/addictive behaviors, and; c) differences in trial retention between simultaneously and sequentially delivered interventions. MHBC intervention trials published up to October 2015 were identified through a systematic search. Eligible trials were randomised controlled trials that directly compared simultaneous and sequential delivery of a MHBC intervention. A narrative synthesis was undertaken. Six trials met the inclusion criteria and across these trials the behaviors targeted were smoking, diet, physical activity, and alcohol consumption. Three trials reported a difference in intervention effect between a sequential and simultaneous approach in at least one behavioral outcome. Of these, two trials favoured a sequential approach on smoking. One trial favoured a simultaneous approach on fat intake. There was no difference in retention between sequential and simultaneous approaches. There is limited evidence regarding the relative effectiveness of sequential and simultaneous approaches. Given only three of the six trials observed a difference in intervention effectiveness for one health behavior outcome, and the relatively consistent finding that the sequential and simultaneous approaches were more effective than a usual/minimal care control condition, it appears that both approaches should be considered equally efficacious. PROSPERO registration number: CRD42015027876. Copyright © 2016 Elsevier Inc. All rights reserved.

French version of the Copenhagen neck functional disability scale.

PubMed

Forestier, Romain; Françon, Alain; Arroman, Frédérique Saint; Bertolino, Christiane

2007-03-01

We conducted a study to validate the French version of the Copenhagen Neck Functional Disability Scale (CNFDS). We used the CNFDS on data generated by a previous randomized controlled trial comparing pulsed electromagnetic field therapy (PEMFT), spa therapy, and standard therapy in patients with neck pain. Patients were recruited locally and examined by a physician who was unaware of the treatment group and independent from the trial. Treatment efficacy was evaluated based on a visual analog scale (VAS) for pain, the short-form-36 quality-of-life instrument (SF36), payments by public healthcare insurance, and overall assessments by the patients and physicians. Efficacy was evaluated at baseline, at treatment completion, and after 3 and 6 months. In addition, the patients completed the CNFDS at these time points. CNFDS scores were normally distributed. CNFDS scores and their variations correlated well with the other efficacy criteria. CNFDS scores were less sensitive to change than the VAS pain scores and more sensitive to change than the other efficacy criteria. The CNFDS holds promise as a tool for evaluating neck pain. Score reproducibility needs to be studied. The CNFDS can be added to the other instruments that have been translated in recent years to serve as tools for clinical research. However, the ease of completion of the CNFDS is consistent with use in clinical practice.

Feasibility and Efficacy of the Nintendo Wii Gaming System to Improve Balance Performance Post-Stroke: Protocol of a Phase II Randomized Controlled Trial in an Inpatient Rehabilitation Setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2013-04-01

Balance deficits following stroke are common and debilitating. Commercially available gaming systems, such as the Nintendo(®) (Kyoto, Japan) Wii™, have been widely adopted clinically; however, there is limited evidence supporting their feasibility and efficacy for improving balance performance following stroke. The aim of this trial is to investigate the clinical feasibility and efficacy of using the Nintendo Wii gaming system as an adjunct to standard care to improve balance performance following stroke in an inpatient rehabilitation setting. Thirty participants undergoing inpatient stroke rehabilitation will be recruited into this Phase II, single-blind, randomized controlled trial. Participants will be allocated into a Balance or Upper Limb Group, and both groups will perform activities using the Nintendo Wii in addition to their standard care. Participants will attend three 45-minute sessions per week, for a minimum of 2 and a maximum of 4 weeks. The main focus of the study is to investigate the feasibility of the intervention protocol. This will be evaluated through recruitment, retention, adherence, acceptability, and safety. The Step Test and Functional Reach Test will be the primary efficacy outcomes. Secondary outcomes will include force platform, mobility, and upper limb measures. Assessments will occur at baseline, 2 weeks, and 4 weeks after study entry. To the authors' knowledge, this will be the largest randomized clinical trial to investigate the feasibility and efficacy of the Nintendo Wii gaming system for improving balance performance in a stroke population. The results will inform the design of a Phase III multicenter trial.

Efficacy of phase 3 trial of RTS, S/AS01 malaria vaccine: The need for an alternative development plan.

PubMed

Mahmoudi, Shima; Keshavarz, Hossein

2017-09-02

Although vaccines would be the ideal tool for control, prevention, elimination, and eradication of many infectious diseases, developing of parasites vaccines such as malaria vaccine is very complex. The most advanced malaria vaccine candidate RTS,S, a pre-erythrocytic vaccine, has been recommended for licensure by EMEA. The results of this phase III trial suggest that this candidate malaria vaccine has relatively little efficacy, and the vaccine apparently will not meet the goal of malaria eradication by itself. Since there are many vaccine candidates in the pipeline 1 that are being evaluated in vaccine trials, further study on using of alternative parasite targets and vaccination strategies are highly recommended.

Rationale and design of the Clinical Evaluation of Magnetic Resonance Imaging in Coronary heart disease 2 trial (CE-MARC 2): A prospective, multicenter, randomized trial of diagnostic strategies in suspected coronary heart disease

PubMed Central

Ripley, David P.; Brown, Julia M.; Everett, Colin C.; Bijsterveld, Petra; Walker, Simon; Sculpher, Mark; McCann, Gerry P.; Berry, Colin; Plein, Sven; Greenwood, John P.

2015-01-01

Background A number of investigative strategies exist for the diagnosis of coronary heart disease (CHD). Despite the widespread availability of noninvasive imaging, invasive angiography is commonly used early in the diagnostic pathway. Consequently, approximately 60% of angiograms reveal no evidence of obstructive coronary disease. Reducing unnecessary angiography has potential financial savings and avoids exposing the patient to unnecessary risk. There are no large-scale comparative effectiveness trials of the different diagnostic strategies recommended in international guidelines and none that have evaluated the safety and efficacy of cardiovascular magnetic resonance. Trial Design CE-MARC 2 is a prospective, multicenter, 3-arm parallel group, randomized controlled trial of patients with suspected CHD (pretest likelihood 10%-90%) requiring further investigation. A total of 1,200 patients will be randomized on a 2:2:1 basis to receive 3.0-T cardiovascular magnetic resonance–guided care, single-photon emission computed tomography–guided care (according to American College of Cardiology/American Heart Association appropriate-use criteria), or National Institute for Health and Care Excellence guidelines–based management. The primary (efficacy) end point is the occurrence of unnecessary angiography as defined by a normal (>0.8) invasive fractional flow reserve. Safety of each strategy will be assessed by 3-year major adverse cardiovascular event rates. Cost-effectiveness and health-related quality-of-life measures will be performed. Conclusions The CE-MARC 2 trial will provide comparative efficacy and safety evidence for 3 different strategies of investigating patients with suspected CHD, with the intension of reducing unnecessary invasive angiography rates. Evaluation of these management strategies has the potential to improve patient care, health-related quality of life, and the cost-effectiveness of CHD investigation. PMID:25497243

Clinical efficacy of a novel elimination diet composed of a mixture of amino acids and potatoes in dogs with non-seasonal pruritic dermatitis.

PubMed

Kawarai, Shinpei; Ishihara, Jun; Masuda, Kenichi; Yasuda, Nobutaka; Ohmori, Keitaro; Sakaguchi, Masahiro; Asami, Yasuhiro; Tsujimoto, Hajime

2010-11-01

There has been a need for improvement of the elimination diet used for diagnosis of adverse food reaction (AFR) in dogs. Recently, a novel elimination diet composed of a mixture of amino acids and potatoes was developed. We evaluated the efficacy of the elimination diet for diagnosis of AFR in dogs. Twenty dogs that were suspected to have allergic dermatitis were enrolled in a 2-month food elimination trial using the diet. Before and after the trial, the clinical symptoms were evaluated based on the change in canine atopic dermatitis extent and severity index (CADESI), pruritus score and medication score. Of the 20 dogs, 15 completed the food elimination trial. The remaining 5 dogs were removed from the trial because of diet unpalatability, skin disease progression or diarrhea. On the basis of evaluation of the clinical scores, we observed that the clinical symptoms improved in 11 of the 15 dogs that completed the food elimination trial. Provocative challenge was performed in 10 of the 11 dogs that showed improvement in their clinical symptoms. Of the 10 dogs, 7 were diagnosed as having AFR against food ingredients such as pork, beef, chicken and wheat because their skin symptoms reappeared after intake of these ingredients. The results of the food elimination trial and the provocative challenge indicated the usefulness of the novel elimination diet for diagnosis of AFR.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS.

PubMed

Gupta, Satish Kumar; Nutan

2013-10-22

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other sexually transmitted infections, and contraception will help in moving the field of microbicide development forward.

Clinical use of vaginal or rectally applied microbicides in patients suffering from HIV/AIDS

PubMed Central

Gupta, Satish Kumar; Nutan

2013-01-01

Microbicides, primarily used as topical pre-exposure prophylaxis, have been proposed to prevent sexual transmission of HIV. This review covers the trends and challenges in the development of safe and effective microbicides to prevent sexual transmission of HIV Initial phases of microbicide development used such surfactants as nonoxynol-9 (N-9), C13G, and sodium lauryl sulfate, aiming to inactivate the virus. Clinical trials of microbicides based on N-9 and C31G failed to inhibit sexual transmission of HIV. On the contrary, N-9 enhanced susceptibility to sexual transmission of HIV-1. Subsequently, microbicides based on polyanions and a variety of other compounds that inhibit the binding, fusion, or entry of virus to the host cells were evaluated for their efficacy in different clinical setups. Most of these trials failed to show either safety or efficacy for prevention of HIV transmission. The next phase of microbicide development involved antiretroviral drugs. Microbicide in the form of 1% tenofovir vaginal gel when tested in a Phase IIb trial (CAPRISA 004) in a coitally dependent manner revealed that tenofovir gel users were 39% less likely to become HIV-infected compared to placebo control. However, in another trial (VOICE MTN 003), tenofovir gel used once daily in a coitally independent mode failed to show any efficacy to prevent HIV infection. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS 001) employing a coitally dependent dosing regimen. Further, long-acting microbicide-delivery systems (vaginal ring) for slow release of such antiretroviral drugs as dapivirine are also undergoing clinical trials. Discovering new markers as correlates of protective efficacy, novel long-acting delivery systems with improved adherence in the use of microbicides, discovering new compounds effective against a broad spectrum of HIV strains, developing multipurpose technologies incorporating additional features of efficacy against other sexually transmitted infections, and contraception will help in moving the field of microbicide development forward. PMID:24174883

Evaluating the Efficacy of the PEAK Relational Training System Using a Randomized Controlled Trial of Children with Autism

ERIC Educational Resources Information Center

McKeel, Autumn Nicole; Dixon, Mark R.; Daar, Jacob H.; Rowsey, Kyle E.; Szekely, Susan

2015-01-01

The present investigation sought to examine the efficacy of the instructional curriculum described in the Direct Training Module of the PEAK Relational Training System on the language repertoires, as measured by the PEAK direct assessment, of children diagnosed with autism or related developmental disabilities. Twenty-seven children diagnosed with…

Efficacy of an Acceptance-Based Behavior Therapy for Generalized Anxiety Disorder: Evaluation in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Roemer, Lizabeth; Orsillo, Susan M.; Salters-Pedneault, Kristalyn

2008-01-01

Generalized anxiety disorder (GAD) is a chronic anxiety disorder, associated with comorbidity and impairment in quality of life, for which improved psychosocial treatments are needed. GAD is also associated with reactivity to and avoidance of internal experiences. The current study examined the efficacy of an acceptance-based behavioral therapy…

The potential impact of prophylactic human papillomavirus vaccination on oropharyngeal cancer.

PubMed

Guo, Theresa; Eisele, David W; Fakhry, Carole

2016-08-01

The incidence of oropharyngeal cancer (OPC) is significantly increasing in the United States. Given that these epidemiologic trends are driven by human papillomavirus (HPV), the potential impact of prophylactic HPV vaccines on the prevention of OPC is of interest. The primary evidence supporting the approval of current prophylactic HPV vaccines is from large phase 3 clinical trials focused on the prevention of genital disease (cervical and anal cancer, as well as genital warts). These trials reported vaccine efficacy rates of 89% to 98% for the prevention of both premalignant lesions and persistent genital infections. However, these trials were designed before the etiologic relationship between HPV and OPC was established. There are differences in the epidemiology of oral and genital HPV infection, such as differences in age and sex distributions, which suggest that the vaccine efficacy observed in genital cancers may not be directly translatable to the cancers of the oropharynx. Evaluation of vaccine efficacy is challenging in the oropharynx because no premalignant lesion analogous to cervical intraepithelial neoplasia in cervical cancer has yet been identified. To truly investigate the efficacy of these vaccines in the oropharynx, additional clinical trials with feasible endpoints are needed. Cancer 2016;122:2313-2323. © 2016 American Cancer Society. © 2016 American Cancer Society.

Vaccines for preventing typhoid fever.

PubMed

Anwar, Elspeth; Goldberg, Elad; Fraser, Abigail; Acosta, Camilo J; Paul, Mical; Leibovici, Leonard

2014-01-02

Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new, modified, conjugated Vi vaccine called Vi-rEPA, are in development. To evaluate the efficacy and adverse effects of vaccines used to prevent typhoid fever. In June 2013, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2013 and scanned the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease). Two review authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella typhi in blood. We calculated risk ratios (RRs) and efficacy (1-RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs were included in this review; 12 evaluated efficacy (Ty21a: five trials; Vi polysaccharide: six trials; Vi-rEPA: one trial), and 11 reported on adverse events. Ty21a vaccine (oral vaccine, three doses) A three-dose schedule of Ty21a vaccine prevents around one-third to one-half of typhoid cases in the first two years after vaccination (Year 1: 35%, 95% CI 8% to 54%; Year 2: 58%, 95% CI 40% to 71%; one trial, 20,543 participants; moderate quality evidence; data taken from a single trial conducted in Indonesia in the 1980s). No benefit was detected in the third year after vaccination. Four additional cluster-RCTs have been conducted, but the study authors did not adjust for clustering.Compared with placebo, this vaccine was not associated with more participants with vomiting, diarrhoea, nausea or abdominal pain (four trials, 2066 participants; moderate quality evidence) headache, or rash (two trials, 1190 participants; moderate quality evidence); however, fever (four trials, 2066 participants; moderate quality evidence) was more common in the vaccine group. Vi polysaccharide vaccine (injection, one dose) A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (Year 1: 69%, 95% CI 63% to 74%; three trials, 99,979 participants; high quality evidence). In Year 2, the trial results were more variable, with the vaccine preventing between 45% and 69% of typhoid cases (Year 2: 59%, 95% CI 45% to 69%; four trials, 194,969 participants; moderate quality evidence). The three-year cumulative efficacy of the vaccine is around 55% (95% CI 30% to 70%; 11,384 participants, one trial; moderate quality evidence). These data are taken from a single trial in South Africa in the 1980s.Compared with placebo, this vaccine was not associated with more participants with fever (four trials, 133,038 participants; moderate quality evidence) or erythema (three trials, 132,261 participants; low quality evidence); however, swelling (three trials, 1767 participants; moderate quality evidence) and pain at the injection site (one trial, 667 participants; moderate quality evidence) were more common in the vaccine group. Vi-rEPA vaccine (two doses) Administration of two doses of the Vi-rEPA vaccine prevents between 50% and 96% of typhoid cases during the first two years after vaccination (Year 1: 94%, 95% CI 75% to 99%; Year 2: 87%, 95% CI 56% to 96%; one trial, 12,008 participants; moderate quality evidence). These data are taken from a single trial with children 2 to 5 years of age conducted in Vietnam.Compared with placebo, the first and second doses of this vaccine were not associated with increased risk of adverse events. The first dose of this vaccine was not associated with fever (2 studies, 12,209 participants; low quality evidence), erythema (two trials, 12,209 participants; moderate quality evidence) or swelling at the injection site (two trials, 12,209 participants; moderate quality evidence). The second dose of this vaccine was not associated with fever (two trials, 11,286 participants; low quality evidence), erythema (two trials, 11,286 participants; moderate quality evidence) and swelling at the injection site (two trials, 11,286 participants; moderate quality evidence). The licensed Ty21a and Vi polysaccharide vaccines are efficacious. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity.

Design and evaluation of an aerial spray trial with true replicates to test the efficacy of Bacillus thuringiensis insecticide in a boreal forest.

PubMed

Cadogan, Beresford L; Scharbach, Roger D

2003-04-01

A field trial using true replicates was conducted successfully in a boreal forest in 1996 to evaluate the efficacy of two aerially applied Bacillus thuringiensis formulations, ABG 6429 and ABG 6430. A complete randomized design with four replicates per treatment was chosen. Twelve to 15 balsam fir (Abies balsamea [L.] Mill.) per plot were randomly selected as sample trees. Interplot buffer zones, > or = 200 m wide, adequately prevented cross contamination from sprays that were atomized with four rotary atomizers (volume median diameters ranging from 64.6 to 139.4 microm) and released approximately 30 m above the ground. The B. thuringiensis formulations were not significantly different (P > 0.05) from each other in reducing spruce budworm (Choristoneura fumiferana [Clem.]) populations and protecting balsam trees from defoliation but both formulations were significantly more efficacious than the controls. The results suggest that true replicates are a feasible alternative to pseudoreplication in experimental forest aerial applications.

Characteristics and publication patterns of obstetric studies registered in ClinicalTrials.gov.

PubMed

Stockmann, Chris; Sherwin, Catherine M T; Koren, Gideon; Campbell, Sarah C; Constance, Jonathan E; Linakis, Matthew; Balch, Alfred; Varner, Michael W; Spigarelli, Michael G

2014-04-01

Physiologic changes during pregnancy alter the pharmacokinetics, safety, and efficacy of many drugs. For clinicians, there is often uncertainty regarding the safety of these drugs due to a scarcity of published data. This study aimed to comprehensively evaluate the characteristics and publication patterns of obstetric studies registered in ClinicalTrials.gov from 2007 to 2012. Primary outcome measures, funding sources, inclusion criteria, and the reporting of study results were evaluated. A manual review of Medline/PubMed was performed to identify publications associated with studies registered in ClinicalTrials.gov. Of 93,709 total studies, there were 5,203 (6%) obstetric studies registered in ClinicalTrials.gov. Interventional studies accounted for 70% and 30% were observational. Clinical trials of drugs (49%), procedures (13%), and behavioral interventions (12%) were most common. Among interventional drug trials, 84% featured randomized allocation to study arms and 93% included measures of safety and/or efficacy as primary endpoints. Of 946 (18%) studies completed more than 2 years ago, only 11% had reported results and <7% had been published. In an area with a great need for evidence of safe and effective therapies, the low publication rate of completed studies incorporating elements of high-quality trial design is concerning. The sources of this trend should be closely investigated. © 2013, The American College of Clinical Pharmacology.

Rationale for the tinnitus retraining therapy trial

PubMed Central

Formby, Craig; Scherer, Roberta

2013-01-01

The Tinnitus Retraining Therapy Trial (TRTT) is a National Institutes of Health-sponsored, multi-centered, placebo-controlled, randomized trial evaluating the efficacy of tinnitus retraining therapy (TRT) and its component parts, directive counseling and sound therapy, as treatments for subjective debilitating tinnitus in the military. The TRTT will enroll 228 individuals at an allocation ratio of 1:1:1 to: (1) directive counseling and sound therapy using conventional sound generators; (2) directive counseling and placebo sound generators; or (3) standard of care as administered in the military. Study centers include a Study Chair’s Office, a Data Coordinating Center, and six Military Clinical Centers with treatment and data collection standardized across all clinics. The primary outcome is change in Tinnitus Questionnaire (TQ) score assessed longitudinally at 3, 6, 12, and 18-month follow-up visits. Secondary outcomes include: Change in TQ sub-scales, Tinnitus Handicap Inventory, Tinnitus Functional Index, and TRT interview visual analog scale; audiometric and psychoacoustic measures; and change in quality of life. The TRTT will evaluate TRT efficacy by comparing TRT (directive counseling and conventional sound generators) with standard of care; directive counseling by comparing directive counseling plus placebo sound generators versus standard of care; and sound therapy by comparing conventional versus placebo sound generators. We hypothesize that full TRT will be more efficacious than standard of care, directive counseling and placebo sound generators more efficacious than standard of care, and conventional more efficacious than placebo sound generators in habituating the tinnitus awareness, annoyance, and impact on the study participant’s life. PMID:23571304

Determining the Primary Endpoint for a Stimulant Abuse Trial: Lessons Learned from STRIDE (CTN 0037)

PubMed Central

Trivedi, Madhukar H.; Greer, Tracy L.; Potter, Jennifer Sharpe; Grannemann, Bruce D.; Nunes, Edward V.; Rethorst, Chad; Warden, Diane; Ring, Kolette M.; Somoza, Eugene

2012-01-01

Background No consensus is available for identifying the best primary outcome for substance abuse trials. While abstinence is the most desirable outcome for substance use interventions, a wide variety of other endpoints have been used to evaluate efficacy trials. Objectives This report provides a framework for determining an optimal primary endpoint and the relevant measurement approach for substance use disorder treatment trials. The framework was developed based on a trial for stimulant abuse using exercise as an augmentation treatment, delivered within the NIDA Clinical Trials Network. The use of a common primary endpoint across trials will facilitate comparisons of treatment efficacy. Methods Primary endpoint options in existing substance abuse studies were evaluated. This evaluation included surveys of the literature for endpoints and measurement approaches, followed by assessment of endpoint choices against study design issues, population characteristics, tests of sensitivity and tests of clinical meaningfulness. Conclusion We concluded that the best current choice for a primary endpoint is percent days abstinent, as measured by the Time Line Follow Back (TLFB) interview conducted three times a week with recall aided by a take-home Substance Use Diary. To further improve the accuracy of the self-reported drug use, an algorithm will be applied to reconcile the results from the TLFB with the results of qualitative urine drug screens. Scientific Significance There is a need for a standardized endpoint in this field to allow for comparison across treatment studies, and we suggest that the recommended endpoint be considered for use in this field. PMID:21854276

Combination Immunotherapy in Non-small Cell Lung Cancer.

PubMed

Marmarelis, Melina E; Aggarwal, Charu

2018-05-08

Checkpoint blockade has changed the treatment landscape in non-small cell lung cancer (NSCLC), but single-agent approaches are effective for only a select subset of patients. Here, we will review the evidence for combination immunotherapies in NSCLC and the clinical data evaluating the efficacy of this approach. Clinical trials evaluating combination PD-1 and CTLA-4 blockade as well as PD-1 in combination with agents targeting IDO1, B7-H3, VEGF, and EGFR show promising results. Additional studies targeting other immune pathways like TIGIT, LAG-3, and cellular therapies are ongoing. Combination immunotherapy has the potential to improve outcomes in NSCLC. Data from early clinical trials is promising and reveals that these agents can be administered together safely without a significant increase in toxicity. Further studies are needed to evaluate their long-term safety and efficacy and to determine appropriate patient selection.

Rituximab in systemic lupus erythematosus and lupus nephritis.

PubMed

Beckwith, Hannah; Lightstone, Liz

2014-01-01

Treatment options for systemic lupus erythematosus (SLE) and lupus nephritis (LN) have high associated morbidity and mortality. Side effects, particularly from long-term corticosteroid usage, limit patient adherence, with subsequent impacts on treatment efficacy. In addition, a subset of patients with SLE/LN fails to respond to current standard immunotherapy. There is an urgent need to develop steroid-sparing treatment regimens as well as novel therapies for the management of refractory disease. Rituximab is a chimeric mouse/human monoclonal antibody directed against the B cell CD20 receptor. It has been used in the treatment of non-Hodgkin's lymphoma for over 30 years and has an excellent safety profile. Recent work has demonstrated a role for B cell depletion therapy in the management of autoimmune disease, and the efficacy of rituximab in many observational studies in SLE and LN has been noted. Unfortunately, two large randomised controlled trials evaluating rituximab for the treatment of renal and non-renal lupus failed to meet their primary endpoints. Reasons for this have been discussed extensively within the medical community with a general consensus that trial design (steroid use, trial size and endpoints used) was the principal reason for the failures. Despite the lack of trial evidence, clinical experience means many physicians firmly believe in the value of rituximab in SLE/LN treatment and have continued to use it in their clinical practice. Recent work has demonstrated the efficacy of rituximab as a steroid-sparing agent and as an alternative therapeutic option for refractory SLE/LN. There are two further rituximab randomised controlled trials planned/started in LN – one using a steroid-minimising regimen with rituximab for induction and one evaluating rituximab for LN refractory to 6 months standard of care treatment. Rituximab remains a problematic drug in lupus and LN – it is a biologically plausible agent with a huge amount of supportive anecdotal clinical data. Yet the completed trials have been negative to date despite clinical experience strongly suggesting efficacy. It is hoped that the two new trials will determine the role for rituximab, at least in LN. © 2014 S. Karger AG, Basel.

Study protocol for a pragmatic randomised controlled trial evaluating efficacy of a smoking cessation e-'Tabac Info Service': ee-TIS trial.

PubMed

Cambon, L; Bergman, P; Le Faou, Al; Vincent, I; Le Maitre, B; Pasquereau, A; Arwidson, P; Thomas, D; Alla, F

2017-02-24

A French national smoking cessation service, Tabac Info Service, has been developed to provide an adapted quitline and a web and mobile application involving personalised contacts (eg, questionnaires, advice, activities, messages) to support smoking cessation. This paper presents the study protocol of the evaluation of the application (e-intervention Tabac Info Service (e-TIS)). The primary objective is to assess the efficacy of e-TIS. The secondary objectives are to (1) describe efficacy variations with regard to users' characteristics, (2) analyse mechanisms and contextual conditions of e-TIS efficacy. The study design is a two-arm pragmatic randomised controlled trial including a process evaluation with at least 3000 participants randomised to the intervention or to the control arm (current practices). Inclusion criteria are: aged 18 years or over, current smoker, having completed the online consent forms, possessing a mobile phone with android or apple systems and using mobile applications, wanting to stop smoking sooner or later. The primary outcome is the point prevalence abstinence of 7 days at 6 months later. Data will be analysed in intention to treat (primary) and per protocol analyses. A logistic regression will be carried out to estimate an OR (95% CI) for efficacy. A multivariate multilevel analysis will explore the influence on results of patients' characteristics (sex, age, education and socioprofessional levels, dependency, motivation, quit experiences) and contextual factors, conditions of use, behaviour change techniques. The study protocol was reviewed by the ethical and deontological institutional review board of the French Institute for Public Health Surveillance on 18 April 2016. The findings of this study will allow us to characterise the efficacy of e-TIS and conditions of its efficacy. These findings will be disseminated through peer-reviewed articles. NCT02841683; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Design of a single-arm clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence in Japan: the ADRESU study protocol.

PubMed

Shimizu, Shinobu; Yamamoto, Tokunori; Nakayama, Shinobu; Hirakawa, Akihiro; Kuwatsuka, Yachiyo; Funahashi, Yasuhito; Matsukawa, Yoshihisa; Takanari, Keisuke; Toriyama, Kazuhiro; Kamei, Yuzuru; Narimoto, Kazutaka; Yamanishi, Tomonori; Ishizuka, Osamu; Mizuno, Masaaki; Gotoh, Momokazu

2017-09-25

Male stress urinary incontinence is a prevalent condition after radical prostatectomy. While the standard recommendation for the management of urine leakage is pelvic floor muscle training, its efficacy is still unsatisfactory. Therefore, we have focused on regenerative therapy, which consists of administering a periurethral injection of autologous regenerative cells from adipose tissue, separated using the Celution® system. Based on an interim data analysis of our exploratory study, we confirmed the efficacy and acceptable safety profile of this treatment. Accordingly, we began discussions with Japanese regulatory authorities regarding the development of this therapy in Japan. The Ministry of Health, Labour and Welfare suggested that we implement a clinical trial of a new medical device based on the Pharmaceutical Affaires Act in Japan. Next, we discussed the design of this investigator-initiated clinical trial (the ADRESU study) aimed at evaluating the efficacy and safety of this therapy, in a consultation meeting with the Pharmaceuticals and Medical Device Agency. The ADRESU study is an open-label, multi-center, single-arm study involving a total of 45 male stress urinary incontinence patients with mild-to-moderate urine leakage persisting more than 1 year after prostatectomy, in spite of behavioral and pharmacological therapies. The primary endpoint is the rate of patients at 52 weeks with improvement of urine leakage volume defined as a reduction from baseline greater than 50% by 24-h pad test. Our specific hypothesis is that the primary endpoint result will be higher than a pre-specified threshold of 10%. The ADRESU study is the first clinical trial of regenerative treatment for stress urinary incontinence by adipose-derived regenerative cells using the Celution® system based on the Japanese Pharmaceutical Affaires Act. We will evaluate the efficacy and safety in this trial to provide an adequate basis for marketing approval with the final objective of making this novel therapy widely available for Japanese patients. This trial was registered at the University Hospital Medical information Network Clinical Trial Registry (UMIN-CTR Unique ID: UMIN000017901 ; Registered July 1, 2015) and at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02529865 ; Registered August 18, 2015).

Treatment of canine visceral leishmaniasis by the vaccine Leish-111f+MPL-SE.

PubMed

Trigo, Joelma; Abbehusen, Melissa; Netto, Eduardo M; Nakatani, Maria; Pedral-Sampaio, Geraldo; de Jesus, Robson Silva; Goto, Yasuyuki; Guderian, Jeffrey; Howard, Randall F; Reed, Steven G

2010-04-26

Immunotherapy of canine visceral leishmaniasis (CVL) may provide an alternative to both marginally effective chemotherapy and undesired euthanasia of infected dogs and could have a great impact not only on animal welfare, but also on control of human disease. Therefore, we examined the potential immunotherapeutic efficacy of the subunit vaccine Leish-111f+MPL-SE, which has undergone rigorous preclinical testing and been demonstrated safe in human clinical trials. Two separate trials were performed in Salvador, Brazil, to evaluate the vaccine for therapeutic efficacy against CVL caused by natural infection: an Open Trial and a Blinded Trial. In the Open Trial 59 dogs with clinically active CVL were sequentially allocated to four groups: group 1 received Leish-111f+MPL-SE; group 2 was treated with Glucantime; group 3 received a combination of the vaccine and Glucantime; and group 4 was given no treatment. At the 6-month assessment, the 13 non-treated dogs had either died or showed no clinical improvement. In contrast, most dogs in groups 1-3 showed initial improvement (100%, 80%, and 92%, respectively). Upon evaluation for a mean of 36 months after therapy, the following cure rates were observed: 75% for group 1 dogs (exact 95% confidence interval [CI] 43-95%), 64% for group 2 dogs (exact 95% CI 31-89%), and 50% for group 3 dogs (exact 95% CI 19-81%). Therapeutic efficacy of the Leish-111f+MPL-SE vaccine was reconfirmed in a subsequent Blinded Trial. The vaccine was effective for mild cases of CVL and was compromised in dogs with severe disease. Although further studies are required to understand mechanisms of action, the Leish-111f+MPL-SE vaccine is a promising tool to control VL in both dogs and humans. Copyright 2010 Elsevier Ltd. All rights reserved.

Investigation of the Study Characteristics Affecting Clinical Trial Quality Using the Protocol Deviations Leading to Exclusion of Subjects From the Per Protocol Set Data in Studies for New Drug Application: A Retrospective Analysis.

PubMed

Kohara, Norihito; Kaneko, Masayuki; Narukawa, Mamoru

2018-01-01

The concept of the risk-based approach has been introduced as an effort to secure the quality of clinical trials. In the risk-based approach, identification and evaluation of risk in advance are considered important. For recently completed clinical trials, we investigated the relationship between study characteristics and protocol deviations leading to the exclusion of subjects from Per Protocol Set (PPS) efficacy analysis. New drugs approved in Japan in the fiscal year 2014-2015 were targeted in the research. The reasons for excluding subjects from the PPS efficacy analysis were described in 102 trials out of 492 in the summary of new drug application documents, which was publicly disclosed after the drug's regulatory approval. The author extracted these reasons along with the numbers of the cases and the study characteristics of each clinical trial. Then, the direct comparison, univariate regression analysis, and multivariate regression analysis was carried out based on the exclusion rate. The study characteristics for which exclusion of subjects from the PPS efficacy analysis were frequently observed was multiregional clinical trials in study region; inhalant and external use in administration route; Anti-infective for systemic use; Respiratory system, Dermatologicals, and Nervous system in therapeutic drug under the Anatomical Therapeutic Chemical Classification. In the multivariate regression analysis, the clinical trial variables of inhalant, Respiratory system, or Dermatologicals were selected as study characteristics leading to a higher exclusion rate. The characteristics of the clinical trial that is likely to cause protocol deviations that will affect efficacy analysis were suggested. These studies should be considered for specific attention and priority observation in the trial protocol or its monitoring plan and execution, such as a clear description of inclusion/exclusion criteria in the protocol, development of training materials to site staff, and/or trial subjects as specific risk-alleviating measures.

Defining, Designing, Implementing, and Evaluating Phase 4 HIV Prevention Effectiveness Trials for Vulnerable Populations

PubMed Central

Kelly, Jeffrey A.; Spielberg, Freya; McAuliffe, Timothy L.

2008-01-01

Summary The efficacy of behavioral HIV prevention interventions has been convincingly demonstrated in a large number of randomized controlled phase 3 research outcome trials. Little research attention has been directed toward studying the effectiveness of the same interventions when delivered by providers to their own clients or community members, however. This article argues for the need to conduct phase 4 effectiveness trials of HIV prevention interventions that have been found efficacious in the research arena. Such trials can provide important information concerning the impact of interventions when applied in heterogeneous “real-world” circumstances. This article raises design issues and methodologic questions that need to be addressed in the conduct of phase 4 trials of behavioral interventions. These issues include the selection and training of service providers engaged in such trials, maintenance of fidelity to intervention protocol in provider-delivered interventions, determination of intervention core elements versus aspects that require tailoring, selection of relevant phase 4 study outcomes, interpretation of findings indicative of field effectiveness, sustainability, and other aspects of phase 4 trial design. PMID:18301131

Safety evaluation of trelagliptin in the treatment of Japanese type 2 diabetes mellitus patients.

PubMed

Kaku, Kohei

2017-11-01

Trelagliptin is a novel, long-acting dipeptidyl peptidase-4 (DPP-4) inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM) in japan. The safety and efficacy of trelagliptin has been evaluated in three published clinical trials to date: one phase II and two phase III studies. As trelagliptin only requires dosing once per week, this new agent has the potential to improve compliance and subsequently, glycaemic control, in patients with T2DM. Areas covered: This article reviews the available safety data for trelagliptin from published clinical trials, and evaluates the published safety profile relative to competitor once-daily and once-weekly DPP-4 inhibitors. Expert opinion: Clinical trial data to date suggest that trelagliptin is a safe and efficacious medication with a similar safety profile to once-daily DPP-4 inhibitors, and to the once-weekly DPP-4 inhibitor, omarigliptin. Trelagliptin is well tolerated when given alone, and in combination with other anti-diabetic medications. An advantage of trelagliptin over existing once-daily DPP-4 inhibitors is the decrease of dosing frequency, rather than once-daily. No specific, serious adverse events have been reported for trelagliptin in published clinical trials, making it an attractive alternative to other DPP-4 inhibitors.

The E Sibling Project - exploratory randomised controlled trial of an online multi-component psychoeducational intervention for siblings of individuals with first episode psychosis.

PubMed

Sin, Jacqueline; Henderson, Claire; Pinfold, Vanessa; Norman, Ian

2013-04-26

Siblings of individuals with first episode psychosis are natural partners to promote service users' recovery and are themselves vulnerable to mental ill health due to the negative impact of psychosis within the family. This study aims to develop and undertake a preliminary evaluation of the efficacy of an online multi-component psychoeducational intervention for siblings of individuals with first episode psychosis. The impetus for the intervention arose from siblings' expressed needs for peer support and information on psychosis, coping and management strategies for common symptoms and ways to promote recovery. The project design draws on the Medical Research Council framework for the design and evaluation of complex interventions. Mixed methods comprising collection of qualitative focus group data, systematic review and expert advisory group consultation are used to develop the theoretical basis for and design of the intervention. This protocol focuses on the modelling and piloting phase which uses a randomised controlled trial with factorial design to test the efficacy of the intervention. Outcome data on participants' mental wellbeing, knowledge, perceived self-efficacy and experiences of caregiving will be assessed at baseline, at end of the intervention (10 weeks later) and at 10 week follow-up. In addition, a post-intervention semi-structured interview with 20% of the participants will explore their experiences and acceptability of the intervention. This multi-component online psychoeducational intervention aims to enhance siblings' knowledge about psychosis and their coping capacity, thus potentially improving their own mental wellbeing and promoting their contribution to service users' recovery. The factorial design randomised controlled trial with a supplementary process evaluation using semi-structured interviews and usage-monitoring will collect preliminary evidence of efficacy, feasibility and acceptability, as well as feedback about the barriers and strategies to using such an innovative resource. The RCT will provide data for estimating the likely effect size of the intervention on outcomes for siblings and inform the development of a definitive future trial. Trial registration: ISRCTN01416694.

The Efficacy of Massage in Reducing Nodule Formation After Poly-L-Lactic Acid Administration for Facial Volume Loss: A Randomized, Evaluator-Blinded Clinical Trial.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2016-11-01

The risk of nodule formation following poly-L-lactic acid (PLLA) injections for facial volume loss is well known. Traditionally, post-treatment massage according to the 5-5-5 rule (5 times per day for 5 minutes for 5 days) has been applied to mitigate this risk. However, such a regimen may be onerous for patient compliance. Using currently accepted injection technique and product dilution, the efficacy of massage for nodule prevention has never been formally evaluated. To evaluate the efficacy of massage in reducing the incidence of nodule formation post-PLLA injection. After obtaining informed consent, 20 subjects with facial lipoatrophy were enrolled in this randomized, evaluator-blinded clinical trial. Each subject was treated with 1 vial of PLLA each month for 3 months. Vials were diluted with 1 mL of 1% lidocaine and 7 ml of bacteriostatic water, shaken with a vortex and refrigerated for 24 to 48 hours before injection. Ten subjects were instructed to massage the treated areas according to the 5-5-5 rule and 10 subjects did not perform any massage post-treatment. Six-month follow-up data were collected for treatment efficacy and adverse events. No nodules were reported by subjects or detected by the blinded evaluator regardless of massage status. Significant improvements in facial lipoatrophy were detected 1, 3, and 6 months after the final treatment session and were not statistically different between the 2 groups. Using currently recommended guidelines for product preparation and injection, the application of massage post-PLLA facial treatment does not have a significant impact on nodule formation or treatment efficacy.

An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation.

PubMed

Perkins, Kenneth A; Lerman, Caryn

2014-01-01

Initial screening of new medications for potential efficacy (i.e., Food and Drug Administration (FDA) early phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing. This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested as model drugs, in three separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil. This crossover procedure showed sensitivity (increased days of abstinence) during week-long "practice" quit attempts with each of the active cessation medications (positive controls) versus placebo, but not with modafinil (negative control) versus placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e., already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation). A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction.

Peer-Facilitated Discrete Trial Training for Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Young, K. Richard; Radley, Keith C.; Jenson, William R.; West, Richard P.; Clare, Susan K.

2016-01-01

In 2 studies, we evaluated the feasibility and efficacy of peer-mediated, school-based discrete trial training (DTT) for students with autism spectrum disorder (ASD). In the first, 6 typically developing elementary-age students were trained to use DTT procedures to teach target academic skills to 3 students with ASD who had been educated in a…

Cognitive-Behavioral Therapy for Anxiety Disordered Youth: A Randomized Clinical Trial Evaluating Child and Family Modalities

ERIC Educational Resources Information Center

Kendall, Philip C.; Hudson, Jennifer L.; Gosch, Elizabeth; Flannery-Schroeder, Ellen; Suveg, Cynthia

2008-01-01

This randomized clinical trial compared the relative efficacy of individual (child) cognitive-behavioral therapy (ICBT), family cognitive-behavioral therapy (FCBT), and a family-based education/support/attention (FESA) active control for treating anxiety disordered youth ages 7-14 years (M = 10.27). Youth (N = 161; 44% female; 85% Caucasian, 9%…

Venlafaxine ER for the Treatment of Pediatric Subjects with Depression: Results of Two Placebo-Controlled Trials

ERIC Educational Resources Information Center

Emslie, Graham J.; Findling, Robert L.; Yeung, Paul P.; Kunz, Nadia R.; Li, Yunfeng

2007-01-01

Objective: The safety, efficacy, and tolerability of venlafaxine extended release (ER) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter, randomized, double-blind, placebo-controlled trials conducted between October 1997 and August 2001. Method: Participants received venlafaxine ER (flexible dose,…

A Randomized Controlled Trial of a Behavioral Economic Supplement to Brief Motivational Interventions for College Drinking

ERIC Educational Resources Information Center

Murphy, James G.; Dennhardt, Ashley A.; Skidmore, Jessica R.; Borsari, Brian; Barnett, Nancy P.; Colby, Suzanne M.; Martens, Matthew P.

2012-01-01

Objective: Behavioral economic theory suggests that a reduction in substance use is most likely when there is an increase in rewarding substance-free activities. The goal of this randomized controlled clinical trial was to evaluate the incremental efficacy of a novel behavioral economic supplement (Substance-Free Activity Session [SFAS]) to a…

A Crossover Trial Evaluating an Educational-Behavioral Joint Protection Programme for People with Rheumatoid Arthritis.

ERIC Educational Resources Information Center

Hammond, A.; Lincoln, N.; Sutcliffe, L.

1999-01-01

Joint protection, a self-management technique taught to people with rheumatoid arthritis, was used in a group education program. A crossover trial (N=35) was conducted. No significant changes in measures of pain, functional disability, grip strength, self-efficacy or helplessness occurred post-education, although this may have been due to the…

Efficacy of Self-Regulated Strategy Development Instruction for Developing Writers with and without Disabilities in Rural Schools: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Mason, Linda H.; Cramer, Anne Mong; Garwood, Justin D.; Varghese, Cheryl; Hamm, Jill; Murray, Allen

2017-01-01

A workshop with virtual consultation practice-based professional development model for self-regulated strategy development persuasive writing instruction was evaluated in a randomized controlled trial. Nineteen general education teachers and 564 Grade 5 and 6 students in 16 low-wealth rural schools participated. Following training, teachers…

Cognitive enhancement treatments for bipolar disorder: A systematic review and methodological recommendations.

PubMed

Miskowiak, Kamilla W; Carvalho, André F; Vieta, Eduard; Kessing, Lars V

2016-10-01

Cognitive dysfunction is an emerging treatment target in bipolar disorder (BD). Several trials have assessed the efficacy of novel pharmacological and psychological treatments on cognition in BD but the findings are contradictory and unclear. A systematic search following the PRISMA guidelines was conducted on PubMed and PsychInfo. Eligible articles reported randomized, controlled or open-label trials investigating pharmacological or psychological treatments targeting cognitive dysfunction in BD. The quality of the identified randomized controlled trials (RCTs) was evaluated with the Cochrane Collaboration's Risk of Bias tool. We identified 19 eligible studies of which 13 were RCTs and six were open-label or non-randomized studies. The findings regarding efficacy on cognition were overall disappointing or preliminary, possibly due to several methodological challenges. For the RCTs, the risk of bias was high in nine cases, unclear in one case and low in three cases. Key reasons for the high risk of bias were lack of details on the randomization process, suboptimal handling of missing data and lack of a priori priority between cognition outcomes. Other challenges were the lack of consensus on whether and how to screen for cognitive impairment and on how to assess efficacy on cognition. In conclusion, methodological problems are likely to impede the success rates of cognition trials in BD. We recommend adherence to the CONSORT guidelines for RCTs, screening for cognitive impairment before inclusion of trial participants and selection of one primary cognition outcome. Future implementation of a 'neurocircuitry-based' biomarker model to evaluate neural target engagement is warranted. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Pharmacologic Treatment of Repetitive Behaviors in Autism Spectrum Disorders: Evidence of Publication Bias

PubMed Central

Volkmar, Fred R.; Bloch, Michael H.

2012-01-01

OBJECTIVE: The goal of this study was to examine the efficacy of serotonin receptor inhibitors (SRIs) for the treatment of repetitive behaviors in autism spectrum disorders (ASD). METHODS: Two reviewers searched PubMed and Clinicaltrials.gov for randomized, double-blind, placebo-controlled trials evaluating the efficacy of SRIs for repetitive behaviors in ASD. Our primary outcome was mean improvement in ratings scales of repetitive behavior. Publication bias was assessed by using a funnel plot, the Egger’s test, and a meta-regression of sample size and effect size. RESULTS: Our search identified 5 published and 5 unpublished but completed trials eligible for meta-analysis. Meta-analysis of 5 published and 1 unpublished trial (which provided data) demonstrated a small but significant effect of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.22 [95% confidence interval: 0.07–0.37], z score = 2.87, P < .005). There was significant evidence of publication bias in all analyses. When Duval and Tweedie's trim and fill method was used to adjust for the effect of publication bias, there was no longer a significant benefit of SRI for the treatment of repetitive behaviors in ASD (standardized mean difference: 0.12 [95% confidence interval: –0.02 to 0.27]). Secondary analyses demonstrated no significant effect of type of medication, patient age, method of analysis, trial design, or trial duration on reported SRI efficacy. CONCLUSIONS: Meta-analysis of the published literature suggests a small but significant effect of SRI in the treatment of repetitive behaviors in ASD. This effect may be attributable to selective publication of trial results. Without timely, transparent, and complete disclosure of trial results, it remains difficult to determine the efficacy of available medications. PMID:22529279

Efficacy and safety of novel antipsychotics: a critical review.

PubMed

Balestrieri, Matteo; Vampini, Claudio; Bellantuono, Cesario

2000-10-01

Efficacy and safety of novel antipsychotic (AP) drugs (amisulpride, olanzapine, quetiapine, ziprasidone and zotepine) have been reviewed. Data on their antipsychotic efficacy and side effects profile have been evaluated only on the basis of controlled trials so far published. Overall, all these drugs have shown an antipsychotic efficacy on positive symptoms of schizophrenia similar to that of the conventional AP drugs. On negative symptoms, all novel AP drugs, except quetiapine and ziprasidone, demonstrated a better efficacy than haloperidol. Long-term efficacy of these AP drugs in the maintenance treatment of schizophrenia needs to be explored by further, better-designed, epidemiological studies. The safety profile shows that the novel AP drugs are generally well-tolerated and induce significantly less acute extrapyramidal side effects in comparison with haloperidol. Some methodological flaws in the experimental design of the clinical trials analysed are discussed. Although these novel AP drugs have potential clinical advantages, a number of relevant questions still remain to be addressed, in order to establish the impact of these drugs in the overall treatment of schizophrenia. Copyright 2000 John Wiley & Sons, Ltd.

Planning for pre-exposure prophylaxis to prevent HIV transmission: challenges and opportunities

PubMed Central

2010-01-01

There are currently several ongoing or planned trials evaluating the efficacy of pre-exposure prophylaxis (PrEP) as a preventative approach to reducing the transmission of HIV. PrEP may prove ineffective, demonstrate partial efficacy, or show high efficacy and have the potential to reduce HIV infection in a significant way. However, in addition to the trial results, it is important that issues related to delivery, implementation and further research are also discussed. As a part of the ongoing discussion, in June 2009, the Bill & Melinda Gates Foundation sponsored a Planning for PrEP conference with stakeholders to review expected trial results, outline responsible educational approaches, and develop potential delivery and implementation strategies. The conference reinforced the need for continued and sustained dialogue to identify where PrEP implementation may fit best within an integrated HIV prevention package. This paper identifies the key action points that emerged from the Planning for PrEP meeting. PMID:20624303

[Randomized, controlled clinical trials with observational follow-up investigations for evaluating efficacy of antihyperglycaemic treatment. I. Main results of the studies].

PubMed

Jermendy, György

2018-04-01

The effect of antihyperglycaemic (antidiabetic) treatment on the late diabetic complications is one of the most important research areas in clinical diabetology. The relationship between glycaemic control and late micro- and macrovascular complications was highlighted by the results of the DCCT (Diabetes Control and Complications Trial) with type 1 and by the UKPDS (United Kingdom Prospective Diabetes Study) with type 2 diabetic patients. In these studies, observational follow-up investigations were also performed after the close-out of the randomized phase of the trial. In addition to these landmark studies, other randomized, controlled efficacy trials were also performed with observational follow-up investigations resulting in the development of the concept of metabolic memory or metabolic legacy. In this article, the main results of the studies are summarized. Orv Hetil. 2018; 159(15): 575-582.

Primary analysis for clinical efficacy of immunotherapy in patients with pancreatic cancer.

PubMed

Chen, Linghua; Zhang, Xiaoyan

2016-02-01

Immunotherapy is an important treatment for pancreatic cancer (PC) patients. To evaluate the therapeutic efficacy of immunotherapy in the treatment of PC, we performed a systemic review and meta-analysis of the relevant published clinical trials, collectively referred to as DC, DC-CIK, LAK, NK and GM-CSF secreting PC cell lines.  A total of 413 patients in 11 eligible trials with PC were selected for the present meta-analysis. The estimated pooled overall survival showed a significant improvement for PC patients who received immunotherapy compared with nonimmunotherapy. The lymphocyte subsets, immune cytokine levels and serum cancer markers in the peripheral blood of PC patients were significantly improved after immunotherapy. The results showed that immunotherapy can improve the efficacy of the treatment of PC patients.

Field efficacy of eprinomectin against the sucking louse Haematopinus asini on naturally infested donkeys.

PubMed

Veneziano, Vincenzo; Galietti, Alfredo; Mariani, Ugo; Di Loria, Antonio; Piantedosi, Diego; Neola, Benedetto; Guccione, Jacopo; Gokbulut, Cengiz

2013-08-01

A trial was conducted to assess the efficacy of eprinomectin (EPR) against the sucking louse Haematopinus asini on naturally infested donkeys. Parasitological investigations were performed on fifteen animals. On day 0, donkeys received EPR pour-on at the manufacturer's recommended cattle dose. Louse counts were performed on days -1, 7, 14, 21, 28, 35, 42, 49 and 56 at seven predilection sites on the skin of each donkey. EPR was completely effective (100%) from day 7, until the end of the study. Clinically no adverse reactions were observed in any of donkeys treated. EPR was considered to be 100% effective against H. asini. This is the first trial to evaluate the efficacy of EPR against a natural louse infestation in donkeys. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo- controlled trial

PubMed Central

Mao, Jun J; Li, Qing S.; Soeller, Irene; Xie, Sharon X; Amsterdam, Jay D.

2014-01-01

Background Rhodiola rosea (R. rosea), a botanical of both western and traditional Chinese medicine, has been used as a folk remedy for improving stamina and reducing stress. However, few controlled clinical trials have examined the safety and efficacy of R. rosea for the treatment of major depressive disorder (MDD). This study seeks to evaluate the safety and efficacy of R. rosea in a 12-week, randomized, double-blind, placebo-controlled, parallel group study design. Methods / Design Subjects with MDD not receiving antidepressant therapy will be randomized to either R. rosea extract 340–1,360 mg daily; sertraline 50–200 mg daily, or placebo for 12 weeks. The primary outcome measure will be change over time in the mean 17-item Hamilton Depression Rating score. Secondary outcome measures will include safety and quality of life ratings. Statistical procedures will include mixed-effects models to assess efficacy for primary and secondary outcomes. Discussion This study will provide valuable preliminary information on the safety and efficacy data of R. rosea versus conventional antidepressant therapy of MDD. It will also inform additional hypotheses and study design of future, fully powered, phase III clinical trials with R. rosea to determine its safety and efficacy in MDD. PMID:25610752

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

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

PubMed Central

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

2012-01-01

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

Evaluation of Control Points in Youngstock and Adult Dairy Cow Management to Control Transmission of Mycobacterium avium subsp. paratuberculosis

USDA-ARS?s Scientific Manuscript database

Goal Complete a series of controlled on-farm trials to critically evaluate the efficacy and cost-benefit of commonly recommended management practices for reducing the transmission of Mycobacterium avium subsp. paratuberculosis (Map) in infected herds. Objective 1. Evaluate the effect of maternity...

Impact of evergreening on patients and health insurance: a meta analysis and reimbursement cost analysis of citalopram/escitalopram antidepressants

PubMed Central

2012-01-01

Background "Evergreening" refers to the numerous strategies whereby owners of pharmaceutical products use patent laws and minor drug modifications to extend their monopoly privileges on the drug. We aimed to evaluate the impact of evergreening through the case study of the antidepressant citalopram and its chiral switch form escitalopram by evaluating treatment efficacy and acceptability for patients, as well as health insurance costs for society. Methods To assess efficacy and acceptability, we performed meta-analyses for efficacy and acceptability. We compared direct evidence (meta-analysis of results of head-to-head trials) and indirect evidence (adjusted indirect comparison of results of placebo-controlled trials). To assess health insurance costs, we analyzed individual reimbursement data from a representative sample of the French National Health Insurance Inter-regime Information System (SNIIR-AM) from 2003 to 2010, which allowed for projecting these results to the whole SNIIR-AM population (53 million people). Results In the meta-analysis of seven head-to-head trials (2,174 patients), efficacy was significantly better for escitalopram than citalopram (combined odds ratio (OR) 1.60 (95% confidence interval 1.05 to 2.46)). However, for the adjusted indirect comparison of 10 citalopram and 12 escitalopram placebo-controlled trials, 2,984 and 3,777 patients respectively, efficacy was similar for the two drug forms (combined indirect OR 1.03 (0.82 to 1.30)). Because of the discrepancy, we could not combine direct and indirect data (test of inconsistency, P = 0.07). A similar discrepancy was found for treatment acceptability. The overall reimbursement cost burden for the citalopram, escitalopram and its generic forms was 120.6 million Euros in 2010, with 96.8 million Euros for escitalopram. Conclusions The clinical benefit of escitalopram versus citalopram remains uncertain. In our case of evergreening, escitalopram represented a substantially high proportion of the overall reimbursement cost burden as compared with citalopram and the generic forms. PMID:23167972

Impact of evergreening on patients and health insurance: a meta analysis and reimbursement cost analysis of citalopram/escitalopram antidepressants.

PubMed

Alkhafaji, Ali A; Trinquart, Ludovic; Baron, Gabriel; Desvarieux, Moïse; Ravaud, Philippe

2012-11-20

"Evergreening" refers to the numerous strategies whereby owners of pharmaceutical products use patent laws and minor drug modifications to extend their monopoly privileges on the drug. We aimed to evaluate the impact of evergreening through the case study of the antidepressant citalopram and its chiral switch form escitalopram by evaluating treatment efficacy and acceptability for patients, as well as health insurance costs for society. To assess efficacy and acceptability, we performed meta-analyses for efficacy and acceptability. We compared direct evidence (meta-analysis of results of head-to-head trials) and indirect evidence (adjusted indirect comparison of results of placebo-controlled trials). To assess health insurance costs, we analyzed individual reimbursement data from a representative sample of the French National Health Insurance Inter-regime Information System (SNIIR-AM) from 2003 to 2010, which allowed for projecting these results to the whole SNIIR-AM population (53 million people). In the meta-analysis of seven head-to-head trials (2,174 patients), efficacy was significantly better for escitalopram than citalopram (combined odds ratio (OR) 1.60 (95% confidence interval 1.05 to 2.46)). However, for the adjusted indirect comparison of 10 citalopram and 12 escitalopram placebo-controlled trials, 2,984 and 3,777 patients respectively, efficacy was similar for the two drug forms (combined indirect OR 1.03 (0.82 to 1.30)). Because of the discrepancy, we could not combine direct and indirect data (test of inconsistency, P = 0.07). A similar discrepancy was found for treatment acceptability. The overall reimbursement cost burden for the citalopram, escitalopram and its generic forms was 120.6 million Euros in 2010, with 96.8 million Euros for escitalopram. The clinical benefit of escitalopram versus citalopram remains uncertain. In our case of evergreening, escitalopram represented a substantially high proportion of the overall reimbursement cost burden as compared with citalopram and the generic forms.

Tribendimidine and albendazole for treating soil-transmitted helminths, Strongyloides stercoralis and Taenia spp.: open-label randomized trial.

PubMed

Steinmann, Peter; Zhou, Xiao-Nong; Du, Zun-Wei; Jiang, Jin-Yong; Xiao, Shu-Hua; Wu, Zhong-Xing; Zhou, Hui; Utzinger, Jürg

2008-01-01

Tribendimidine is an anthelminthic drug with a broad spectrum of activity. In 2004 the drug was approved by Chinese authorities for human use. The efficacy of tribendimidine against soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) has been established, and new laboratory investigations point to activity against cestodes and Strongyloides ratti. In an open-label randomized trial, the safety and efficacy of a single oral dose of albendazole or tribendimidine (both drugs administered at 200 mg for 5- to 14-year-old children, and 400 mg for individuals > or = 15 years) against soil-transmitted helminths, Strongyloides stercoralis, and Taenia spp. were assessed in a village in Yunnan province, People's Republic of China. The analysis was on a per-protocol basis and the trial is registered with controlled-trials.com (number ISRCTN01779485). Both albendazole and tribendimidine were highly efficacious against A. lumbricoides and, moderately, against hookworm. The efficacy against T. trichiura was low. Among 57 individuals who received tribendimidine, the prevalence of S. stercoralis was reduced from 19.3% to 8.8% (observed cure rate 54.5%, p = 0.107), and that of Taenia spp. from 26.3% to 8.8% (observed cure rate 66.7%, p = 0.014). Similar prevalence reductions were noted among the 66 albendazole recipients. Taking into account "new" infections discovered at treatment evaluation, which were most likely missed pre-treatment due to the lack of sensitivity of available diagnostic approaches, the difference between the drug-specific net Taenia spp. cure rates was highly significant in favor of tribendimidine (p = 0.001). No significant adverse events of either drug were observed. Our results suggest that single-dose oral tribendimidine can be employed in settings with extensive intestinal polyparasitism, and its efficacy against A. lumbricoides and hookworm was confirmed. The promising results obtained with tribendimidine against S. stercoralis and Taenia spp. warrant further investigations. In a next step, multiple-dose schedules should be evaluated.

Efficacy of Continuing Education in Improving Pharmacists' Competencies for Providing Weight Management Service: Three-Arm Randomized Controlled Trial

ERIC Educational Resources Information Center

Sarayani, Amir; Rashidian, Arash; Gholami, Kheirollah; Torkamandi, Hassan; Javadi, Mohammadreza

2012-01-01

Introduction: Weight management is a new public health role for community pharmacists in many countries. Lack of expertise is one of the key barriers to counseling obese patients. We evaluated the comparative efficacy of three alternative continuing education (CE) meetings on weight management. Methods: We designed a randomized controlled trial…

Can Aidi injection restore cellular immunity and improve clinical efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy? A meta-analysis of 17 randomized controlled trials following the PRISMA guidelines.

PubMed

Xiao, Zheng; Wang, Chengqiong; Sun, Yongping; Li, Nana; Li, Jing; Chen, Ling; Yao, Xingsheng; Ding, Jie; Ma, Hu

2016-11-01

Aidi injection is an adjuvant chemotherapy drug commonly used in China. Can Aidi injection restore the cellular immunity and improve the clinical efficacy in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy? There is a lack of strong evidence to prove it. To further reveal it, we systematically evaluated all related studies. We collected all studies about the clinical efficacy and cellular immunity of Aidi injection plus platinum-based chemotherapy for NSCLC in Medline, Embase, Web of Science, China national knowledge infrastructure database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang, China biological medicine database (CBM) (established to June 2015), Cochrane Central Register of Controlled Trials (CCRCT) (June 2015), Chinese clinical trial registry, and US-clinical trials (June 2015). We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0), extracted data following the patient intervention control group outcomes principles and synthesized the data by meta-analysis. Seventeen (RCTs) with 1390 NSCLC patients were included, with general methodological quality in most trials. The merged relative risk (RR) values and their 95% CI of meta-analysis for objective response rate (ORR) and disease control rate (DCR) were as follows: 1.26 (1.12, 1.42) and 1.11(1.04, 1.17). The merged standardized mean difference (SMD) values and their 95% CI of meta-analysis for the percentage of CD3T cells, CD4T cells, CD8T cells, natural killer (NK) cells, and CD4/CD8 T cell ratio were as follows: 1.41, (0.89, 1.92), 1.59, (1.07, 2.11), 0.85, (0.38, 1.33), 1.64 (0.89, 2.39) and 0.91, (0.58, 1.24). Compared with platinum-based chemotherapy alone, all differences were statistically significant. These results might be overestimated or underestimated. Aidi injection plus platinum-based chemotherapy can improve the clinical efficacy of patients with NSCLC. Aidi injection could significantly restore the cellular immunity damaged by platinum-based chemotherapy. It may be an important tumor immune modulator and protector for patients with NSCLC treated with chemotherapy.

Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

PubMed

Delrieu, Isabelle; Leboulleux, Didier; Ivinson, Karen; Gessner, Bradford D

2015-03-24

Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist. Copyright © 2015 Elsevier Ltd. All rights reserved.

Laboratory evaluation of the predation efficacy of native Australian fish on Culex annulirostris (Diptera: Culicidae).

PubMed

Hurst, Timothy P; Brown, Michael D; Kay, Brian H

2004-09-01

The introduction and establishment of fish populations can provide long-term, cost-effective mosquito control in habitats such as constructed wetlands and ornamental lakes. The predation efficacy of 7 native Brisbane freshwater fish on 1st and 4th instars of the freshwater arbovirus vector Culex annulirostris was evaluated in a series of 24-h laboratory trials. The trials were conducted in 30-liter plastic carboys at 25+/-1 degrees C under a light:dark cycle of 14:10 h. The predation efficacy of native crimson-spotted rainbowfish Melanotaenia duboulayi (Melanotaeniidae), Australian smelt Retropinna semoni (Retropinnadae), Pacific blue-eye Pseudomugil signifer (Atherinidae), fly-specked hardyhead Craterocephalus stercusmuscarum (Atherinidae), firetail gudgeon Hypseleotris galii (Eleotridae), empire gudgeon Hypseleotris compressa (Eleotridae), and estuary perchlet Ambassis marianus (Ambassidae) was compared with the exotic eastern mosquitofish Gambusia holbrooki (Poeciliidae). This environmentally damaging exotic has been disseminated worldwide and has been declared noxious in Queensland. Melanotaenia duboulayi was found to consume the greatest numbers of both 1st and 4th instars of Cx. annulirostris. The predation efficacy of the remaining Australian native species was comparable with that of the exotic G. holbrooki. With the exception of A. marianus, the maximum predation rates of these native species were not statistically different whether tested individually or in a school of 6. Based on these data, M. duboulayi, H. compressa, and A. marianus warrant further investigation as biological control agents in pilot field trials.

The use of ginger (Zingiber officinale) for the treatment of pain: a systematic review of clinical trials.

PubMed

Terry, Rohini; Posadzki, Paul; Watson, Leala K; Ernst, Edzard

2011-12-01

  Zingiber officinale (Z. officinale), commonly known as ginger, has been widely used traditionally for a variety of medicinal purposes, one of which is for the treatment of pain. The aim of this systematic review was to evaluate the evidence from all human participant clinical trials that have assessed the efficacy of ginger for the treatment of any type of pain.   Following a protocol, multiple databases were sought using comprehensive search strategies for Z. officinale and pain together with a trial filter for randomized or controlled clinical trials. Trials testing the efficacy of Z. officinale, used as a sole oral treatment against a comparison condition in human adults suffering from any pain condition, were included.   Seven published articles, reporting a total of eight trials (481 participants), were included in the review. Six trials (two for osteoarthritis, one for dysmenorrhea, and three for experimentally induced acute muscle pain) found that the use of Z. officinale reduced subjective pain reports. The methodological quality of the included articles was variable. When assessed using the Jadad scale, which allows a score of between 0 and 5 to be given, included articles obtained Jadad ratings ranging from 2 to 5.   Due to a paucity of well-conducted trials, evidence of the efficacy of Z. officinale to treat pain remains insufficient. However, the available data provide tentative support for the anti-inflammatory role of Z. officinale constituents, which may reduce the subjective experience of pain in some conditions such as osteoarthritis. Further rigorous trials therefore seem to be warranted. Wiley Periodicals, Inc.

Efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II trial): study protocol for a randomized controlled trial.

PubMed

Tamura, Tomoyoshi; Hayashida, Kei; Sano, Motoaki; Onuki, Shuko; Suzuki, Masaru

2017-10-23

Hydrogen gas inhalation (HI) improved survival and neurological outcomes in an animal model of post-cardiac arrest syndrome (PCAS). The feasibility and safety of HI for patients with PCAS was confirmed in a pilot study. The objective of this study is to evaluate the efficacy of HI for patients with PCAS. The efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II) trial is an investigator-initiated, randomized, double-blind, placebo-controlled trial designed to enroll 360 adult comatose (Glasgow Coma Scale score < 8) patients who will be resuscitated following an out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized (1:1) to either the HI or control group. Patients in the HI group will inhale 2% hydrogen with 24% to 50% oxygen, and those in the control group will inhale 24% to 50% oxygen for 18 h after admission via mechanical ventilation. Multidisciplinary post-arrest care, including targeted temperature management (TTM) between 33 °C and 36 °C, will be provided in accordance with the latest guidelines. The primary outcome of interest is the 90-day neurological outcome, as evaluated using the Cerebral Performance Categories scale (CPC). The secondary outcomes of interest are the 90-day survival rate and other neurological outcomes. This study will provide 80% power to detect a 15% change in the proportion of patients with good neurological outcomes (CPCs of 1 and 2), from 50% to 65%, with an overall significance level of 0.05. The first multicenter randomized trial is underway to confirm the efficacy of HI on neurological outcomes in comatose out-of-hospital cardiac arrest survivors. Our study has the potential to address HI as an appealing and innovative therapeutic strategy for PCAS in combination with TTM. University Hospital Medical Information Network (UMIN), 000019820 . Registered on 17 November 2015.

Direct oral anticoagulants for extended thromboprophylaxis in medically ill patients: meta-analysis and risk/benefit assessment.

PubMed

Al Yami, Majed S; Kurdi, Sawsan; Abraham, Ivo

2018-01-01

Standard-duration (7-10 days) thromboprophylaxis with low molecular weight heparin, low dose unfractionated heparin, or fondaparinux in hospitalized medically ill patients is associated with ~50% reduction in venous thromboembolism (VTE) risk. However, these patients remain at high risk for VTE post-discharge. The direct oral anticoagulants (DOACs) apixaban, rivaroxaban and betrixaban have been evaluated for extended-duration (30-42 days) thromboprophylaxis in this population. We review the efficacy and safety results from the 3 pivotal trials of extended-duration DOAC thromboprophylaxis in medically ill patients. We performed a meta-analysis of these pivotal trials focusing on 6 VTE (efficacy) and three bleeding outcomes (safety). These results were integrated into a quantitative risk/benefit assessment. The trials evaluating extended-duration DOAC thromboprophylaxis in medically ill patients failed to establish clear efficacy and/or safety signals for each agent. Our meta-analysis shows that, as a class, DOACs have selective and partial extended-duration prophylactic activity in preventing VTE events. However, this is associated with a marked increase in the risk of various bleeding events. The risk/benefit analyses fail to show a consistent net clinical benefit of extended-duration DOAC prophylaxis in medically ill patients. At this time, the evidence of safe and effective extended-duration thromboprophylaxis with DOACs in this population is inconclusive.

Safety analysis of sofosbuvir and ledipasvir for treating hepatitis C.

PubMed

Fazel, Yousef; Lam, Brian; Golabi, Pegah; Younossi, Zobair

2015-08-01

The approval of sofosbuvir (SOF), a nucleotide analogue NS5B polymerase inhibitor, and ledipasvir (LDV), a NS5A inhibitor, marked a new chapter in IFN and ribavirin-free treatment of hepatitis C virus (HCV). This drug reduces adverse events associated with IFN therapy. The purpose of this paper is to evaluate the safety and efficacy of LDV/SOF. Clinical trials illustrating safety and efficacy of LDV/SOF are reviewed and compared to other IFN and ribavirin-free treatment options available. In trials enrolling more than 3000 patients, LDV/SOF is well tolerated with a good safety and side-effect profile in diverse cohorts, including previous direct-acting antiviral (DAA) treatment failures, liver transplant recipients, decompensated cirrhosis and HIV/HCV co-infection. As with all DAAs, the potential for drug-drug interactions must be carefully evaluated, as demonstrated by recent post-marketing reports of symptomatic bradycardia when LDV/SOF is co-administered with amiodarone. Currently, dose recommendations cannot be given for patients with advanced renal disease. Trials in this population are ongoing, more study is warranted. When surveying the DAA regimens available, efficacy, safety and tolerability of LDV/SOF is comparable or better, and LDV/SOF provides an option with convenient single-tablet, once daily, ribavirin-free dosing with relatively few significant drug-drug interactions.

Complementary and Alternative Medicine Treatments for Generalized Anxiety Disorder: Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Barić, Hrvoje; Đorđević, Veljko; Cerovečki, Ivan; Trkulja, Vladimir

2018-03-01

The objective was to evaluate efficacy/safety of complementary and alternative medicine (CAM) methods for generalized anxiety disorder (GAD) based on randomized controlled trials in adults. Data sources. Six electronic databases ("generalized anxiety (disorder)" and "randomized trial") and reference lists of identified publications were searched to March 2017. Eligibility: full-text publications (English, German language); CAM versus conventional treatment, placebo/sham or no treatment; GAD diagnosed according to standard criteria; and a validated scale for disease severity. Of the 6693 screened records, 32 were included (18 on biologically-based therapies, exclusively herbal preparations; eight on manipulative and body-based therapies; and three on alternative medical systems and three on mind-body therapies). Cochrane Collaboration methodology was used for quality assessment and data extraction. Direct comparisons of Kava Kava (Piper methysticum) extracts to placebo (4 quality trials, n = 233) were highly heterogeneous. Network meta-regression reduced heterogeneity and suggested a modest Kava effect [end-of-treatment Hamilton Anxiety scale score difference adjusted for baseline scores and trial duration: - 3.24 (95% CI - 6.65, 0.17; P = 0.059), Kava Kava 4 arms, n = 139; placebo 5 arms, n = 359]. Lavender (Lavandula angustifolia) extract (1 quality trial, 10 weeks, n = 523) and a combination of extracts of C. oxycantha, E. californica and magnesium (1 quality trial, 12 weeks, n = 264) were superior to placebo and balneotherapy was superior to paroxetine (1 quality trial, 8 weeks, n = 237) indicating efficacy. All other trials were small and/or of modest/low quality and/or lacked assay sensitivity. Safety reporting was poor. Evidence about efficacy/safety of most CAM methods in GAD is limited. Apparent efficacy of certain herbal preparations and body-based therapies requires further confirmation.

The Efficacy and Safety of Mainstream Medications for Patients With cDMARD-Naïve Rheumatoid Arthritis: A Network Meta-Analysis.

PubMed

Cai, Weiyan; Gu, Youyi; Cui, Huanqin; Cao, Yinyin; Wang, Xiaoliang; Yao, Yi; Wang, Mingyu

2018-01-01

Background: The mainstream medications for rheumatoid arthritis (RA) include conventional disease-modifying antirheumatic drugs (cDMARDs), which mostly are methotrexate (MTX), and biologic agents such as adalimumab (ADA), certolizumab (CZP), etanercept (ETN), golimumab (GOL), infliximab (IFX), and tocilizumab (TCZ). This network meta-analysis was aimed at evaluating the efficacy and safety of the medications above and interventions combining cDMARDs and biologic agents for patients with RA. Methods: PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched systematically for eligible randomized controlled trials (RCTs). Outcomes concerning efficacy and safety were evaluated utilizing odds ratios (ORs) and 95% credible intervals ( CrI ). The outcomes of efficacy would be evaluated through remission and American College of Rheumatology (ACR) scores. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment on each index. Results: A total of 20 RCTs with 9,047 patients were included, and the efficacy and safety of the concerning interventions for RA were evaluated. Compared with cDMARDs alone, TCZ+MTX, ETN+MTX, IFX+MTX, TCZ, and ADA+MTX showed significant statistical advantage on ACR20, ACR50, and ACR70. Apart from that, as for remission, TCZ+MTX, IFX+MTX, TCZ, and CZP+MTX performed better compared to cDMARDs alone. The SUCRA ranking also indicated that TCZ+MTX was the intervention with best ranking in the entire four efficacy indexes followed by ETX+MTX and IFX+MTX. However, there was no obvious difference among these medications compared with cDMARDs when it comes to safety, which need more specific studies on that. Conclusion: TCZ+MTX was potentially the most recommended combination of medications for RA due to its good performance in all outcomes of efficacy. ETX+MTX and IFX+MTX, which also performed well, could be introduced as alternative treatments. However, considering the adverse events, the treatments concerning should be introduced with caution.

Medical statistics and hospital medicine: the case of the smallpox vaccination.

PubMed

Rusnock, Andrea

2007-01-01

Between 1799 and 1806, trials of vaccination to determine its safety and efficacy were undertaken in hospitals in London, Paris, Vienna, and Boston. These trials were among the first instances of formal hospital evaluations of a medical procedure and signal a growing acceptance of a relatively new approach to medical practice. These early evaluations of smallpox vaccination also relied on descriptive and quantitative accounts, as well as probabilistic analyses, and thus occupy a significant, yet hitherto unexamined, place in the history of medical statistics.

Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.

PubMed

Talley, N J; Tack, J; Ptak, T; Gupta, R; Giguère, M

2008-06-01

Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD. Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life. The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591). In this population with FD, itopride did not show a difference in symptom response from placebo.

Likelihood-based methods for evaluating principal surrogacy in augmented vaccine trials.

PubMed

Liu, Wei; Zhang, Bo; Zhang, Hui; Zhang, Zhiwei

2017-04-01

There is growing interest in assessing immune biomarkers, which are quick to measure and potentially predictive of long-term efficacy, as surrogate endpoints in randomized, placebo-controlled vaccine trials. This can be done under a principal stratification approach, with principal strata defined using a subject's potential immune responses to vaccine and placebo (the latter may be assumed to be zero). In this context, principal surrogacy refers to the extent to which vaccine efficacy varies across principal strata. Because a placebo recipient's potential immune response to vaccine is unobserved in a standard vaccine trial, augmented vaccine trials have been proposed to produce the information needed to evaluate principal surrogacy. This article reviews existing methods based on an estimated likelihood and a pseudo-score (PS) and proposes two new methods based on a semiparametric likelihood (SL) and a pseudo-likelihood (PL), for analyzing augmented vaccine trials. Unlike the PS method, the SL method does not require a model for missingness, which can be advantageous when immune response data are missing by happenstance. The SL method is shown to be asymptotically efficient, and it performs similarly to the PS and PL methods in simulation experiments. The PL method appears to have a computational advantage over the PS and SL methods.

Renal denervation therapy for hypertension: pathways for moving development forward.

PubMed

White, William B; Galis, Zorina S; Henegar, Jeffrey; Kandzari, David E; Victor, Ronald; Sica, Domenic; Townsend, Raymond R; Turner, J Rick; Virmani, Renu; Mauri, Laura

2015-05-01

This scientific statement provides a summary of presentations and discussions at a cardiovascular Think Tank co-sponsored by the American Society of Hypertension (ASH), the United States Food and Drug Administration (FDA), and the National Heart, Lung, and Blood Institute (NHLBI) held in North Bethesda, Maryland, on June 26, 2014. Studies of device therapies for the treatment of hypertension are requested by regulators to evaluate their safety and efficacy during their development programs. Think Tank participants thought that important considerations in undertaking such studies were: (1) Preclinical assessment: how likely it is that both efficacy and safety data indicating benefit in humans will be obtained, and/or whether a plausible mechanism of action for efficacy can be identified; (2) Early human trial(s): the ability to determine that the device has an acceptable benefit-to-risk balance for its use in the intended patient population and without the influence of drug therapy during a short-term follow-up period; and (3) Pivotal Phase III trial(s): the ability to prove the effectiveness of the device in a broad population in which the trial can be made as non-confounded as possible while still allowing for the determination for benefits when added to antihypertensive therapies. Copyright © 2015 American Society of Hypertension. All rights reserved.

Does the rising placebo response impact antihypertensive clinical trial outcomes? An analysis of data from the Food and Drug Administration 1990-2016

PubMed Central

Fahl Mar, Kaysee; Schilling, Joshua; Brown, Walter A.

2018-01-01

Background Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension. Method For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms). Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures. Results Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018) and effect size (R2 = 0.013, p = 0.187) drug-placebo difference (R2 = 0.013, p = 0.182) and success rate (134/142, 94.4%) have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, p<0.001). Treatment arms are likely overpowered with sample sizes increasing over time (R2 = 0.387, p<0.0001) and stable, large effect sizes (0.78 ±0.37). The exploratory analysis of sample size, trial duration, baseline blood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877), antihypertensive-placebo differences (p = 0.752), or p-values (p = 0.963) but was correlated with antihypertensive response (R2 = 0.347, p<0.0001). Conclusions As hypothesized, this study shows that placebo response is increasing in clinical trials for hypertension without any evidence of this increase impacting trial outcomes. Attempting to control placebo response in clinical trials for hypertension may not be necessary for successful efficacy outcomes. In exploratory analysis, we noted that despite finding significant relationships, none of the trial or patient characteristics we examined offered a clear explanation of the rise in placebo and stability in outcome measures over time. Collectively, these data suggest that the phenomenon of increasing placebo response and stable efficacy outcomes may be a general trend, occurring across trials for various psychiatric and medical conditions with physiological and non-physiological endpoints. PMID:29489874

Safety and efficacy of adjunctive lacosamide among patients with partial-onset seizures in a long-term open-label extension trial of up to 8 years.

PubMed

Rosenfeld, William; Fountain, Nathan B; Kaubrys, Gintaras; Ben-Menachem, Elinor; McShea, Cindy; Isojarvi, Jouko; Doty, Pamela

2014-12-01

Long-term (up to 8 years of exposure) safety and efficacy of the antiepileptic drug lacosamide was evaluated in this open-label extension trial (SP615 [ClinicalTrials.gov identifier: NCT00552305]). Patients were enrolled following participation in a double-blind trial or one of two open-label trials of adjunctive lacosamide for partial-onset seizures. Dosage adjustments of lacosamide (100-800 mg/day) and/or concomitant antiepileptic drugs were allowed to optimize tolerability and seizure reduction. Of the 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years of lacosamide exposure, respectively. Median lacosamide modal dose was 400mg/day. Common treatment-emergent adverse events (TEAEs) were dizziness (39.7%), headache (20.8%), nausea (17.3%), diplopia (17.0%), fatigue (16.5%), upper respiratory tract infection (16.5%), nasopharyngitis (16.2%), and contusion (15.4%). Dizziness (2.2%) was the only TEAE that led to discontinuation in >2% of patients. Ranges for median percent reductions in seizure frequency were 47-65%, and those for ≥ 50% responder rates were 49-63% for 1-, 3-, and 5-year completer cohorts. Exposure to lacosamide for up to 8 years was generally well tolerated, with a safety profile similar to previous double-blind trials, and efficacy was maintained. Copyright © 2014 Elsevier Inc. All rights reserved.

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: an open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728].

PubMed

Oldham, Nicola S; Wright, Nat M J; Adams, Clive E; Sheard, Laura; Tompkins, Charlotte N E

2004-04-29

Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification 8 has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

Efficacy of metacognitive therapy for prolonged grief disorder: protocol for a randomised controlled trial

PubMed Central

Wenn, Jenine; O'Connor, Moira; Breen, Lauren J; Kane, Robert T; Rees, Clare S

2015-01-01

Introduction Studies of effective psychotherapy for individuals suffering from the effects of prolonged grief disorder (PGD) are scarce. This paper describes the protocol for an evaluation of a metacognitive therapy programme designed specifically for PGD, to reduce the psychological distress and loss of functioning resulting from bereavement. Methods and analysis The proposed trial comprises three phases. Phase 1 consists of a review of the literature and semistructured interviews with key members of the target population to inform the development of a metacognitive therapy programme for Prolonged Grief. Phase 2 involves a randomised controlled trial to implement and evaluate the programme. Male and female adults (N=34) will be randomly assigned to either a wait list or an intervention group. Measures of PGD, anxiety, depression, rumination, metacognitions and quality of life will be taken pretreatment and posttreatment and at the 3-month and 6-month follow-up. The generalised linear mixed model will be used to assess treatment efficacy. Phase 3 will test the social validity of the programme. Discussion This study is the first empirical investigation of the efficacy of a targeted metacognitive treatment programme for PGD. A focus on identifying and changing the metacognitive mechanisms underpinning the development and maintenance of prolonged grief is likely to be beneficial to theory and practice. Ethics Ethics approval was obtained from Curtin University Human Research Ethics Committee (Approval number HR 41/2013.) Trial registration number ACTRN12613001270707. PMID:26646828

Systematic review of efficacy of nutraceuticals to alleviate clinical signs of osteoarthritis.

PubMed

Vandeweerd, J-M; Coisnon, C; Clegg, P; Cambier, C; Pierson, A; Hontoir, F; Saegerman, C; Gustin, P; Buczinski, S

2012-01-01

Various treatments of osteoarthritis (OA) have been described, including use of nutraceuticals. To review systematically the literature about the effects of nutraceuticals on clinical signs of pain or abnormal locomotion in horses, dogs, and cats, and to discuss methodological aspects of trials and systematic reviews. A systematic search of controlled trials evaluating the impact of nutraceuticals on OA in horses, dogs, and cats was performed, using Medline, CAB Abstracts, and Google Scholar. Scientific evidence was evaluated by means of criteria proposed by the Food and Drug Administration (FDA), and a scoring system adapted from both the CONsolidated Standards of Reporting Trials (CONSORT) statement and recommendations for assessing trials by the Center of Evidence Based Medicine of Oxford. Twenty-two papers were selected and reviewed, with 5 studies performed in horses, 16 in dogs, and 1 in cats. The strength of evidence was low for all nutraceuticals except for omega-3 fatty acid in dogs. There were limited numbers of rigorous randomized controlled trials and of participants in clinical trials. The evidence of efficacy of nutraceuticals is poor, with the exception of diets supplemented with omega-3 fatty acids in dogs. Greater access to systematic reviews must be part of the objectives of the veterinary science in the future. Their reporting would be improved by internationally agreed-upon criteria for standards and guidelines. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Tenofovir Alafenamide.

PubMed

Gibson, Amanda K; Shah, Bhavik M; Nambiar, Puja H; Schafer, Jason J

2016-11-01

To review the pharmacology, efficacy, safety, and place in therapy for tenofovir alafenamide (TAF). A search using PubMed was conducted (2004 to May 2016) using the following keywords: tenofovir alafenamide, TAF, and GS-7340. Articles were evaluated for content, and bibliographies were reviewed. Data available exclusively as abstracts from major infectious diseases and HIV conferences were also evaluated for inclusion. Studies included were in vitro investigations; phase I, II, and III clinical trials; and pharmacokinetic and pharmacodynamic evaluations. Similar to tenofovir disoproxil fumarate (TDF), TAF is a prodrug of tenofovir but results in significantly higher intracellular tenofovir concentrations and lower serum levels. As a result, TAF is expected to have efficacy similar to that of TDF while reducing tenofovir-associated nephrotoxicity and bone mineral density losses. Clinical trials evaluating the safety and efficacy of TAF-containing antiretroviral regimens have confirmed these expectations, consistently demonstrating similar virological suppression compared with TDF-containing regimens as well as significant improvements in markers of kidney function and bone health. Three combination products containing TAF were approved by the United States Food and Drug Administration for the management of HIV-1 infection. The first of these was a single tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF which is now a recommended regimen in clinical practice guidelines for initial treatment in antiretroviral-naïve patients. TAF is a novel nucleotide reverse transcriptase inhibitor for the treatment of HIV-1 infection that has efficacy similar to that of TDF and improved safety compared with TDF.

Performance of Crohn's disease Clinical Trial Endpoints based upon Different Cutoffs for Patient Reported Outcomes or Endoscopic Activity: Analysis of EXTEND Data.

PubMed

Feagan, Brian; Sandborn, William J; Rutgeerts, Paul; Levesque, Barrett G; Khanna, Reena; Huang, Bidan; Zhou, Qian; Maa, Jen-Fue; Wallace, Kori; Lacerda, Ana; Thakkar, Roopal B; Robinson, Anne M

2018-04-23

Clinical trial endpoints for Crohn's disease (CD) activity correlate poorly with mucosal inflammation; to assess treatment efficacy, patient-reported outcomes and endoscopic assessments are preferred. This study assessed the impact on treatment efficacy estimations of using different definitions of clinical and endoscopic remission and endoscopic response, and of using site- or central-based endoscopy evaluation. This post hoc analysis of data fromEXTEND (extend the safety and efficacy of adalimumab through endoscopic healing), a placebo (PBO)-controlled, randomized trial of adalimumab (ADA) for mucosal healing, included adults with moderate-to-severe CD. Subsets of patients meeting specified Simplified Endoscopic Score for CD (SES-CD) inclusion criteria, according to site or central reading, and baseline stool frequency (SF) and/or abdominal pain score (AP) thresholds were evaluated. Various endpoint definitions based on the Crohn's Disease Activity Index (CDAI), its SF and AP components, SES-CD, and composite endpoints were compared between treatment groups. Increased stringency of Week 12 clinical endpoints compared to CDAI<150 to SF≤3.0/1.5&AP≤1.0 reduced PBO response rates by ≥12% and increased treatment effects by ≤10%. Amending the SES-CD endpoint from ≤4 to ≤2 reduced the treatment effect from 24% to 8%. Composite endpoints further diminished response rates and effect sizes. Site-based evaluation was associated with lower remission rates versus central reading in the PBO group and, thus, greater ADA-related treatment effects. This analysis is the first to demonstrate that increasing the stringency of clinical and endoscopic endpoint definitions in CD trials, especially lowering SF or SES-CD definitions, reduces the ability to detect treatment-related change in CD activity; focus on endpoints that reflect clinical change is warranted.

Brief Report: Pilot Randomized Controlled Trial of Reciprocal Imitation Training for Teaching Elicited and Spontaneous Imitation to Children with Autism

ERIC Educational Resources Information Center

Ingersoll, Brooke

2010-01-01

Children with autism exhibit significant deficits in imitation skills. Reciprocal Imitation Training (RIT), a naturalistic imitation intervention, was developed to teach young children with autism to imitate during play. This study used a randomized controlled trial to evaluate the efficacy of RIT on elicited and spontaneous imitation skills in 21…

Changing Parent's Mindfulness, Child Management Skills and Relationship Quality with Their Youth: Results from a Randomized Pilot Intervention Trial

ERIC Educational Resources Information Center

Coatsworth, J. Douglas; Duncan, Larissa G.; Greenberg, Mark T.; Nix, Robert L.

2010-01-01

We evaluated the efficacy of a mindful parenting program for changing parents' mindfulness, child management practices, and relationships with their early adolescent youth and tested whether changes in parents' mindfulness mediated changes in other domains. We conducted a pilot randomized trial with 65 families and tested an adapted version of the…

Reducing Sexual Risk Behaviors and Alcohol Use among HIV-Positive Men Who Have Sex with Men: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Velasquez, Mary M.; von Sternberg, Kirk; Johnson, David H.; Green, Charles; Carbonari, Joseph P.; Parsons, Jeffrey T.

2009-01-01

This randomized clinical trial (N = 253) evaluated the efficacy of a theory-based intervention designed to reduce both alcohol use and incidence of unprotected sexual behaviors among HIV-positive men who have sex with men with alcohol use disorders. An integrated, manualized intervention, using both individual counseling and peer group…

Efficacy of the Lexicon Pirate Strategy Therapy for Improving Lexical Learning in School-Age Children: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Motsch, Hans-Joachim; Marks, Dana-Kristin

2015-01-01

Lexicon Pirate was originally developed as a strategy intervention programme to treat lexical disorders of pre-school children. To evaluate the therapy's effectiveness for school-age students, a randomized controlled trial (RCT, N = 157) was conducted. Based on a pre--post-test design, the programme's impacts were compared with a control group…

A Parent-Mediated Intervention that Targets Responsive Parental Behaviors Increases Attachment Behaviors in Children with ASD: Results from a Randomized Clinical Trial

ERIC Educational Resources Information Center

Siller, Michael; Swanson, Meghan; Gerber, Alan; Hutman, Ted; Sigman, Marian

2014-01-01

The current study is a randomized clinical trial evaluating the efficacy of Focused Playtime Intervention (FPI) in a sample of 70 children with Autism Spectrum Disorder. This parent-mediated intervention has previously been shown to significantly increase responsive parental communication (Siller et al. in "J Autism Dev Disord"…

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

ERIC Educational Resources Information Center

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

2015-01-01

Purpose: In this study, we aimed to evaluate the efficacy of sentence-combining (SC) and narrative-based (NAR) intervention approaches to syntax intervention using a randomized-controlled-trial design. Method: Fifty-two Cantonese-speaking, school-age children with language impairment were assigned randomly to either the SC or the NAR treatment…

Randomized Controlled Trial of "Mind Reading" and In Vivo Rehearsal for High-Functioning Children with ASD

ERIC Educational Resources Information Center

Thomeer, Marcus L.; Smith, Rachael A.; Lopata, Christopher; Volker, Martin A.; Lipinski, Alanna M.; Rodgers, Jonathan D.; McDonald, Christin A.; Lee, Gloria K.

2015-01-01

This randomized controlled trial evaluated the efficacy of a computer software (i.e., "Mind Reading") and in vivo rehearsal treatment on the emotion decoding and encoding skills, autism symptoms, and social skills of 43 children, ages 7-12 years with high-functioning autism spectrum disorder (HFASD). Children in treatment (n = 22)…

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

ERIC Educational Resources Information Center

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

2004-01-01

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

High-dose transdermal nicotine replacement for tobacco cessation.

PubMed

Brokowski, Laurie; Chen, Jiahui; Tanner, Sara

2014-04-15

The safety and efficacy of high-dose transdermal nicotine-replacement therapy (NRT) for the treatment of tobacco-use cessation were reviewed. Transdermal nicotine doses of 7, 14, and 21 mg daily are approved by the Food and Drug Administration for use in tobacco cessation. However, studies have suggested that these doses are more adequate for people who smoke fewer than 20 cigarettes per day. A literature search was conducted to identify English-language studies that evaluated the use of transdermal nicotine doses of ≥42 mg daily. A total of 11 articles were identified, representing 10 separate trials. In terms of safety, the majority of the trials had no reports of serious adverse events related to transdermal NRT at doses of ≥42 mg daily. A dose-response relationship with adverse events occurred in most trials. In terms of efficacy, a numerically higher abstinence rate was achieved with high-dose transdermal NRT in all trials but 1. However, none of the studies showed significant differences in final abstinence rates at follow-up. Some reasons why statistical significance was not achieved in these trials may be related to the limitations of these trials, such as their small samples and the lack of a power calculation. A more robust trial is needed to support higher nicotine transdermal doses in tobacco cessation and to help elucidate which patient population would be most suitable for their use. The safety and efficacy of high-dose transdermal NRT for tobacco cessation have not been established in the medical literature.

Exposure Matching for Extrapolation of Efficacy in Pediatric Drug Development

PubMed Central

Mulugeta, Yeruk; Barrett, Jeffrey S.; Nelson, Robert; Eshete, Abel Tilahun; Mushtaq, Alvina; Yao, Lynne; Glasgow, Nicole; Mulberg, Andrew E.; Gonzalez, Daniel; Green, Dionna; Florian, Jeffry; Krudys, Kevin; Seo, Shirley; Kim, Insook; Chilukuri, Dakshina; Burckart, Gilbert J.

2017-01-01

During drug development, matching adult systemic exposures of drugs is a common approach for dose selection in pediatric patients when efficacy is partially or fully extrapolated. This is a systematic review of approaches used for matching adult systemic exposures as the basis for dose selection in pediatric trials submitted to the U.S. Food and Drug Administration (FDA) between 1998 and 2012. The trial design of pediatric pharmacokinetic (PK) studies and the pediatric and adult systemic exposure data were obtained from FDA publicly available databases containing reviews of pediatric trials. Exposure matching approaches that were used as the basis for pediatric dose selection were reviewed. The PK data from the adult and pediatric populations were used to quantify exposure agreement between the two patient populations. The main measures were the pediatric PK studies trial design elements and drug systemic exposures (adult and pediatric). There were 31 products (86 trials) with full or partial extrapolation of efficacy with an available PK assessment. Pediatric exposures had a range of mean Cmax and AUC ratios (pediatric/adult) of 0.63-4.19 and 0.36-3.60 respectively. Seven of the 86 trials (8.1%) had a pre-defined acceptance boundary used to match adult exposures. The key PK parameter was consistently predefined for antiviral and anti-infective products. Approaches to match exposure in children and adults varied across products. A consistent approach for systemic exposure matching and evaluating pediatric PK studies is needed to guide future pediatric trials. PMID:27040726

The effects of self-efficacy enhancing program on foot self-care behaviour of older adults with diabetes: A randomised controlled trial in elderly care facility, Peninsular Malaysia

PubMed Central

Abdul Rahman, Hejar; Minhat, Halimatus Sakdiah; Shariff-Ghazali, Sazlina; Azman Ong, Mohd Hanafi

2018-01-01

Background Self-care behaviour is essential in preventing diabetes foot problems. This study aimed to evaluate the effectiveness of health education programs based on the self-efficacy theory on foot self-care behaviour for older adults with diabetes. Methods A randomised controlled trial was conducted for 12 weeks among older adults with diabetes in elderly care facility in Peninsular Malaysia. Six elderly care facility were randomly allocated by an independent person into two groups (intervention and control). The intervention group (three elderly care facility) received a health education program on foot self-care behaviour while the control group (three elderly care facility) received standard care. Participants were assessed at baseline, and at week-4 and week-12 follow-ups. The primary outcome was foot-self-care behaviour. Foot care self-efficacy (efficacy expectation), foot care outcome expectation, knowledge of foot care and quality of life were the secondary outcomes. Data were analysed with Mixed Design Analysis of Variance using the Statistical Package for the Social Sciences version 22.0. Results 184 respondents were recruited but only 76 met the selection criteria and were included in the analysis. Foot self-care behaviour, foot care self-efficacy (efficacy expectation), foot care outcome expectation and knowledge of foot care improved in the intervention group compared to the control group (p < 0.05). However, some of these improvements did not significantly differ compared to the control group for QoL physical symptoms and QoL psychosocial functioning (p > 0.05). Conclusion The self-efficacy enhancing program improved foot self-care behaviour with respect to the delivered program. It is expected that in the future, the self-efficacy theory can be incorporated into diabetes education to enhance foot self-care behaviour for elderly with diabetes living in other institutional care facilities. Trial registration Australian New Zealand Clinical Trial Registry ACTRN12616000210471 PMID:29534070

Using the World Wide Web in health-related intervention research. A review of controlled trials.

PubMed

Kirsch, Sallie E; Lewis, Frances M

2004-01-01

A review of published controlled trials was conducted to evaluate components, utility, and efficacy of Web-based healthcare interventions. Nine studies met the established review criteria. Knowledge gains were the most commonly reported significant changes; rarely were there measures or significant changes on behavioral outcomes. Studies varied in format of personal contact with participants, in the structure or sequence of intervention content, and in design features. Dosage was inconsistently measured and process evaluation was relatively absent. Despite limitations, several studies reported significant effects. Based on best evidence-to-date, elements of technologically mediated interventions important to future research are summarized. Taken together, research suggests that Web-based interventions may be an efficacious delivery system, especially for those with chronic conditions amenable to self-management and to those with various limitations to accessing healthcare.

Safety and efficacy of injectable and oral maropitant, a selective neurokinin 1 receptor antagonist, in a randomized clinical trial for treatment of vomiting in dogs.

PubMed

Ramsey, D S; Kincaid, K; Watkins, J A; Boucher, J F; Conder, G A; Eagleson, J S; Clemence, R G

2008-12-01

Maropitant (Cerenia), a selective neurokinin(1) receptor antagonist, was evaluated for safety and efficacy in treatment and prevention of acute vomiting due to various etiologies in dogs in a randomized clinical trial. Two-hundred seventy-eight dogs were enrolled from 29 veterinary hospitals. Two-hundred fifty-two were evaluable for efficacy, while 275 were evaluable for safety. A randomized block design was utilized (three maropitant- and one placebo-treated dog per block). Initial treatment was maropitant at 1 mg/kg body weight (0.45 mg/lb) or an equivalent volume of saline (placebo) administered subcutaneously. On the subsequent 1 to 4 days, maropitant or placebo (dependent on allocation) was administered subcutaneously or orally at approximate 24-h intervals as needed. Oral doses were administered as maropitant tablets using unit dosing to deliver a minimum dose of 2 mg/kg body weight (0.9 mg/lb) or equivalent numbers of similar placebo tablets. Dogs and housing were observed twice daily for evidence of vomiting. Emesis was significantly (P

Efficacy of Acupuncture for Bell's Palsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Li, Pingping; Qiu, Tangmeng; Qin, Chao

2015-01-01

Acupuncture has emerged as an alternative therapy for Bell's palsy in both adults and children. However, the use of acupuncture is controversial. We conducted a systematic review and meta-analysis to assess the efficacy of acupuncture for Bell's palsy. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, irrespective of any language restrictions. Randomized controlled trials comparing acupuncture with other therapies for Bell's palsy in adults or children were included. Fourteen randomized controlled trials involving 1541 individuals were included in this meta-analysis. Significant association was observed in acupuncture with a higher effective response rate for Bell's palsy (relative risk, 1.14; 95% confidence interval, 1.04-1.25; P = 0.005) but there was a heterogeneity among the studies (I2 = 87%). An assessment of the included studies revealed a high risk of bias in methodological quality. An evaluation of the incidence of complications was not available, owing to incomplete data. Acupuncture seems to be an effective therapy for Bell's palsy, but there was insufficient evidence to support the efficacy and safety of acupuncture. However, the results should be interpreted cautiously, because of the poor quality and heterogeneity of the included studies.

Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naïve to enzyme replacement therapy or previously treated with imiglucerase.

PubMed

Smith, Laurie; Rhead, William; Charrow, Joel; Shankar, Suma P; Bavdekar, Ashish; Longo, Nicola; Mardach, Rebecca; Harmatz, Paul; Hangartner, Thomas; Lee, Hak-Myung; Crombez, Eric; Pastores, Gregory M

2016-02-01

Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Identifier NCT00635427). Safety and efficacy were evaluated in pediatric patients receiving velaglucerase alfa 30-60U/kg by intravenous infusion every other week. In addition to key hematological and visceral efficacy assessments, exploratory assessments conducted specifically in pediatric patients included evaluation of height, bone age, bone marrow burden, and Tanner stage of puberty. The study included 24 pediatric patients. Fifteen patients were naïve to ERT on entry into the preceding trials TKT032 (12-month trial) or HGT-GCB-039 (9-month trial): in the preceding trials, ten of these 15 patients received velaglucerase alfa and five patients received imiglucerase ERT. Nine patients in the study were previously treated with imiglucerase for >30months and were switched to velaglucerase alfa in the preceding trial TKT034 (12-month trial). Cumulative ERT exposure in the clinical studies ranged from 2.0 to 5.8years. Three serious adverse events, including a fatal convulsion, were reported; none were deemed related to velaglucerase alfa. One patient tested positive for anti-velaglucerase alfa antibodies. An efficacy assessment at 24months showed that velaglucerase alfa had positive effects on primary hematological and visceral parameters in treatment-naïve patients, which were maintained with longer-term treatment. Disease parameters were stable in patients switched from long-term imiglucerase ERT. Exploratory results may suggest benefits of early treatment to enable normal growth in pediatric patients. The safety profile and clinical response seen in pediatric patients are consistent with results reported in adults. Copyright © 2016 Shire Development LLC. Published by Elsevier Inc. All rights reserved.

Meta-analysis of five photodisinfection clinical trials for periodontitis

NASA Astrophysics Data System (ADS)

Andersen, Roger C.; Loebel, Nicolas G.; Andersen, Dane M.

2009-06-01

Photodynamic therapy(PDT) has been demonstrated to effectively kill human periopathogens in vitro. To evaluate the efficacy of PDT in vivo a series of clinical trials was carried out in multiple centers and populations. Clinical parameters including clinical attachment level, pocket probing depth and bleeding on probing were all evaluated. All groups received the standard of care, scaling and root planing, and the treatment group additionally received a single treatment of PDT. Of the total 309 patients and over 40,000 pockets treated in these 5 trials it was determined that photodynamic therapy provided a statistically significant improvement in clinical parameters over scaling and root planing alone.

Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis.

PubMed

Moser, Wendelin; Schindler, Christian; Keiser, Jennifer

2017-09-25

Objective  To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates. Design  Systematic review and network meta-analysis. Data Sources  PubMed, ISI Web of Science, Embase, ScienceDirect, the Cochrane Central Register of Clinical Trials, and the World Health Organization library database from 1960 until 31 December 2016. Study selection  Randomised controlled trials evaluating the efficacy of a single dose regimen of albendazole, mebendazole, levamisole, and pyrantel pamoate against Ascaris lumbricoides , hookworm ( Necator americanus and Ancylostoma duodenale ) and Trichuris trichiura. The primary outcomes included cure rates analysed by network meta-analysis with mixed logistic regression models and egg reduction rates with mixed linear models. Results  55 and 46 randomised controlled trials were included in the analysis of cure rates and egg reduction rates, respectively. All drugs were highly efficacious against A lumbricoides Albendazole showed the highest efficacy against hookworm infections with a cure rate of 79.5% (95% confidence interval 71.5% to 85.6%) and an egg reduction rate of 89.6% (81.9% to 97.3%). All drugs had low efficacy against T trichiura , with mebendazole showing the highest cure rate of 42.1% (25.9% to 60.2%) and egg reduction rate of 66.0% (54.6% to 77.3%). Estimates for the years 1995 and 2015 showed significant reductions in efficacy of albendazole against T trichiura : by 2015 the egg reduction rates fell from 72.6% (53.7% to 91.5%) to 43.4% (23.5% to 63.3%; P=0.049) and the cure rates fell from 38.6% (26.2% to 52.7%) to 16.4 (7.7% to 31.3%; P=0.027). Conclusions  All four currently recommended drugs show limitations in their efficacy profile. While only albendazole showed good efficacy against hookworm infection, all drugs had low efficacy against T trichiura The decrease in efficacy of albendazole against T trichiura over the past two decades is of concern. The findings indicate the need for strengthening efforts to develop new drug treatments, with a particular focus on drugs against T trichiura . Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Introduction: the goals of antimicrobial therapy.

PubMed

Song, Jae-Hoon

2003-03-01

Antimicrobial agents are generally evaluated in preclinical studies assessing in vitro activity, animal models demonstrating in vivo bacteriologic efficacy, and clinical trials primarily investigating safety and clinical efficacy. However, large sample sizes are required to detect any differences in outcomes between antimicrobials in clinical trials, and, generally, studies are powered to show only clinical equivalence. In addition, diagnosis is often based on clinical symptoms, rather than microbiological evidence of bacterial infection, and the patients most likely to have resistant pathogens are often excluded. Clinical efficacy can be achieved in some bacterial infections in which antimicrobials are suboptimal or even not prescribed. However, bacterial eradication maximizes clinical efficacy and may also reduce the development and spread of resistant organisms. The goal of antimicrobial therapy is, therefore, to eradicate bacteria at the site of infection. Bacterial eradication is not usually assessed as a primary endpoint within the limits of currently recommended clinical trial design. However, pharmacokinetic (PK) (serum concentration profiles, penetration to site of infection) and pharmacodynamic (PD) (susceptibility, concentration- versus time-dependent killing, post-antimicrobial effects) criteria can be used to predict bacteriologic efficacy. PK/PD predictions should be confirmed during all phases of antimicrobial development and throughout clinical use in response to changing patterns of resistance. A clear rationale for dose recommendations can be determined preclinically based on PK/PD parameters, and correlated with efficacy, safety and resistance endpoints in clinical trials. The duration of treatment and dose should be the shortest that will reliably eradicate the pathogen(s), and that is safe and well tolerated. Currently available agents vary significantly in their ability to achieve PK/PD parameters necessary for bacteriologic eradication. Recommendations for appropriate antimicrobial therapy should be based on PK/PD parameters, with the aim of achieving the maximum potential for eradication of both existing and emerging resistant pathogens.

Evaluating the efficacy of an integrated motivational interviewing and multi-modal exercise intervention for youth with major depression: Healthy Body, Healthy Mind randomised controlled trial protocol.

PubMed

Nasstasia, Yasmina; Baker, Amanda L; Halpin, Sean A; Hides, Leanne; Lewin, Terry J; Kelly, Brian J; Callister, Robin

2018-03-01

Recent meta-analytic reviews suggest exercise can reduce depression severity among adults with major depressive disorder (MDD); however, efficacy studies with depressed youth are limited. Few studies have investigated the efficacy of multi-modal exercise interventions in this population, addressed treatment engagement, or explored the differential effects of exercise on depressive symptom profiles. This paper describes the study protocol and recruitment pattern for an assessor blinded, two-arm randomised controlled trial investigating the efficacy of an integrated motivational interviewing (MI) and multi-modal exercise intervention in youth diagnosed with MDD. Associations between depressive symptom profiles (cognitive, somatic and affective) and psychological, physiological (fitness), and biological (blood biomarker) outcomes will also be examined. Participants aged 15-25 years with current MDD were recruited. Eligible participants were randomised and stratified according to gender and depression severity to either an immediate or delayed (control) group. The immediate group received a brief MI intervention followed by a 12-week small group exercise intervention (3 times per week for 1 h), all delivered by personal trainers. The delayed control group received the same intervention 12-weeks later. Both groups were reassessed at mid-treatment or mid-control, post-treatment or post-control, and follow-up (12 weeks post-treatment). 68 participants were recruited and randomly allocated to an intervention group. This trial will increase our understanding of the efficacy of multi-modal exercise interventions for depression and the specific effects of exercise on depressive symptom profiles. It also offers a novel contribution by addressing treatment engagement in exercise efficacy trials in youth with MDD.

[Efficacy evaluation of lafutidine for mild reflux esophagitis in Japanese patients].

PubMed

Ohara, Shuichi; Haruma, Ken; Kinoshita, Yoshikazu; Kusano, Motoyasu

2010-04-01

To evaluate the efficacy of lafutidine (20mg) , famotidine (40mg) and placebo in patients with mild reflux esophagitis (Grades A and B according to the Los Angeles classification) , a double-blind, multicenter, randomized clinical trial was performed for the first time in Japanese patients. In addition to each physician's evaluation, efficacy was evaluated by judging panels using images submitted by each physician. The healing rate after 8 weeks for lafutidine, famotidine and placebo were 67.7%, 56.6% and 41.2%, respectively. Lafutidine was significantly more effective than placebo (p=0.002, according to the judging panels) . Based on the evaluation of endoscopic images by the judging panels, 91 (27.1%) of 336 images submitted by each physician were judged to not be mucosal breaks. Judging panels are considered one of the ways to resolve the problem of the need to unify the criteria.

Designing trials for pressure ulcer risk assessment research: methodological challenges.

PubMed

Balzer, K; Köpke, S; Lühmann, D; Haastert, B; Kottner, J; Meyer, G

2013-08-01

For decades various pressure ulcer risk assessment scales (PURAS) have been developed and implemented into nursing practice despite uncertainty whether use of these tools helps to prevent pressure ulcers. According to current methodological standards, randomised controlled trials (RCTs) are required to conclusively determine the clinical efficacy and safety of this risk assessment strategy. In these trials, PURAS-aided risk assessment has to be compared to nurses' clinical judgment alone in terms of its impact on pressure ulcer incidence and adverse outcomes. However, RCTs evaluating diagnostic procedures are prone to specific risks of bias and threats to the statistical power which may challenge their validity and feasibility. This discussion paper critically reflects on the rigour and feasibility of experimental research needed to substantiate the clinical efficacy of PURAS-aided risk assessment. Based on reflections of the methodological literature, a critical appraisal of available trials on this subject and an analysis of a protocol developed for a methodologically robust cluster-RCT, this paper arrives at the following conclusions: First, available trials do not provide reliable estimates of the impact of PURAS-aided risk assessment on pressure ulcer incidence compared to nurses' clinical judgement alone due to serious risks of bias and insufficient sample size. Second, it seems infeasible to assess this impact by means of rigorous experimental studies since sample size would become extremely high if likely threats to validity and power are properly taken into account. Third, means of evidence linkages seem to currently be the most promising approaches for evaluating the clinical efficacy and safety of PURAS-aided risk assessment. With this kind of secondary research, the downstream effect of use of PURAS on pressure ulcer incidence could be modelled by combining best available evidence for single parts of this pathway. However, to yield reliable modelling results, more robust experimental research evaluating specific parts of the pressure ulcer risk assessment-prevention pathway is needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Field efficacy and safety of an oral formulation of the novel combination anthelmintic, derquantel-abamectin, in sheep in New Zealand

PubMed Central

Little, PR; Hodge, A; Watson, TG; Seed, JA; Maeder, SJ

2011-01-01

AIM: To evaluate the efficacy and safety of the novel anthelmintic combination, derquantel-abamectin, against gastrointestinal nematode populations in sheep, under field-use conditions. METHODS: Controlled faecal egg count reduction tests (FECRT) were conducted in New Zealand in 14 trials, covering a range of geographic locations, farming enterprises, breeds, nematode populations, and anthelmintic-resistance profiles. Enrolled animals were naturally infected with mixed populations of gastrointestinal nematodes. All trials included a group treated with derquantel-abamectin, and a negative control group. Nine trials included additional groups each treated with a single- or dual-active oral reference anthelmintic, selected from albendazole, levamisole, albendazole-levamisole, ivermectin, abamectin and moxidectin. A total of 838 animals were enrolled across all trials, and were randomly allocated to treatment groups within blocks defined by faecal nematode egg counts (FEC) pre-treatment. On Day 0 derquantel-abamectin was administered orally at 1 ml/5 kg bodyweight (2 mg/kg derquantel, 0.2 mg/ kg abamectin), and each reference anthelmintic was given at the recommended label dose. Faecal samples were collected on Day 14 (± 1 day), to determine the percentage reduction in mean FEC for each anthelmintic tested. Larval differentiation was also performed post-treatment, to estimate efficacy at the genus level. Animals were weighed on or before Day 0, and on Day 14 (± 1 day) in 13 trials. RESULTS: The efficacy of derquantel-abamectin against mixed strongyle populations was ≥99.2%, based on the percentage reduction in geometric mean FEC. Nematodirus sp. was present in six trials at a level sufficient for efficacy calculations to be conducted; in all cases, the efficacy of derquantel-abamectin was 100%. In those trials where the efficacy of at least one reference anthelmintic was <95% against strongyles and/or Nematodirus sp., derquantel-abamectin was 100% effective. In five trials, the mean gain in bodyweight was significantly greater in the derquantel-abamectin group than the negative controls. CONCLUSIONS AND CLINICAL RELEVANCE: When administered orally at 1 ml/5 kg bodyweight, derquantel-abamectin is highly effective for the treatment of gastrointestinal nematodes in sheep, including populations of strongyles and Nematodirus sp. with resistance to one or more single- or dual-active anthelmintics. Derquantel-abamectin presents sheep producers with a unique opportunity to introduce a new class of anthelmintic to their nematode control programmes, with the added benefits offered by a combination anthelmintic. PMID:20514085

Evaluation of insecticides on cotton fleahopper and beneficial arthropod populations

USDA-ARS?s Scientific Manuscript database

An experiment was initiated in 2009 concurrently with a cotton fleahopper insecticide efficacy trial to determine which products were the most and least detrimental to arthropod natural enemies. Insecticides evaluated included Bidrin 8E, Bidrin XP, Centric 40WG, Discipline 2EC, Intruder 70WP, Orthe...

Texting Parents: Evaluation Report and Executive Summary

ERIC Educational Resources Information Center

Miller, Sarah; Davison, Jenny; Yohanis, Jamie; Sloan, Seaneen; Gildea, Aideen; Thurston, Allen

2017-01-01

This report presents the findings from an efficacy trial and process evaluation of the Parent Engagement Programme (PEP). The PEP was a school-level intervention designed to improve pupil outcomes by engaging parents in their children's learning. The programme was developed collaboratively by research teams from the University of Bristol and…

Validity and Reliability of a Parental Self-Efficacy Instrument in the Healthy School Start Prevention Trial of Childhood Obesity

ERIC Educational Resources Information Center

Bohman, Benjamin; Nyberg, Gisela; Sundblom, Elinor; Schäfer Elinder, Liselotte

2014-01-01

Introduction: Measures of parental self-efficacy (PSE) for healthy dietary or physical activity (PA) behaviors in children have been used in several studies; however, further psychometric validation of PSE for these behaviors is needed. The purpose of the present study was to evaluate the psychometric properties of a new PSE instrument. Methods:…

Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials.

PubMed

Lodise, Thomas P; Redell, Mark; Armstrong, Shannon O; Sulham, Katherine A; Corey, G Ralph

2017-01-01

The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials. SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) oritavancin versus 7-10 days of twice-daily IV vancomycin for the treatment of ABSSSI. Protocols were amended to allow enrolled patients to complete their entire course of antimicrobial therapy in an outpatient setting. The primary efficacy outcome was a composite endpoint (cessation of spread or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic at early clinical evaluation [ECE]) (48 to 72 hours). Key secondary endpoints included investigator-assessed clinical cure 7 to 14 days after end of treatment (posttherapy evaluation [PTE]) and 20% or greater reduction in lesion area at ECE. Safety was assessed until day 60. Seven hundred ninety-two patients (oritavancin, 392; vancomycin, 400) received entire course of treatment in the outpatient setting. Efficacy response rates at ECE and PTE were similar (primary composite endpoint at ECE: 80.4% vs 77.5% for oritavancin and vancomycin, respectively) as was incidence of adverse events. Five patients (1.3%) who received oritavancin and 9 (2.3%) vancomycin patients were subsequently admitted to a hospital. Oritavancin provides a single-dose alternative to multidose vancomycin for treatment of ABSSSI in the outpatient setting. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Evaluation of the efficacy of a polyherbal mouthwash containing Zingiber officinale, Rosmarinus officinalis and Calendula officinalis extracts in patients with gingivitis: A randomized double-blind placebo-controlled trial.

PubMed

Mahyari, Saman; Mahyari, Behnam; Emami, Seyed Ahmad; Malaekeh-Nikouei, Bizhan; Jahanbakhsh, Seyedeh Pardis; Sahebkar, Amirhossein; Mohammadpour, Amir Hooshang

2016-02-01

Gingivitis is a highly prevalent periodontal disease resulting from microbial infection and subsequent inflammation. The efficacy of herbal preparations in subjects with gingivitis has been reported in some previous studies. To investigate the efficacy of a polyherbal mouthwash containing hydroalcoholic extracts of Zingiber officinale, Rosmarinus officinalis and Calendula officinalis (5% v/w) compared with chlorhexidine and placebo mouthwashes in subjects with gingivitis. Sixty patients participated in this randomized double-blind placebo-controlled trial and were randomly assigned to the polyherbal mouthwash (n = 20), chlorhexidine mouthwash (n = 20) or placebo mouthwash (n = 20). Participants were instructed to use the mouthwash twice a day (after breakfast and dinner) for 30 s for a period of two weeks. Gingival and plaque indices were assessed using MGI, GBI and MQH scales at baseline, day 7 and day 14 of the trial. There were significant improvements in all assessed efficacy measures i.e. MGI, GBI and MQH scores from baseline to the end of trial in both polyherbal and chlorhexidine mouthwash groups; however, the scores remained statistically unchanged in the placebo group. MGI, BGI and MQH scores in the treatment groups were significantly lower compared with those of the control group at both day 7 and day 14 of the trial. However, there was no significant difference between the polyherbal and chlorhexidine groups, neither at day 7 nor day 14 of the trial. Polyherbal mouthwash was safe and there was neither report of adverse reactions, nor any drop-out during the course of study. Polyherbal mouthwash containing hydroalcoholic extracts of Z. officinale, R. officinalis and C. officinalis (5%) was effective in the treatment of gingivitis and its efficacy was comparable to that of chlorhexidine mouthwash. Copyright © 2015 Elsevier Ltd. All rights reserved.

Blood pressure control with amlodipine add-on therapy in patients with hypertension and diabetes: results of the Amlodipine Diabetic Hypertension Efficacy Response Evaluation Trial.

PubMed

Kloner, Robert A; Neutel, Joel; Roth, Eli M; Weiss, Robert; Weinberger, Myron H; Thakker, Kamlesh M; Schwartz, Brian; Shi, Harry; Gregg, Anne-Marie

2008-11-01

Attainment of blood pressure (BP) goals in patients with diabetes is critical both to reduce the risk of cardiovascular events and to delay the progression of renal disease. While therapeutic guidelines advise initial therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, monotherapy with these agents may not be sufficient to attain target BP. The ADHT (Amlodipine Diabetic Hypertension Efficacy Response Evaluation Trial) evaluated the efficacy and safety of adding amlodipine to the treatment regimen of patients with hypertension and diabetes who were already receiving either quinapril or losartan as monotherapy. ADHT was a double-blind, double-dummy, 22-week trial conducted in the US. After a washout period of 7-13 days, patients (aged 30-75 y) with hypertension and diabetes were randomized to receive quinapril 20 mg/day plus placebo or losartan 50 mg/day plus placebo for 4 weeks, titrated to 40 mg or 100 mg (if required), respectively, for an additional 4 weeks to achieve their BP goals (<130/80 mm Hg). At week 8, either amlodipine 5 mg/day or placebo was added for an additional 12 weeks, with titration to 10 mg at week 14 if the BP goal was not achieved. Efficacy of add-on therapy was evaluated in 411 patients (amlodipine 211, placebo 200). BP goal was reached by 27.5% of patients when amlodipine was added to quinapril or losartan monotherapy, compared with 12.5% when placebo was added (OR 2.73; 95% CI 1.61 to 4.64; p < 0.001). When added to quinapril or losartan monotherapy, amlodipine reduced BP by 8.1/5.4 mm Hg, compared with a 1.6/0.7 mm Hg decrease with add-on placebo (p < 0.001). Amlodipine, quinapril, and losartan were well tolerated. Amlodipine is safe and effective when added to quinapril or losartan monotherapy to help lower BP toward therapeutic targets in patients with hypertension and diabetes.

A Grading System To Evaluate Objectively the Strength of Pre-Clinical Data of Acute Neuroprotective Therapies for Clinical Translation in Spinal Cord Injury

PubMed Central

Okon, Elena B.; Tsai, Eve; Beattie, Michael S.; Bresnahan, Jacqueline C.; Magnuson, David K.; Reier, Paul J.; McTigue, Dana M.; Popovich, Phillip G.; Blight, Andrew R.; Oudega, Martin; Guest, James D.; Weaver, Lynne C.; Fehlings, Michael G.; Tetzlaff, Wolfram

2011-01-01

Abstract The past three decades have seen an explosion of research interest in spinal cord injury (SCI) and the development of hundreds of potential therapies that have demonstrated some promise in pre-clinical experimental animal models. A growing number of these treatments are seeking to be translated into human clinical trials. Conducting such a clinical trial, however, is extremely costly, not only for the time and money required to execute it, but also for the limited resources that will then no longer be available to evaluate other promising therapies. The decision about what therapies have sufficient pre-clinical evidence of efficacy to justify testing in humans is therefore of utmost importance. Here, we have developed a scoring system for objectively grading the body of pre-clinical literature on neuroprotective treatments for acute SCI. The components of the system include an evaluation of a number of factors that are thought to be important in considering the “robustness” of a therapy's efficacy, including the animal species and injury models that have been used to test it, the time window of efficacy, the types of functional improvements effected by it, and whether efficacy has been independently replicated. The selection of these factors was based on the results of a questionnaire that was performed within the SCI research community. A modified Delphi consensus-building exercise was then conducted with experts in pre-clinical SCI research to refine the criteria and decide upon how to score them. Finally, the grading system was applied to a series of potential neuroprotective treatments for acute SCI. This represents a systematic approach to developing an objective method of evaluating the extent to which the pre-clinical literature supports the translation of a particular experimental treatment into human trials. PMID:20507235

Economic evaluations of trastuzumab in HER2-positive metastatic breast cancer: a systematic review and critique.

PubMed

Parkinson, Bonny; Pearson, Sallie-Anne; Viney, Rosalie

2014-01-01

Published economic evaluations of trastuzumab for the treatment of HER2-positive metastatic breast cancer have arrived at different conclusions regarding the cost-effectiveness of trastuzumab, despite comparative efficacy being demonstrated by a small set of randomised controlled trials (RCTs). This article aims to provide insight into the quality of the evaluations and explore the possible drivers of the conflicting conclusions. A systematic literature review was conducted to identify all published economic evaluations that compared the incremental costs and outcomes of trastuzumab versus a comparator. Fifteen economic evaluations were identified. In the evaluations that estimated efficacy using an RCT, the key drivers of the conclusions regarding cost-effectiveness were: the approach used to estimate overall survival in the control group given crossover to trastuzumab following progression in the trials; the inclusion of treatment beyond progression; inclusion of wastage due to unused vial portions, adverse events, and the cost of HER2 testing. Four evaluations used non-randomised approaches to estimate efficacy, thus introducing the potential for confounding. As a result these evaluations reported relatively optimistic estimates of comparative effectiveness. Finally the evaluations used different thresholds to determine whether treatment with trastuzumab was cost-effective. There were numerous drivers of the different conclusions regarding the cost-effectiveness of trastuzumab, many of which are due to judgements made by the authors when translating data from RCTs. Many of the potential drivers were not identified by the published systematic reviews of economic evaluations and perhaps more remain unidentified because of inconsistent and limited reporting.

Efficacy of Curcuma for Treatment of Osteoarthritis

PubMed Central

Perkins, Kimberly; Sahy, William; Beckett, Robert D.

2016-01-01

The objective of this review is to identify, summarize, and evaluate clinical trials to determine the efficacy of curcuma in the treatment of osteoarthritis. A literature search for interventional studies assessing efficacy of curcuma was performed, resulting in 8 clinical trials. Studies have investigated the effect of curcuma on pain, stiffness, and functionality in patients with knee osteoarthritis. Curcuma-containing products consistently demonstrated statistically significant improvement in osteoarthritis-related endpoints compared with placebo, with one exception. When compared with active control, curcuma-containing products were similar to nonsteroidal anti-inflammatory drugs, and potentially to glucosamine. While statistical significant differences in outcomes were reported in a majority of studies, the small magnitude of effect and presence of major study limitations hinder application of these results. Further rigorous studies are needed prior to recommending curcuma as an effective alternative therapy for knee osteoarthritis. PMID:26976085

Executive summary and recommendations from the WHO/UNAIDS/IAVI expert group consultation on 'Phase IIB-TOC trials as a novel strategy for evaluation of preventive HIV vaccines', 31 January-2 February 2006, IAVI, New York, USA.

PubMed

2007-02-19

This report summarizes the discussions and recommendations from a consultation held in New York City, USA (31 January-2 February 2006) organized by the joint World Health Organization-United Nations Programme on HIV/AIDS HIV Vaccine Initiative and the International AIDS Vaccine Initiative. The consultation discussed issues related to the design and implementation of phase IIB 'test of concept' trials (phase IIB-TOC), also referred to as 'proof of concept' trials, in evaluating candidate HIV vaccines and their implications for future approval and licensure. The results of a single phase IIB-TOC trial would not be expected to provide sufficient evidence of safety or efficacy required for licensure. In many instances, phase IIB-TOC trials may be undertaken relatively early in development, before manufacturing processes and capacity are developed sufficiently to distribute the vaccine on a large scale. However, experts at this meeting considered the pressure that could arise, particularly in regions hardest hit by AIDS, if a phase IIB-TOC trial showed high levels of efficacy. The group largely agreed that full-scale phase III trials would still be necessary to demonstrate that the vaccine candidate was safe and effective, but emphasized that governments and organizations conducting trials should consider these issues in advance. The recommendations from this meeting should be helpful for all organizations involved in HIV vaccine trials, in particular for the national regulatory authorities in assessing the utility of phase IIB-TOC trials in the overall HIV vaccine research and development process.

Efficacy and safety of a biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCEL2) in treating de novo coronary artery disease: A pooled analysis of the CREDIT II and CREDIT III trials.

PubMed

Wang, Geng; Wang, Heyang; Xu, Bo; Yang, Yuejin; Yang, Zhiming; Li, Hui; Zhang, Zheng; Wang, Haichang; Yang, Lixia; Han, Yaling

2017-03-01

The safety and efficacy of the second-generation biodegradable polymer Cobalt-Chromium sirolimus-eluting stent (EXCEL2) in daily clinical practice remains unknown. Additionally, to meet the China Food and Drug Administration requirements, we conducted an objective performance criterion study from the CREDIT II and CREDIT III trials. CREDIT II was a randomized trial comparing the EXCEL2 versus EXCEL stent in patients with up to 2 de novo coronary lesions. CREDIT III was a prospective, single-arm study evaluating the efficacy and safety of EXCEL2 in broad types of de novo coronary artery lesions. This pooled analysis included patients in the CREDIT III and EXCEL2 arm of the CREDIT II trial. The primary outcome was 12-month target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinical indicated target lesion revascularization (CI-TLR). The patient-oriented composite endpoint (PoCE) of all-cause death, all MI, or any revascularization was also analyzed. A total of 833 patients were included, consisting of 625 in the CREDIT III trial and 208 in the EXCEL2 arm of the CREDIT II trial. Twelve-month TLF occurred in 6.1% patients, cardiac death in 0.4%, TV-MI in 5%, and CI-TLR in 1.1%. Additionally, 64 (7.7%) PoCE and 3 probable late stent thromboses (0.4%) were recorded. EXCEL2 stent met the objective performance criterion on efficacy and safety with a low level of 12-month TLF as well as stent thrombosis when treating patients with de novo coronary lesions. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials

PubMed Central

de Sola, Susana; de la Torre, Rafael; Sánchez-Benavides, Gonzalo; Benejam, Bessy; Cuenca-Royo, Aida; del Hoyo, Laura; Rodríguez, Joan; Catuara-Solarz, Silvina; Sanchez-Gutierrez, Judit; Dueñas-Espin, Ivan; Hernandez, Gimena; Peña-Casanova, Jordi; Langohr, Klaus; Videla, Sebastia; Blehaut, Henry; Farre, Magi; Dierssen, Mara; Cuenca-Royo, Aida

2015-01-01

The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome (DS) has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining normalization of DS. PMID:26089807

Generic versus brand-name drugs used in cardiovascular diseases.

PubMed

Manzoli, Lamberto; Flacco, Maria Elena; Boccia, Stefania; D'Andrea, Elvira; Panic, Nikola; Marzuillo, Carolina; Siliquini, Roberta; Ricciardi, Walter; Villari, Paolo; Ioannidis, John P A

2016-04-01

This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider use.

Interventions to Promote Colorectal Cancer Screening: An Integrative Review

PubMed Central

Rawl, Susan M.; Menon, Usha; Burness, Allison; Breslau, Erica S.

2012-01-01

Behavior change interventions to promote colorectal cancer (CRC) screening have targeted people in community and primary care settings, health care providers, and health systems. Randomized controlled trials provide the strongest evidence of intervention efficacy. The purpose of this integrative review was to evaluate trials of CRC screening interventions published between 1997 and 2007 and to identify knowledge gaps and future directions for research. Thirty-three randomized trials that met inclusion criteria were evaluated using a modified version of the TREND criteria. Significant intervention effects were reported in six out of ten trials focused on increasing fecal occult blood testing, four of seven trials focused on sigmoidoscopy or colonoscopy completion, and nine of 16 focused on completion of any screening test. Several effective interventions to promote CRC screening were identified. Future trials need to use theory to guide interventions, examine moderators and mediators, consistently report results, and use comparable outcome measures. PMID:22261002

[Kagocel in the therapy of influenza and acute respiratory viral infections: Data analysis and systematization from the results of preclinical and clinical trials].

PubMed

Sologub, T V; Tsvetkov, V V

The article provides the summarized data of clinical trials evaluating the efficacy and safety of kagocel used to prevent and treat influenza and acute respiratory viral infections of different etiologies. The results of numerous preclinical and clinical trials suggest that the kagocel substance is highly safe and that it is appropriate to use the drug for the treatment and prevention of influenza and acute respiratory viral infections of another etiology.

Evaluation of Bt Corn with Pyramided Genes on Efficacy and Insect Resistance Management for the Asian Corn Borer in China.

PubMed

Jiang, Fan; Zhang, Tiantao; Bai, Shuxiong; Wang, Zhenying; He, Kanglai

2016-01-01

A Bt corn hybrid (AcIe) with two Bt genes (cry1Ie and cry1Ac) was derived by breeding stack from line expressing Cry1Ie and a line expressing Cry1Ac. Efficacy of this pyramided Bt corn hybrid against the Asian corn borer (ACB), Ostrinia furnacalis, was evaluated. We conducted laboratory bioassays using susceptible and resistant ACB strains fed on artificial diet or fresh plant tissues. We also conducted field trials with artificial infestations of ACB neonates at the V6 and silk stages. The toxin-diet bioassay data indicated that mixtures of Cry1Ac and Cry1Ie proteins had synergistic insecticidal efficacy. The plant tissue bioassay data indicated that Bt corn hybrids expressing either a single toxin (Cry1Ac or Cry1Ie) or two toxins had high efficacy against susceptible ACB. Damage ratings in the field trials indicated that the Bt corn hybrids could effectively protect against 1st and the 2nd generation ACB in China. The hybrid line with two Bt genes showed a higher efficacy against ACB larvae resistant to Cry1Ac or CryIe than the hybrid containing one Bt gene, and the two gene hybrid would have increased potential for managing or delaying the evolution of ACB resistance to Bt corn plants.

Preclinical Evaluation of Efficacy and Safety of an Improved Lentiviral Vector for the Treatment of β-Thalassemia and Sickle Cell Disease

PubMed Central

Negre, Olivier; Bartholomae, Cynthia; Beuzard, Yves; Cavazzana, Marina; Christiansen, Lauryn; Courne, Céline; Deichmann, Annette; Denaro, Maria; de Dreuzy, Edouard; Finer, Mitchell; Fronza, Raffaele; Gillet-Legrand, Béatrix; Joubert, Christophe; Kutner, Robert; Leboulch, Philippe; Maouche, Leïla; Paulard, Anaïs; Pierciey, Francis J.; Rothe, Michael; Ryu, Byoung; Schmidt, Manfred; von Kalle, Christof; Payen, Emmanuel; Veres, Gabor

2015-01-01

A previously published clinical trial demonstrated the benefit of autologous CD34+ cells transduced with a self-inactivating lentiviral vector (HPV569) containing an engineered β-globin gene (βA-T87Q-globin) in a subject with β-thalassemia major. This vector has been modified to increase transduction efficacy without compromising safety. In vitro analyses indicated that the changes resulted in both increased vector titers (3 to 4 fold) and increased transduction efficacy (2 to 3 fold). An in vivo study in which 58 β-thalassemic mice were transplanted with vector- or mock-transduced syngenic bone marrow cells indicated sustained therapeutic efficacy. Secondary transplantations involving 108 recipients were performed to evaluate long-term safety. The six month study showed no hematological or biochemical toxicity. Integration site (IS) profile revealed an oligo/polyclonal hematopoietic reconstitution in the primary transplants and reduced clonality in secondary transplants. Tumor cells were detected in the secondary transplant mice in all treatment groups (including the control group), without statistical differences in the tumor incidence. Immunohistochemistry and quantitative PCR demonstrated that tumor cells were not derived from transduced donor cells. This comprehensive efficacy and safety data provided the basis for initiating two clinical trials with this second generation vector (BB305) in Europe and in the USA in patients with β-thalassemia major and sickle cell disease. PMID:25429463

Massage Therapy in Children with Asthma: A Systematic Review and Meta-Analysis.

PubMed

Wu, Ji; Yang, Xi-Wen; Zhang, Ming

2017-01-01

To systematically evaluate the efficacy of massage, a traditional treatment method of traditional Chinese medicine on children with asthma. Literatures from 5 databases using the date ranging from 1 January, 1990, to 13 December, 2016, were reviewed, which were all randomized controlled trials evaluating the efficacy on children with asthma and effect on lung function mainly by massage therapy. 14 researches with 1299 patients were included in the meta-analysis. Compared with control group, a better efficacy was found in treatment group, which focused on massage therapy. Compared with control group, there was remarkable increase on FEV1 as well as PEF in treatment group. All studies have shown that massage therapy has a significantly positive effect on children with asthma, improves the pulmonary function parameters of large airway, reduces the plasma concentrations of PAF and prostaglandin, and increases the levels of PAF-AH and DP1; therefore, it greatly improves pulmonary function. However, the limited research designs of included studies lead to high risk of bias. More randomized controlled trials with better methodological quality are needed to further confirm the effectiveness of massage.

A field efficacy evaluation of emamectin benzoate for the control of sea lice on Atlantic salmon.

PubMed

Armstrong, R; MacPhee, D; Katz, T; Endris, R

2000-08-01

This study evaluated the efficacy of emamectin benzoate, 0.2% aquaculture premix, against sea lice on Atlantic salmon in eastern Canada. Salmon pens received either emamectin benzoate, orally, in feed at 50 micrograms/kg body weight/day for 7 consecutive days, or the same diet with no added medication. The site veterinarian had the option of administering a bath treatment with azamethiphos to any pen in the trial. The mean number of lice per fish was lower (P < 0.05) in the experimental group when measured 1, 3, 4, and 6 weeks after the start of medication. Treatment efficacy was 70%, 88%, 95%, and 61%, respectively. Three azamethiphos bath treatments were applied to each control pen during the trial, while the treatment pens received no bath treatment. No gravid female parasites were observed on any fish in the treatment group, while these life stages were observed on fish in the control group. Orally administered emamectin benzoate was palatable and highly effective for control of sea lice on salmon.

A field efficacy evaluation of emamectin benzoate for the control of sea lice on Atlantic salmon.

PubMed Central

Armstrong, R; MacPhee, D; Katz, T; Endris, R

2000-01-01

This study evaluated the efficacy of emamectin benzoate, 0.2% aquaculture premix, against sea lice on Atlantic salmon in eastern Canada. Salmon pens received either emamectin benzoate, orally, in feed at 50 micrograms/kg body weight/day for 7 consecutive days, or the same diet with no added medication. The site veterinarian had the option of administering a bath treatment with azamethiphos to any pen in the trial. The mean number of lice per fish was lower (P < 0.05) in the experimental group when measured 1, 3, 4, and 6 weeks after the start of medication. Treatment efficacy was 70%, 88%, 95%, and 61%, respectively. Three azamethiphos bath treatments were applied to each control pen during the trial, while the treatment pens received no bath treatment. No gravid female parasites were observed on any fish in the treatment group, while these life stages were observed on fish in the control group. Orally administered emamectin benzoate was palatable and highly effective for control of sea lice on salmon. PMID:10945125

Clinical efficacy of edaravone for the treatment of amyotrophic lateral sclerosis.

PubMed

Sawada, Hideyuki

2017-05-01

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease. Although the pathogenesis remains unresolved, oxidative stress is known to play a pivotal role. Edaravone works in the central nervous system as a potent scavenger of oxygen radicals. In ALS mouse models, edaravone suppresses motor functional decline and nitration of tyrosine residues in the cerebrospinal fluid. Areas covered: Three clinical trials, one phase II open-label trial, and two phase III placebo-control randomized trials were reviewed. In all trials, the primary outcome measure was the changes in scores on the revised ALS functional rating scale (ALSFRS-R) to evaluate motor function of patients. Expert opinion: The phase II open label trial suggested that edaravone is safe and effective in ALS, markedly reducing 3-nitrotyrosine levels in the cerebrospinal fluid. One of the two randomized controlled trials showed beneficial effects in ALSFRS-R, although the differences were not significant. The last trial demonstrated that edaravone provided significant efficacy in ALSFRS-R scores over 24 weeks where concomitant use of riluzole was permitted. Eligibility was restricted to patients with a relatively short disease duration and preserved vital capacity. Therefore, combination therapy with edaravone and riluzole should be considered earlier.

Art participation for psychosocial wellbeing during stroke rehabilitation: a feasibility randomised controlled trial.

PubMed

Morris, Jacqui H; Kelly, Chris; Joice, Sara; Kroll, Thilo; Mead, Gillian; Donnan, Peter; Toma, Madalina; Williams, Brian

2017-08-30

To examine the feasibility of undertaking a pragmatic single-blind randomised controlled trial (RCT) of a visual arts participation programme to evaluate effects on survivor wellbeing within stroke rehabilitation. Stroke survivors receiving in-patient rehabilitation were randomised to receive eight art participation sessions (n = 41) or usual care (n = 40). Recruitment, retention, preference for art participation and change in selected outcomes were evaluated at end of intervention outcome assessment and three-month follow-up. Of 315 potentially eligible participants 81 (29%) were recruited. 88% (n = 71) completed outcome and 77% (n = 62) follow-up assessments. Of eight intervention group non-completers, six had no preference for art participation. Outcome completion varied between 97% and 77%. Running groups was difficult because of randomisation timing. Effectiveness cannot be determined from this feasibility study but effects sizes suggested art participation may benefit emotional wellbeing, measured on the positive and negative affect schedule, and self-efficacy for Art (d = 0.24-0.42). Undertaking a RCT of art participation within stroke rehabilitation was feasible. Art participation may enhance self-efficacy and positively influence emotional wellbeing. These should be outcomes in a future definitive trial. A cluster RCT would ensure art groups could be reliably convened. Fewer measures, and better retention strategies are required. Implications for Rehabilitation This feasibility randomised controlled trial (RCT) showed that recruiting and retaining stroke survivors in an RCT of a visual arts participation intervention within stroke rehabilitation was feasible. Preference to participate in art activities may influence recruitment and drop-out rates, and should be addressed and evaluated fully. Art participation as part of rehabilitation may improve some aspects of post-stroke wellbeing, including positive affect and self-efficacy for art. A future definitive cluster RCT would facilitate full evaluation of the value art participation can add to rehabilitation.

Efficacy of pre-exercise low-level laser therapy on isokinetic muscle performance in individuals with type 2 diabetes mellitus: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes. Methods/Design A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109. Discussion The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index – normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2. Data will be published after the study is completed. PMID:24716713

Efficacy of pre-exercise low-level laser therapy on isokinetic muscle performance in individuals with type 2 diabetes mellitus: study protocol for a randomized controlled trial.

PubMed

Gomes, Cid André Fidelis de Paula; Leal-Junior, Ernesto Cesar Pinto; Biasotto-Gonzalez, Daniela Aparecida; El-Hage, Yasmin; Politti, Fabiano; Gonzalez, Tabajara de Oliveira; Dibai-Filho, Almir Vieira; de Oliveira, Adriano Rodrigues; Frigero, Marcelo; Antonialli, Fernanda Colella; Vanin, Adriane Aver; de Tarso Camillo de Carvalho, Paulo

2014-04-09

Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes. A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109. The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index - normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2. Data will be published after the study is completed.

Cognitive-behavioral therapy for body dysmorphic disorder: a review of its efficacy

PubMed Central

Prazeres, Angélica M; Nascimento, Antônio L; Fontenelle, Leonardo F

2013-01-01

The aim of this study was to review the efficacy of different methods of cognitive and/or behavioral therapies used to treat body dysmorphic disorder. We evaluated all case series, open studies, controlled trials, and meta-analyses of cognitive and/or behavioral treatment approaches to body dysmorphic disorder published up to July 2012, identified through a search in the PubMed/Medline, PsycINFO, ISI Web of Knowledge, and Scopus databases. Our findings indicate that individual and group cognitive behavioral therapies are superior to waiting list for the treatment of body dysmorphic disorder. While the efficacy of cognitive therapy is supported by one controlled trial, utility of behavioral therapy is suggested by one open study and one controlled relapse prevention follow-up study. There is a pressing need to conduct head-to-head studies, with appropriate, active, control treatment groups, in order to examine further the efficacy of cognitive and/or behavioral therapies for body dysmorphic disorder. PMID:23467711

Efficacy and Safety of Oseltamivir in Children: Systematic Review and Individual Patient Data Meta-analysis of Randomized Controlled Trials.

PubMed

Malosh, Ryan E; Martin, Emily T; Heikkinen, Terho; Brooks, W Abdullah; Whitley, Richard J; Monto, Arnold S

2018-05-02

Oseltamivir has been used to treat children with influenza for nearly 2 decades, with treatment currently approved for infants aged ≥2 weeks. However, efficacy and safety remain controversial. Newer randomized, placebo-controlled trials (RCTs), not included in previous meta-analyses, can add to the evidence base. We conducted a systematic review to identify RCTs of oseltamivir therapy in children. We obtained individual patient data and examined protocol-defined outcomes. We then conducted a 2-stage, random-effects meta-analysis to determine the efficacy of treatment in reducing the duration of illness, estimated using differences in restricted mean survival time (RMST) by treatment group. We also examined complications and safety. We identified 5 trials that included 2561 patients in the intention-to-treat (ITT) and 1598 in the intention-to-treat infected (ITTI) populations. Overall, oseltamivir treatment significantly reduced the duration of illness in the ITTI population (RMST difference, -17.6 hours; 95% confidence interval [CI], -34.7 to -0.62 hours). In trials that enrolled patients without asthma, the difference was larger (-29.9 hours; 95% CI, -53.9 to -5.8 hours). Risk of otitis media was 34% lower in the ITTI population. Vomiting was the only adverse event with a significantly higher risk in the treatment group. Despite substantial heterogeneity in pediatric trials, we found that treatment with oseltamivir significantly reduced the duration of illness in those with influenza and lowered the risk of developing otitis media. Alternative endpoints may be required to evaluate the efficacy of oseltamivir in pediatric patients with asthma.

An education intervention to improve health literacy and decision making about supporting self-care among older Australians: a study protocol for a randomised controlled trial.

PubMed

Smith, Caroline A; Chang, Esther; Gallego, Gisselle; Balneaves, Lynda G

2017-09-26

Older Australians are high consumers of complementary and alternative medicines (CM). To help older people to take an active role in their health, we will develop and evaluate a novel educational intervention to support decision self-efficacy, and improve health literacy skills. The primary hypothesis is that participants receiving a web/DVD plus booklet intervention compared with a booklet-only group will demonstrate an increase in decision self-efficacy. This study is a randomised controlled trial. One hundred and sixty-eight people aged 65 years and older will be recruited from community settings comprising retirement villages and community groups, based in Sydney, Australia. Participants will be randomly allocated to either the education intervention delivered by the Internet or a DVD plus booklet versus a control group (booklet only). The primary outcome measure is CM decision self-efficacy. Secondary outcomes are health literacy, knowledge and attitudes, and change in health-seeking behaviour. Participants' views on the ease of using the resources, the length of the modules, the amount of information, and participant understanding of the modules will be assessed. Outcomes will be collected on completion of the intervention at 3 weeks, and at a 2-month follow up from trial entry. This trial has the potential to improve CM health literacy in older Australians. There are no educational resources designed to support decision self-efficacy and improve health literacy amongst older people related to CM. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12616000135415 . Registered on 5 February 2016.

Similar efficacy for phase I trials in comparison with DTIC for advanced malignant melanoma: an analysis of melanoma outcomes in CTEP-sponsored phase I trials 1995-2011.

PubMed

Luke, Jason J; Rubinstein, Lawrence V; Smith, Gary L; Ivy, S Percy; Harris, Pamela J

2013-04-01

After ipilimumab, vemurafenib, and interleukin-2, standard of care chemotherapy for melanoma remains dacarbazine (response rate ∼9%). Despite this, many physicians hesitate to refer patients to phase I protocols given a perceived lack of clinical benefit and potential for harm. To better understand the validity of these perceptions, the experience of all patients with melanoma treated on phase I trials sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) from 1995 to 2011 were analyzed and compared with the pooled results of six contemporary phase III trials of dacarbazine. A total of 937 patients with melanoma were treated in 148 CTEP phase I trials. The majority were men with a median of two prior therapies (46% receiving prior dacarbazine). Response and clinical benefit rates in these trials were not clinically different from those of dacarbazine (phase I: 6.3 and 26.8% vs. dacarbazine: 8.8 and 27.9%) although grades 3 and 4 toxicity was significantly higher (54 vs. 28%). Efficacy and toxicity were generally consistent within phase I subgroups (targeted agents, immunotherapies, or chemotherapeutics) though targeted therapy was associated with a lower response rate, immunotherapy with lower clinical benefit rate, and chemotherapy with higher incidence of grade 4 toxicity. Thus, the perception of limited efficacy of phase I trials for patients with melanoma was disproven, whereas the perception of toxicity was observed. However, this difference in toxicity may have been largely because of the nature of phase I vs. phase III trials (i.e. more heavily pretreated) and because of the phase I trials often being multiagent as opposed to dacarbazine alone. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

The efficacy of the Kampo medicine rikkunshito for chemotherapy-induced anorexia (RICH trial): study protocol for a randomized controlled trial.

PubMed

Inoue, Takuya; Takagi, Hironori; Owada, Yuki; Watanabe, Yuzuru; Yamaura, Takumi; Fukuhara, Mitsuro; Muto, Satoshi; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, Takeo; Osugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Yokouchi, Hiroshi; Kanazawa, Kenya; Ohbuchi, Katsuya; Fukushima, Takahisa; Munakata, Mitsuru; Suzuki, Hiroyuki

2017-10-18

Cisplatin is a key drug in lung cancer therapy. However, cisplatin is also well known to induce gastrointestinal disorders, such as chemotherapy-induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes affect patients' quality of life and make continuation of chemotherapy difficult. Anorexia is a cause of concern for patients with cancer because a persistent loss of appetite progresses to cancer cachexia. Although evidence-based management for chemotherapy has recently been established, there is room for improvement. This placebo-controlled, double-blind, randomized trial will aim to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in patients with lung cancer. Patients with lung cancer who plan to receive cisplatin-including chemotherapy will be recruited. Patients who provide written consent will be randomly allocated to receive either TJ-43 (arm A) or placebo (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators and patients will be masked to the treatment assignment throughout the trial. The primary endpoint will be evaluated as the change in dietary intake from day 0 (the day before the start of chemotherapy) to day 7 of cisplatin-including chemotherapy. The two arms of the trial will comprise 30 patients each. From November 2014, a total of 60 patients will be recruited, and recruitment for the study is planned to be complete by October 2017. This trial is designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and maintaining food intake caused by cisplatin-including chemotherapy in patients with lung cancer. Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 . Registered on 15 December 2014; the RICH trial.

Extended Safety, Immunogenicity and Efficacy of a Blood-Stage Malaria Vaccine in Malian Children: 24-Month Follow-Up of a Randomized, Double-Blinded Phase 2 Trial

PubMed Central

Laurens, Matthew B.; Thera, Mahamadou A.; Coulibaly, Drissa; Ouattara, Amed; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Traore, Idrissa; Kouriba, Bourema; Diallo, Dapa A.; Diarra, Issa; Daou, Modibo; Dolo, Amagana; Tolo, Youssouf; Sissoko, Mahamadou S.; Niangaly, Amadou; Sissoko, Mady; Takala-Harrison, Shannon; Lyke, Kirsten E.; Wu, Yukun; Blackwelder, William C.; Godeaux, Olivier; Vekemans, Johan; Dubois, Marie-Claude; Ballou, W. Ripley; Cohen, Joe; Dube, Tina; Soisson, Lorraine; Diggs, Carter L.; House, Brent; Bennett, Jason W.; Lanar, David E.; Dutta, Sheetij; Heppner, D. Gray; Plowe, Christopher V.; Doumbo, Ogobara K.

2013-01-01

Background The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allele-specific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy. Methods A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1) vaccine FMP2.1/AS02A was conducted in Bandiagara, Mali. Children aged 1–6 years were randomized in a 1∶1 ratio to receive FMP2.1/AS02A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons. Findings 400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51) against first clinical malaria episodes and 9.9% (p = 0.19) against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98) against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up. Interpretation Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against clinical malaria that waned during the second malaria season. Trial Registration Clinicaltrials.gov NCT00460525 NCT00460525 PMID:24260195

Efficacy and safety of acupuncture therapy for nerve deafness: a meta-analysis of randomized controlled trials.

PubMed

Jiang, Yuebo; Shi, Xian; Tang, Yan

2015-01-01

Acupuncture is one of the important parts of therapeutic methods in traditional Chinese medicine, and has been widely used for the treatment of nerve deafness in recent years. The current study was to evaluate the efficacy and safety of acupuncture therapy for nerve deafness compared with conventional medicine therapy. PubMed, the Chinese National Knowledge Infrastructure Database, the Chinese Science and Technology Periodical Database, the Chinese Biomedical Database, the Wanfang Database were searched for articles published to identify randomized controlled trials evaluating efficacy and side effects between acupuncture and conventional medicine therapies up to 2013/06. A total of 12 studies, including 527 patients assessed the efficacy and safety of acupuncture therapy for nerve deafness. Overall, the efficacy of acupuncture was significantly better than that of the conventional western medication (RR: 1.54, 95% CI: 1.36-1.74) or traditional Chinese medicines (RR: 1.51, 95% CI: 1.24-1.84), and the efficacy of acupuncture in combination with conventional western medication or traditional Chinese medicine was better than that of the conventional western medication alone (RR: 1.51, 95% CI: 1.29-1.77) or traditional Chinese medicine alone (RR: 1.59, 95% CI: 1.30-1.95). Based on the comparison of number of deafness patients who were completely cured, the efficacy of acupuncture in combination with traditional Chinese medicines was better than that of traditional Chinese medicine alone (RR: 4.62, 95% CI: 1.38-15.47). Acupuncture therapy can significantly improve the hearing of patients with nerve deafness, and the efficacy of acupuncture in combination with medication is superior to medication alone.

Dextromethorphan/quinidine for the treatment of pseudobulbar affect.

PubMed

Patatanian, Edna; Casselman, Jessica

2014-04-01

To evaluate the role of dextromethorphan/quinidine (DM/Q; Nuedexta™) in the treatment of pseudobulbar affect (PBA). A literature search of MEDLINE/PubMed (January 1966-June 2013) was conducted using search terms pseudobulbar affect, pathological laughing and/or crying, emotional lability, dextromethorphan, and quinidine. English language clinical trials and case reports evaluating the safety and efficacy of DM/Q in PBA were included for review. Bibliographies of all relevant articles were reviewed for additional citations. PBA, a poorly understood disorder, is characterized by involuntary crying and/or laughing. In the past, antidepressants and antiepileptics have been used off-label with mixed results. Four clinical trials have evaluated the use of DM/Q for the treatment of PBA. Although the therapeutic outcomes with DM/Q have been positive, interpretation of the published evidence is limited by small sample size and short treatment duration. Based on the data available, DM/Q may be a viable, short-term treatment alternative for PBA. Long-term safety and efficacy data are lacking.

Insulin glulisine: an evaluation of its pharmacodynamic properties and clinical application.

PubMed

Helms, Kristen L; Kelley, Kristi W

2009-04-01

To evaluate the pharmacodynamic properties, efficacy, safety, and clinical application of insulin glulisine, a rapid-acting insulin analog, in the treatment of diabetes mellitus in ambulatory and hospitalized patients. Searches were performed with the headings glulisine, insulin analog, [LysB3, GluB29] insulin, insulin glulisine, rDNA insulin, rapid-acting insulin, SoloStar, safety, efficacy, pharmacodynamics, and cost analysis within MEDLINE and PubMed, American Diabetes Association (ADA), the Food and Drug Administration (FDA), and Sanofi-aventis Pharmaceuticals (1990-August 2008). Phase 1, Phase 2, Phase 3, and postmarketing trials examining the efficacy and safety of glulisine in type 1 or type 2 diabetes were reviewed. Studies published as abstracts and the manufacturer's product information supplemented data absent from clinical trials. Insulin glulisine is a rapid-acting insulin with relative equivalence in efficacy and safety to other short- and rapid-acting insulins. Glulisine's onset of action of 20 minutes and 4-hour duration of action allow for bolus administration 15-20 minutes prior to or up to 20 minutes after meals. Clinical trials have demonstrated the safety and efficacy in adults with type 1 or type 2 diabetes. Several studies indicated a statistically significant decrease of hemoglobin A1C (A1C) with glulisine compared with regular insulin (0.10 decrease); however, no difference in A1C control was found compared with insulin aspart or lispro. Significant adverse effects appear to be limited to localized and systemic allergic reactions and hypoglycemia. Insulin glulisine is a safe and effective rapid-acting insulin analog for the treatment of adults with diabetes. Clinical benefit over other short- and rapid-acting insulin products is not established. Addition of insulin glulisine to a formulary should be based on institution-specific availability and cost differences between glulisine, lispro, and aspart in the absence of superiority of clinical efficacy or safety and data beyond 26 weeks.

An intensive social cognitive program (can do treatment) in people with relapsing remitting multiple sclerosis and low disability: a randomized controlled trial protocol.

PubMed

Jongen, Peter Joseph; Heerings, Marco; Ruimschotel, Rob; Hussaarts, Astrid; Evers, Silvia; Duyverman, Lotte; Valkenburg-Vissers, Joyce; Cornelissen, Job; Bos, Michel; van Droffelaar, Maarten; Lemmens, Wim A; Donders, Rogier; van der Zande, Anneke; Visser, Leo H

2016-05-28

In people with multiple sclerosis (MS) disabilities and limitations may negatively affect self-efficacy. Lowered self-efficacy has been associated with decreases in health-related quality of life, physical activity and cognitive performance. In an explorative observational study we found that a 3-day intensive social cognitive program (Can Do Treatment [CDT]) with the participation of support partners was followed by substantial increases in self-efficacy control and health-related quality of life 6 months after treatment in those people with MS who had relapsing remitting disease and low disability. CDT is a sociologically oriented approach, its goal is to uncover and promote existing capabilities, and the notion "stressor" is the central concept. CDT's components are plenary group sessions, small group sessions, consultations, a theatre evening, and start of the day with a joint activity. The small group sessions form the actual training. Depending on their individual goals the participants join the training groups 'Body', 'Feeling' or 'Life', to work out their aims and to reduce their stressors. The multidisciplinary team includes a psychiatrist, psychiatric nurse, neurologist, specialized MS nurse, physiotherapist, dance therapist, and a person with MS. To evaluate the (cost)effectiveness of CDT in persons with relapsing remitting MS and low disability we perform a single-centre, randomized controlled trial in 140 patients, with or without support partners. The primary outcome is self-efficacy control. The secondary outcomes are self-efficacy function, health-related quality of life, autonomy and participation, anxiety, depression, cost effectiveness and cost utility. The tertiary outcome is care-related strain to support partners. Outcomes are assessed at baseline and at 1, 3 and 6 months after CDT. This randomized controlled trial will adequately evaluate the clinical and cost effectiveness of a 3-day intensive social cognitive program in people with relapsing remitting MS and low disability, with self-efficacy control as primary outcome. Application number: 22444.

Structuring Process Evaluation to Forecast Use and Sustainability of an Intervention: Theory and Data from the Efficacy Trial for "Lunch Is in the Bag"

ERIC Educational Resources Information Center

Roberts-Gray, Cindy; Sweitzer, Sara J.; Ranjit, Nalini; Potratz, Christa; Rood, Magdalena; Romo-Palafox, Maria Jose; Byrd-Williams, Courtney E.; Briley, Margaret E.; Hoelscher, Deanna M.

2017-01-01

Background: A cluster-randomized trial at 30 early care and education centers (Intervention = 15, waitlist Control = 15) showed the "Lunch Is in the Bag" intervention increased parents' packing of fruits, vegetables, and whole grains in their preschool children's bag lunches (parent-child dyads = 351 Intervention, 282 Control). Purpose:…

Substance Use and Delinquency among Middle School Girls in Foster Care: A Three-Year Follow-Up of a Randomized Controlled Trial

ERIC Educational Resources Information Center

Kim, Hyoun K.; Leve, Leslie D.

2011-01-01

Objective: The present study evaluated the efficacy of the Middle School Success intervention (MSS) for reducing substance use and delinquency among girls in foster care, using a randomized controlled trial design. The program was designed to fill a service gap during the summer prior to the middle school transition and to prevent delinquency,…

Efficacy Trial of a Brief Cognitive-Behavioral Depression Prevention Program for High-Risk Adolescents: Effects at 1- and 2-Year Follow-Up

ERIC Educational Resources Information Center

Stice, Eric; Rohde, Paul; Gau, Jeff M.; Wade, Emily

2010-01-01

Objective: To evaluate the effects of a brief group cognitive-behavioral (CB) depression prevention program for high-risk adolescents with elevated depressive symptoms at 1- and 2-year follow-up. Method: In this indicated prevention trial, 341 at-risk youths were randomized to a group CB intervention, group supportive expressive intervention, CB…

Efficacy of a commercial probiotic relative to oxytetracycline as Gram-negative bacterial control agents in a rotifer (Brachionus plicatilis) batch culture

USDA-ARS?s Scientific Manuscript database

Two trials were conducted to evaluate two gram-negative bacterial control strategies in batch cultures of the rotifer Brachionus plicatilis. In the first trial, rotifers at an initial density of 47/mL were cultured for 5 d and dosed with a 10-mg/L solution of either oxytetracycline or a commercial p...

Evaluation of the Frails' Fall Efficacy by Comparing Treatments (EFFECT) on reducing fall and fear of fall in moderately frail older adults: study protocol for a randomised control trial.

PubMed

Kwok, Boon Chong; Mamun, Kaysar; Chandran, Manju; Wong, Chek Hooi

2011-06-18

Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo® Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo® Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline. This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments. The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme.

Clinical Efficacy and Safety of Bevacizumab Monotherapy in Patients with Metastatic Melanoma: Predictive Importance of Induced Early Hypertension

PubMed Central

Schuster, Cornelia; Eikesdal, Hans P.; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E.; Akslen, Lars A.; Straume, Oddbjørn

2012-01-01

Background VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. Trial Registration ClinicalTrials.gov NCT00139360. PMID:22719881

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials

PubMed Central

Gilbert, Peter B.; Juraska, Michal; deCamp, Allan C.; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J.; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H.; Mayer, Kenneth H.; Magaret, Craig A.; Hural, John; Kublin, James G.; Gray, Glenda; Montefiori, David C.; Gomez, Margarita M.; Burns, David N.; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S.; Mascola, John R.; Cohen, Myron; Corey, Lawrence

2017-01-01

Background Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. Methods The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Results Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. Conclusions The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention. PMID:29218117

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

PubMed

Gilbert, Peter B; Juraska, Michal; deCamp, Allan C; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H; Mayer, Kenneth H; Magaret, Craig A; Hural, John; Kublin, James G; Gray, Glenda; Montefiori, David C; Gomez, Margarita M; Burns, David N; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S; Mascola, John R; Cohen, Myron; Corey, Lawrence

2017-01-01

Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention.

Seasonal influenza vaccine efficacy and its determinants in children and non-elderly adults: a systematic review with meta-analyses of controlled trials.

PubMed

DiazGranados, Carlos A; Denis, Martine; Plotkin, Stanley

2012-12-17

The true level of influenza vaccine efficacy is controversial and many factors may influence its estimation. To estimate the efficacy of vaccination of children and non-elderly adults for the prevention of influenza and to explore the impact of type of vaccine, age, degree of strain matching, influenza type and case ascertainment methods on vaccine efficacy estimates. Medline and EmBase databases until October 2011. References of relevant articles were also reviewed. Controlled trials evaluating seasonal influenza vaccines and presenting incidence of laboratory-confirmed influenza illness were eligible. Studies exploring efficacy after experimental challenge, presenting duplicate data, employing group randomization, or focusing on special populations were excluded. The vaccine effect on influenza prevention was evaluated by calculating Mantel-Haenszel risk ratios (RR) and using random-effects models. Vaccine efficacies were calculated for each comparison as (1-RR)×100. Thirty studies were included in one or more of a total of 101 analyses, comprising 88.468 study participants. There was evidence of heterogeneity in 49% of the analyses. Summary vaccine efficacy was 65% against any strain, 78% against matched strains and 55% against not-matched strains. Both live-attenuated and inactivated vaccines showed similar levels of protection against not-matched strains (60% and 55%, respectively). Live-attenuated vaccines performed better than inactivated vaccines in children (80% versus 48%), whereas inactivated vaccines performed better than live-attenuated vaccines in adults (59% versus 39%). There was a large difference (20%) in efficacy against influenza A (69%) and influenza B (49%) types for not-matched strains. Summary estimates of vaccine efficacy were highest when ascertainment was based on culture confirmation. Influenza vaccines are efficacious, but efficacy estimates depend on many variables including type of vaccine and age of vaccinees, degree of matching of the circulating strains to the vaccine, influenza type, and methods of case ascertainment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Choosing a Control Group in Effectiveness Trials of Behavioral Drug Abuse Treatments

PubMed Central

Brigham, Gregory S.; Feaster, Daniel J.; Wakim, Paul G.; Dempsey, Catherine L.

2009-01-01

Effectiveness trials are an important step in the scientific process of developing and evaluating behavioral treatments. The focus on effectiveness research presents a different set of requirements on the research design when compared with efficacy studies. The choice of a control condition has many implications for a clinical trial's internal and external validity. The purpose of this manuscript is to provide a discussion of the issues involved in choosing a control group for effectiveness trials of behavioral interventions in substance abuse treatment. The authors provide a description of four trial designs and a discussion of the advantages and disadvantages of each. PMID:19553062

Antiviral therapeutics for the treatment of Ebola virus infection.

PubMed

Cardile, Anthony P; Downey, Lydia G; Wiseman, Perry D; Warren, Travis K; Bavari, Sina

2016-10-01

There have been significant developments in Ebola virus therapeutics. While the efficacy of several products was evaluated in the recent West Africa outbreak, a licensed treatment for EBOV disease remains elusive. Factors that negatively impacted the execution of clinical trials included an overall lack of world readiness to conduct clinical trials in an outbreak setting, ethical concerns limiting implementation of the randomized controlled trials in an outbreak setting, and a decline in case numbers by the time resources were mobilized to conduct clinical trials. We summarize relevant therapeutics that underwent clinical trials during the West Africa outbreak and highlight promising candidates under advanced development. Published by Elsevier Ltd.

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

PubMed

Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

2017-11-01

Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

Placebo use in vaccine trials: Recommendations of a WHO expert panel

PubMed Central

Rid, Annette; Saxena, Abha; Baqui, Abdhullah H.; Bhan, Anant; Bines, Julie; Bouesseau, Marie-Charlotte; Caplan, Arthur; Colgrove, James; Dhai, Ames; Gomez-Diaz, Rita; Green, Shane K.; Kang, Gagandeep; Lagos, Rosanna; Loh, Patricia; London, Alex John; Mulholland, Kim; Neels, Pieter; Pitisuttithum, Punee; Sarr, Samba Cor; Selgelid, Michael; Sheehan, Mark; Smith, Peter G.

2014-01-01

Vaccines are among the most cost-effective interventions against infectious diseases. Many candidate vaccines targeting neglected diseases in low- and middle-income countries are now progressing to large-scale clinical testing. However, controversy surrounds the appropriate design of vaccine trials and, in particular, the use of unvaccinated controls (with or without placebo) when an efficacious vaccine already exists. This paper specifies four situations in which placebo use may be acceptable, provided that the study question cannot be answered in an active-controlled trial design; the risks of delaying or foregoing an efficacious vaccine are mitigated; the risks of using a placebo control are justified by the social and public health value of the research; and the research is responsive to local health needs. The four situations are: (1) developing a locally affordable vaccine, (2) evaluating the local safety and efficacy of an existing vaccine, (3) testing a new vaccine when an existing vaccine is considered inappropriate for local use (e.g. based on epidemiologic or demographic factors), and (4) determining the local burden of disease. PMID:24768580

An Update on Renal Artery Denervation and Its Clinical Impact on Hypertensive Disease

PubMed Central

Kuang, Ye Min; Gan, Gary C. H.; Burgess, David; Denniss, Alan Robert

2015-01-01

Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials. PMID:26495305

A safety evaluation of pirfenidone for the treatment of idiopathic pulmonary fibrosis.

PubMed

Anderson, Adam; Shifren, Adrian; Nathan, Steven D

2016-07-01

Pirfenidone is a novel oral anti-fibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). Since IPF is a chronic and progressive disease most commonly encountered in an older population, therapeutic options should be not only effective, but also free from drug interactions and as safe and tolerable as possible. Comprehensive data from randomized controlled trials, meta-analyses, safety studies, and post-marketing data are available to assess the efficacy and safety of pirfenidone in the treatment of IPF. Information on efficacy, adverse events, drug tolerability and discontinuation rates both in clinical trials and real-world clinical experiences are reported. Pirfenidone has an abundance of data supporting its use in mild-to-moderate IPF. Observational evidence suggests a similar efficacy in severe IPF. In clinical trials, observational studies and real-world use, adverse events are frequent, though generally mild and well tolerated, especially with adequate patient education. Preventative strategies, along with timely and appropriate management of adverse events are critical in improving patient compliance, thereby ensuring the benefits of long-term treatment with pirfenidone.

Apatinib for metastatic breast cancer in non-clinical trial setting: Satisfying efficacy regardless of previous anti-angiogenic treatment.

PubMed

Lin, Ying; Wu, Zheng; Zhang, Jian; Hu, Xichun; Wang, Zhonghua; Wang, Biyun; Cao, Jun; Wang, Leiping

2017-06-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2. This study aimed to evaluate the efficacy and safety of apatinib in metastatic breast cancer (MBC) under non-clinical trial setting, and to study the impact of previous antiangiogenic treatment to the efficacy of apatinib. 52 MBC patients treated with apatinib under non-clinical trial setting in Fudan University Shanghai Cancer Center between January 1st 2015 and October 1st 2016 were included. All patients were included in time-to-treatment failure (TTF) analysis, while 45 patients were enrolled for progression-free survival (PFS) and overall survival (OS) analysis because 7 of the patients with treatment discontinuation due to intolerable toxicities had too short time for efficacy assessment. Impact of previous exposure to antiangiogenic treatment and other factors to patients' survival were analyzed by Log-rank analysis and Cox multivariate analysis. The median PFS, median OS, and median TTF were 4.90 (95% confidence interval [CI] 3.44 - 6.36), 10.3 (unable to calculate 95% CI), and 3.93 (95% CI 1.96 - 5.90) months, respectively. Previous treatment of bevacizumab did not affect the efficacy of apatinib. Previous exposure to anthracycline, age of 60 years or older and palmar-plantar erythrodysesthesia syndrome were independent predictors for prolonged PFS. Discontinuation of treatment was more common in age group of 60 years or older than that in younger group, although the difference was not significant. Although toxicities were generally managable, a previously unrecorded grade 3~4 adverse event of dyspnea has been observed. This study confirmed the encouraging efficacy and manageable safety of apatinib on pretreated MBC patients in non-clinical trial setting. For the first time to our knowledge, this study found that previous treatment of bevacizumab did not affect the efficacy of apatinib, and reported an undocumented severe adverse effect of dyspnea.

Feasibility and Preliminary Efficacy of the Fit4Fun Intervention for Improving Physical Fitness in a Sample of Primary School Children: A Pilot Study

ERIC Educational Resources Information Center

Eather, Narelle; Morgan, Philip J.; Lubans, David R.

2013-01-01

Objective: The primary objective of this study was to evaluate the feasibility and preliminary efficacy of a school-based physical fitness intervention (Fit4Fun) on the physical fitness and physical activity (PA) levels of primary school children. Methods: A group-randomized controlled trial with a 3-month wait-list control group was conducted in…

Efficacy and safety of adapalene gel 0.1% and 0.3% and tretinoin gel 0.05% for acne vulgaris: results of a single-center, randomized, double-blinded, placebo-controlled clinical trial on Mexican patients (skin type III-IV).

PubMed

Tirado-Sánchez, Andrés; Espíndola, Yareni Salas; Ponce-Olivera, Rosa María; Bonifaz, Alexandro

2013-06-01

The efficacy of topical retinoids is well known according to several clinical studies conducted predominantly among Caucasian patients. This study aimed to evaluate the efficacy and safety profile of adapalene and tretinoin among Mexican patients. To compare adapalene 0.1 and 0.3% and tretinoin 0.05% in Mexican subjects with acne vulgaris. We enrolled 171 patients in this single-center, randomized, double-blinded, placebo-controlled clinical trial. The patients applied on the face either adapalene 0.1%, adapalene 0.3%, tretinoin 0.05%, or placebo for 90 days and were evaluated for the reduction in total lesion counts and for the level of irritation. Tretinoin 0.05% and adapalene 0.3% were more effective than adapalene 0.1% and placebo in the reduction of both inflammatory and noninflammatory lesions. Most of adverse events to adapalene and many on tretinoin group were related to skin irritation, dry skin, scaling, pruritus, burning, and postinflammatory hyperpigmentation. Adapalene 0.3% and tretinoin 0.05% are comparable in efficacy, and adapalene 0.1% offers a better safety profile in Mexican patients. © 2013 Wiley Periodicals, Inc.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.

PubMed

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S; Wieclaw, Linda; Clifford, David B

2013-07-01

There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo. This study was a phase II, randomized, double-blind, placebo-controlled, four-period crossover multicenter study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. A total of 15 patients were enrolled from eight study sites and eight patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared with placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study dropout. Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. Wiley Periodicals, Inc.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies

PubMed Central

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S.; Wieclaw, Linda; Clifford, David B.

2014-01-01

Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. PMID:23565581

Research development of a new GnRH antagonist (Elagolix) for the treatment of endometriosis: a review of the literature.

PubMed

Alessandro, Pontis; Luigi, Nappi; Felice, Sorrentino; Maria, Paoletti Anna; Benedetto, Melis Gian; Stefano, Angioni

2017-04-01

Limitated studies have reported the efficacy of GnRH antagonist on endometriosis symptoms. The aim of our study was to review all available trials to investigate the medical treatment of endometriosis with only GnRH antagonists, with special attention to pharmacodynamic activity, safety, and efficacy. Pub Med and Sciencedirect database were searched using terms of "endometriosis treatment", "GnRH antagonist", and "Elagolix". The search was limited to clinical studies published in English. Title and abstract were screened to identify relevant articles. Five studies covering use of GnRH antagonist were found. A phase 1 study evaluated the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single dose and 7 day elagolix administration to healthy premenopausal women; two phase II studies evaluated efficacy in patient with endometriosis. Moreover, there are two Phase III clinical trials just completed. GnRH antagonists may have the advantage of oral administration and lower incidence of adverse events. Currently, only Phase II studies have been published demonstrating promising results in terms of efficacy, safety, and tolerability. From the results of the phase III studies, elagolix may become a valuable addition to the armamentarium of pharmacological agents to treat endometriosis-related pain.

Microbicide clinical trial adherence: insights for introduction.

PubMed

Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena

2013-04-08

After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.

A systematic review and meta-analysis for the adverse effects, immunogenicity and efficacy of Lyme disease vaccines: Guiding novel vaccine development.

PubMed

Badawi, Alaa; Shering, Maria; Rahman, Shusmita; Lindsay, L Robbin

2017-04-20

Lyme borreliosis (LB) is the most prevalent arthropod-borne infectious disease in North America. Currently, no vaccine is available to prevent LB in humans, although monovalent and multivalent vaccines have been developed in the past. The aim of the current study is to conduct a systematic review and meta-analysis to evaluate and compare the findings from these two classes of vaccines for their reactogenicity, immunogenicity and efficacy, in the hope this may assist in the development of future vaccines. A search strategy was developed for online databases (PubMed, Ovid MEDLINE, and Embase). Search terms used were "vaccine/vaccination", "Lyme disease/Borreliosis", "clinical trial(s)" and "efficacy". Only seven clinical trials were included to compare the results of the monovalent vaccines to those of the multivalent one. Meta-analyses were conducted to evaluate the reactogenicity and immunogenicity of the two vaccine classes. Odds ratio (OR) for LB (and 95% confidence intervals; 95% CI) were calculated for the efficacy of the monovalent vaccine from three different clinical trials at different dose schedules. Incidence of redness (local adverse effect) and fever (systemic side effect) were, respectively, 6.8- and 2.9-fold significantly lower (p < 0.05) in individuals who received multivalent vaccines compared to those receiving the monovalent one. Incidences of all other local and systemic adverse effects were non-significantly lower in the multivalent vaccine compared to the monovalent vaccines. Seroprotection was comparable among individuals who received the two vaccine classes at the 30 μg dose level. Efficacy in the prevention of LB was only evaluated for the monovalent vaccines. OR of LB ranged from 0.49 (95% CI: 0.14-0.70; p < 0.005, vs. placebo) to 0.31 (95% CI: 0.26-0.63; p < 0.005) for the initial and final doses respectively, with an overall OR of 0.4 (95% CI: 0.26-0.63, p < 0.001). The current study further validates that the monovalent and multivalent LB vaccines result in mild local side effects and self-limiting systemic adverse effects, with the multivalent vaccine slightly more tolerable than the monovalent one. Both vaccine classes were similarly highly immunogenic. A new vaccine with high safety standards, better efficacy, low cost, and public acceptance is yet to be developed. Meanwhile, personal protection limiting exposure to ticks is recommended.

Steep cut slope composting : field trials and evaluation.

DOT National Transportation Integrated Search

2011-04-01

Three different depths of compost and five compost retention techniques were tested to determine : their efficacy and cost effectiveness for increasing the establishment of native grass seedings and decreasing : erosion on steep roadside cut slopes i...

Efficacy for Psychopathology and Body Weight and Safety of Topiramate-Antipsychotic Cotreatment in Patients With Schizophrenia Spectrum Disorders: Results From a Meta-Analysis of Randomized Controlled Trials.

PubMed

Correll, Christoph U; Maayan, Lawrence; Kane, John; Hert, Marc De; Cohen, Dan

2016-06-01

To meta-analyze the efficacy and tolerability of topiramate-antipsychotic cotreatment in schizophrenia. PubMed/MEDLINE database were searched until September 5, 2015, using the keywords topiramate AND antipsych* OR neurolept* OR specific antipsychotic names. Randomized controlled trials (RCTs) of topiramate-antipsychotic cotreatment versus placebo and ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders were included. Two evaluators extracted data. Standardized mean difference (SMD), weighted mean difference (WMD), and risk ratio (RR) ± 95% CIs were calculated. In 8 RCTs, lasting a mean ± SD of 13.6 ± 4.9 weeks, 439 patients were randomized to topiramate (100-400 mg/d) versus placebo (trials = 7) or ongoing antipsychotic treatment (trial = 1). Topiramate outperformed the comparator regarding total psychopathology (trials = 6, n = 269, SMD = -0.57 [95% CI, -1.01 to -0.14], P = .01), positive symptoms (trials = 4, n = 190, SMD = -0.56 [95% CI, -1.0 to -0.11], P = .01), negative symptoms (trials = 4, n = 190, SMD = -0.62 [95% CI, -1.13 to -0.10], P = .02) general psychopathology (trials = 3, n = 179, SMD = -0.69 [95% CI, -1.27 to -0.11], P = .02), body weight (trials = 7, n = 327, WMD = -3.14 kg [95% CI, -5.55 to -0.73], P = .01), and body mass index (BMI) (trials = 4, n = 198, WMD = -1.80 [95% CI, -2.77 to -0.84], P = .0003). Topiramate's efficacy for total psychopathology and weight reduction effects were not mediated/moderated by trial duration, topiramate dose, sex, age, inpatient status, baseline Positive and Negative Syndrome Scale, or baseline BMI. Conversely, clozapine-topiramate cotreatment moderated greater efficacy, but less weight loss, compared to topiramate-nonclozapine antipsychotic combinations. All-cause discontinuation was similar between topiramate and control groups (trials = 7, RR = 1.24 [95% CI, 0.76 to 2.02], P = .39). Topiramate trended only toward more paresthesia than placebo (trials = 4, RR = 2.03 [95 % CI, 0.99 to 4.18], P = .05). Topiramate-antipsychotic cotreatment significantly reduced total, positive, negative, and general psychopathology and weight/BMI in patients with schizophrenia spectrum disorder while being well tolerated. However, larger studies are needed to confirm and extend these findings. © Copyright 2016 Physicians Postgraduate Press, Inc.

Complementary and Alternative Approaches to Pain Relief During Labor

PubMed Central

Theau-Yonneau, Anne

2007-01-01

This review evaluated the effect of complementary and alternative medicine on pain during labor with conventional scientific methods using electronic data bases through 2006 were used. Only randomized controlled trials with outcome measures for labor pain were kept for the conclusions. Many studies did not meet the scientific inclusion criteria. According to the randomized control trials, we conclude that for the decrease of labor pain and/or reduction of the need for conventional analgesic methods: (i) There is an efficacy found for acupressure and sterile water blocks. (ii) Most results favored some efficacy for acupuncture and hydrotherapy. (iii) Studies for other complementary or alternative therapies for labor pain control have not shown their effectiveness. PMID:18227907

Enhancing Clinical Trials by Incorporating Side Effects

ERIC Educational Resources Information Center

Schrag, Francis

2009-01-01

Evidence-based medicine is often seen as a model for evidence-based education, and deservedly so, but evaluators in education have been slow to adopt one of its salient features, attention to side effects. Many education evaluations focus almost exclusively on efficacy, that is on achievement test scores. Regardless of domain, all interventions…

A Group Randomized Controlled Trial Evaluating Parent Involvement in Whole-School Actions to Reduce Bullying

ERIC Educational Resources Information Center

Cross, Donna; Lester, Leanne; Pearce, Natasha; Barnes, Amy; Beatty, Shelley

2018-01-01

Parents can significantly affect children's peer relationships, including their involvement in bullying. The authors developed and evaluated ways to enhance parents' knowledge, self-efficacy, attitudes, and skills related to parent-child communication about bullying. The 3-year Friendly Schools Friendly Families whole-school intervention included…

Comparison of Stepped Care Delivery Against a Single, Empirically Validated Cognitive-Behavioral Therapy Program for Youth With Anxiety: A Randomized Clinical Trial.

PubMed

Rapee, Ronald M; Lyneham, Heidi J; Wuthrich, Viviana; Chatterton, Mary Lou; Hudson, Jennifer L; Kangas, Maria; Mihalopoulos, Cathrine

2017-10-01

Stepped care is embraced as an ideal model of service delivery but is minimally evaluated. The aim of this study was to evaluate the efficacy of cognitive-behavioral therapy (CBT) for child anxiety delivered via a stepped-care framework compared against a single, empirically validated program. A total of 281 youth with anxiety disorders (6-17 years of age) were randomly allocated to receive either empirically validated treatment or stepped care involving the following: (1) low intensity; (2) standard CBT; and (3) individually tailored treatment. Therapist qualifications increased at each step. Interventions did not differ significantly on any outcome measures. Total therapist time per child was significantly shorter to deliver stepped care (774 minutes) compared with best practice (897 minutes). Within stepped care, the first 2 steps returned the strongest treatment gains. Stepped care and a single empirically validated program for youth with anxiety produced similar efficacy, but stepped care required slightly less therapist time. Restricting stepped care to only steps 1 and 2 would have led to considerable time saving with modest loss in efficacy. Clinical trial registration information-A Randomised Controlled Trial of Standard Care Versus Stepped Care for Children and Adolescents With Anxiety Disorders; http://anzctr.org.au/; ACTRN12612000351819. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Safety and Efficacy of Rice Bran Supercritical CO2 Extract for Hair Growth in Androgenic Alopecia: A 16-Week Double-Blind Randomized Controlled Trial.

PubMed

Choi, Jae-Suk; Park, Jae Beom; Moon, Woi-Sook; Moon, Jin-Nam; Son, Sang Wook; Kim, Mi-Ryung

2015-01-01

We conducted a 16-week double-blind randomized controlled single-center trial to evaluate the safety and efficacy of dermal rice bran supercritical CO2 extract (RB-SCE) in the treatment of androgenic alopecia. Fifty alopecia patients were randomly assigned to the experimental and placebo groups. The experimental group received a dermal application of 0.5% RB-SCE (8 mL/d) to the head skin for 16 weeks while the control group received a dermal application of placebo. Changes in hair count, diameter, and density were evaluated with a Folliscope(®). Patient satisfaction was evaluated via questionnaire and clinical photographs were rated by dermatologists. The results showed that RB-SCE significantly increased hair density and hair diameter in male subjects. Patient satisfaction and the evaluation of photographs by dermatologists also confirmed the effectiveness of RB-SCE in the treatment of alopecia. No adverse reactions related to RB-SCE were reported. Therefore, RB-SCE shows promise for use in functional cosmetics and pharmaceuticals.

Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

PubMed

Yeung, Wing-Fai; Chung, Ka-Fai; Zhang, Zhang-Jin; Chan, Wai-Chi; Zhang, Shi-Ping; Ng, Roger Man-Kin; Chan, Connie Lai-Wah; Ho, Lai-Ming; Yu, Yee-Man; Lao, Li-Xing

2017-03-31

Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. ClinicalTrials.gov NCT02475538 .

Is lavender an anxiolytic drug? A systematic review of randomised clinical trials.

PubMed

Perry, R; Terry, R; Watson, L K; Ernst, E

2012-06-15

Lavender (Lavandula angustifolia) is often recommended for stress/anxiety relief and believed to possess anxiolytic effects. To critically evaluate the efficacy/effectiveness of lavender for the reduction of stress/anxiety. Seven electronic databases were searched to identify all relevant studies. All methods of lavender administration were included. Data extraction and the assessment of the methodological quality of all included trials were conducted by two independent reviewers. Fifteen RCTs met the inclusion criteria. Two trials scored 4 points on the 5-point Jadad scale, the remaining 13 scored two or less. Results from seven trials appeared to favour lavender over controls for at least one relevant outcome. Methodological issues limit the extent to which any conclusions can be drawn regarding the efficacy/effectiveness of lavender. The best evidence suggests that oral lavender supplements may have some therapeutic effects. However, further independent replications are needed before firm conclusions can be drawn. Copyright © 2012 Elsevier GmbH. All rights reserved.

An open treatment trial of venlafaxine for elderly patients with dysthymic disorder.

PubMed

Devanand, D P; Juszczak, Nicole; Nobler, Mitchell S; Turret, Nancy; Fitzsimons, Linda; Sackeim, Harold A; Roose, Steven P

2004-12-01

Treatment response and side effects of venlafaxine were evaluated in an open-label trial of elderly outpatients with dysthymic disorder (DD). Patients received flexible dose (up to 300 mg/d) venlafaxine (Effexor XR) for 12 weeks. Of 23 study patients, 18 completed the trial. Fourteen (60.9%) were responders in intent-to-treat analyses with the last observation carried forward, and 77.8% were responders in completer analyses. Nearly half the sample (47.8%) met criteria for remission. In the intent-to-treat sample, increased severity of depression at baseline was associated with superior response, and the presence of cardiovascular disease was associated with poorer response. Venlafaxine open-label treatment was associated with fairly high response rates and generally good tolerability in elderly patients with DD. These results indicate that in elderly patients with DD, placebo-controlled trials of a dual reuptake inhibitor such as venlafaxine would be needed to assess its efficacy or to compare its efficacy to that of other antidepressants.

Randomized Trial of Hypnosis as a Pain and Symptom Management Strategy in Adults with Sickle Cell Disease

PubMed Central

Wallen, Gwenyth R; Middleton, Kimberly R; Ames, Nancy; Brooks, Alyssa T; Handel, Daniel

2014-01-01

Sickle cell disease (SCD) is the most common genetic disease in African-Americans, characterized by recurrent painful vaso-occlusive crises. Medical therapies for controlling or preventing crises are limited because of efficacy and/or toxicity. This is a randomized, controlled, single-crossover protocol of hypnosis for managing pain in SCD patients. Participants receive hypnosis from a trained hypnosis therapist followed by six weeks of self-hypnosis using digital media. Those in the control arm receive SCD education followed by a six-week waiting period before crossing over to the hypnosis arm of the study. Outcome measures include assessments of pain (frequency, intensity and quality), anxiety, coping strategies, sleep, depression, and health care utilization. To date, there are no published randomized, controlled trials evaluating the efficacy of hypnosis on SCD pain modulation in adults. Self-hypnosis for pain management may be helpful in modulating chronic pain, improving sleep quality, and decreasing use of narcotics in patients with SCD. TRIAL REGISTRATION ClinicalTrials.gov: NCT00393250 PMID:25520557

Evaluation of a corticotropin releasing hormone type 1 receptor antagonist in women with posttraumatic stress disorder: study protocol for a randomized controlled trial.

PubMed

Dunlop, Boadie W; Rothbaum, Barbara O; Binder, Elisabeth B; Duncan, Erica; Harvey, Philip D; Jovanovic, Tanja; Kelley, Mary E; Kinkead, Becky; Kutner, Michael; Iosifescu, Dan V; Mathew, Sanjay J; Neylan, Thomas C; Kilts, Clinton D; Nemeroff, Charles B; Mayberg, Helen S

2014-06-21

Pharmacologic treatment options for posttraumatic stress disorder (PTSD) are limited in number and effectiveness. Medications currently in use to treat PTSD were originally approved based on their efficacy in other disorders, such as major depression. Substantial research in PTSD suggests that increased activity of corticotropin releasing hormone (CRH)-containing circuits are involved in the pathophysiology of the disease. This Phase II trial aims to evaluate the efficacy of a CRH type 1 receptor (CRHR1) antagonist in the treatment of PTSD. Currently untreated adult women, ages 18 to 65 years, with a primary psychiatric diagnosis of PTSD of at least 3 months' duration, are being enrolled in a parallel-group, double-blind, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of GSK561679, a novel CRHR1 receptor antagonist. GSK561679 (or matching placebo) is prescribed at a fixed dose of 350 mg nightly for six weeks. The primary trial hypothesis is that GSK561679 will reduce symptoms of PTSD, as measured by the Clinician-Administered PTSD Scale (CAPS), significantly more than placebo after six weeks of treatment. Putative biological markers of PTSD which may influence treatment response are measured prior to randomization and after five weeks' exposure to the study medication, including: fear conditioning and extinction using psychophysiological measures; variants of stress-related genes and gene expression profiles; and indices of HPA axis reactivity. In addition, the impact of PTSD and treatment on neuropsychological performance and functional capacity are assessed at baseline and after the fifth week of study medication. After completion of the six-week double blind treatment period, subjects enter a one-month follow-up period to monitor for sustained response and resolution of any adverse effects. Considerable preclinical and human research supports the hypothesis that alterations in central nervous system CRH neuronal activity are a potential mediator of PTSD symptoms. This study is the first to assess the efficacy of a specific antagonist of a CRH receptor in the treatment of PTSD. Furthermore, the biological and neuropsychological measures included in this trial will substantially inform our understanding of the mechanisms of PTSD. Clinicaltrials.gov Identifier: NCT01018992.Registered 6 November 2009. First patient randomized 14 January 2010.

Use of ClinicalTrials.gov to estimate condition-specific nocebo effects and other factors affecting outcomes of analgesic trials.

PubMed

Cepeda, M Soledad; Lobanov, Victor; Berlin, Jesse A

2013-04-01

ClinicalTrials.gov is a registry and results database of federally and privately supported clinical trials conducted worldwide. We sought to answer: what are the characteristics of pain trials; how frequently are these trials stopped and why; what is the magnitude of attrition due to lack of efficacy or adverse events; and whether the withdrawal rates depend on pain syndrome. To facilitate this and subsequent studies, we have developed a system called Sherlock that automatically downloads data from ClinicalTrials.gov into a relational database. We included pain interventional trials. To evaluate attrition, we restricted consideration to prospective randomized, parallel, double-blind, placebo-controlled trials. Of the 82,867 trials, 6% reported results and 5.6% terminated before the planned number of subjects was accrued. Of these early terminations, 38% were due to enrollment difficulties. In the placebo arms, 3.8% of participants withdrew due to lack of efficacy and 4.9% due to adverse events, with proportions differing among pain conditions. Compared with migraine trials, in fibromyalgia trials 5.1% more participants withdrew due to lack of efficacy (95% confidence interval [CI], 2.5-7.8%), and 6.4% more withdrew due to adverse events (95% CI, 4.3-8.6%). Nonsteroidal anti-inflammatory drugs were the treatment class with the lowest adverse events withdrawals. Recruitment challenges account for the largest proportion of noncompleted trials. Attrition rates differ across pain conditions. Migraine studies had the lowest withdrawal rate. Tools like Sherlock facilitate conducting research in the ClinicalTrials.gov registry. ClinicalTrials.gov registry enables researchers to get a snapshot of a specific field and observe changes over time in trial design, including numbers of subjects accrued, and it can inform clinical trial design. We learned that recruitment challenges account for the largest proportion of noncompleted trials, attrition rates differed across pain conditions, and migraine studies had the lowest withdrawal rate. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Using Outcomes to Analyze Patients Rather than Patients to Analyze Outcomes: A Step toward Pragmatism in Benefit:risk Evaluation.

PubMed

Evans, Scott R; Follmann, Dean

2016-01-01

In the future, clinical trials will have an increased emphasis on pragmatism, providing a practical description of the effects of new treatments in realistic clinical settings. Accomplishing pragmatism requires better summaries of the totality of the evidence in ways that clinical trials consumers---patients, physicians, insurers---find transparent and allow for informed benefit:risk decision-making. The current approach to the analysis of clinical trials is to analyze efficacy and safety separately and then combine these analyses into a benefit:risk assessment. Many assume that this will effectively describe the impact on patients. But this approach is suboptimal for evaluating the totality of effects on patients. We discuss methods for benefit:risk assessment that have greater pragmatism than methods that separately analyze efficacy and safety. These include the concepts of within-patient analyses and composite benefit:risk endpoints with a goal of understanding how to analyze one patient before trying to figure out how to analyze many. We discuss the desirability of outcome ranking (DOOR) and introduce the partial credit strategy using an example in a clinical trial evaluating the effects of a new antibiotic. As part of the example we introduce a strategy to engage patients as a resource to inform benefit:risk analyses consistent with the goal of measuring and weighing outcomes that are most important from the patient's perspective. We describe a broad vision for the future of clinical trials consistent with increased pragmatism. Greater focus on using endpoints to analyze patients rather than patients to analyze endpoints particularly in late-phase/stage clinical trials is an important part of this vision.

In Silico Evaluation of Pharmacokinetic Optimization for Antimitogram-Based Clinical Trials.

PubMed

Haviari, Skerdi; You, Benoît; Tod, Michel

2018-04-01

Antimitograms are prototype in vitro tests for evaluating chemotherapeutic efficacy using patient-derived primary cancer cells. These tests might help optimize treatment from a pharmacodynamic standpoint by guiding treatment selection. However, they are technically challenging and require refinements and trials to demonstrate benefit to be widely used. In this study, we performed simulations aimed at exploring how to validate antimitograms and how to complement them by pharmacokinetic optimization. A generic model of advanced cancer, including pharmacokinetic-pharmacodynamic monitoring, was used to link dosing schedules with progression-free survival (PFS), as built from previously validated modules. This model was used to explore different possible situations in terms of pharmacokinetic variability, pharmacodynamic variability, and antimitogram performance. The model recapitulated tumor dynamics and standalone therapeutic drug monitoring efficacy consistent with published clinical results. Simulations showed that combining pharmacokinetic and pharmacodynamic optimization should increase PFS in a synergistic fashion. Simulated data were then used to compute required clinical trial sizes, which were 30% to 90% smaller when pharmacokinetic optimization was added to pharmacodynamic optimization. This improvement was observed even when pharmacokinetic optimization alone exhibited only modest benefit. Overall, our work illustrates the synergy derived from combining antimitograms with therapeutic drug monitoring, permitting a disproportionate reduction of the trial size required to prove a benefit on PFS. Accordingly, we suggest that strategies with benefits too small for standalone clinical trials could be validated in combination in a similar manner. Significance: This work offers a method to reduce the number of patients needed for a clinical trial to prove the hypothesized benefit of a drug to progression-free survival, possibly easing opportunities to evaluate combinations. Cancer Res; 78(7); 1873-82. ©2018 AACR . ©2018 American Association for Cancer Research.

Using Outcomes to Analyze Patients Rather than Patients to Analyze Outcomes: A Step toward Pragmatism in Benefit:risk Evaluation

PubMed Central

Evans, Scott R.; Follmann, Dean

2016-01-01

In the future, clinical trials will have an increased emphasis on pragmatism, providing a practical description of the effects of new treatments in realistic clinical settings. Accomplishing pragmatism requires better summaries of the totality of the evidence in ways that clinical trials consumers---patients, physicians, insurers---find transparent and allow for informed benefit:risk decision-making. The current approach to the analysis of clinical trials is to analyze efficacy and safety separately and then combine these analyses into a benefit:risk assessment. Many assume that this will effectively describe the impact on patients. But this approach is suboptimal for evaluating the totality of effects on patients. We discuss methods for benefit:risk assessment that have greater pragmatism than methods that separately analyze efficacy and safety. These include the concepts of within-patient analyses and composite benefit:risk endpoints with a goal of understanding how to analyze one patient before trying to figure out how to analyze many. We discuss the desirability of outcome ranking (DOOR) and introduce the partial credit strategy using an example in a clinical trial evaluating the effects of a new antibiotic. As part of the example we introduce a strategy to engage patients as a resource to inform benefit:risk analyses consistent with the goal of measuring and weighing outcomes that are most important from the patient’s perspective. We describe a broad vision for the future of clinical trials consistent with increased pragmatism. Greater focus on using endpoints to analyze patients rather than patients to analyze endpoints particularly in late-phase/stage clinical trials is an important part of this vision. PMID:28435515

Cognitive and memory training in adults at risk of dementia: A Systematic Review

PubMed Central

2011-01-01

Background Effective non-pharmacological cognitive interventions to prevent Alzheimer's dementia or slow its progression are an urgent international priority. The aim of this review was to evaluate cognitive training trials in individuals with mild cognitive impairment (MCI), and evaluate the efficacy of training in memory strategies or cognitive exercises to determine if cognitive training could benefit individuals at risk of developing dementia. Methods A systematic review of eligible trials was undertaken, followed by effect size analysis. Cognitive training was differentiated from other cognitive interventions not meeting generally accepted definitions, and included both cognitive exercises and memory strategies. Results Ten studies enrolling a total of 305 subjects met criteria for cognitive training in MCI. Only five of the studies were randomized controlled trials. Meta-analysis was not considered appropriate due to the heterogeneity of interventions. Moderate effects on memory outcomes were identified in seven trials. Cognitive exercises (relative effect sizes ranged from .10 to 1.21) may lead to greater benefits than memory strategies (.88 to -1.18) on memory. Conclusions Previous conclusions of a lack of efficacy for cognitive training in MCI may have been influenced by not clearly defining the intervention. Our systematic review found that cognitive exercises can produce moderate-to-large beneficial effects on memory-related outcomes. However, the number of high quality RCTs remains low, and so further trials must be a priority. Several suggestions for the better design of cognitive training trials are provided. PMID:21942932

A Systematic Review of NMDA Receptor Antagonists for Treatment of Neuropathic Pain in Clinical Practice.

PubMed

Aiyer, Rohit; Mehta, Neel; Gungor, Semih; Gulati, Amitabh

2018-05-01

To investigate the efficacy of N-methyl-D-aspartate receptor (NMDAR) antagonists for neuropathic pain (NeuP) and review literature to determine if specific pharmacologic agents provide adequate NeuP relief. Literature was reviewed on PubMed using a variety of key words for 8 NMDAR antagonists. These key words include: "Ketamine and Neuropathy," "Ketamine and Neuropathic Pain," "Methadone and Neuropathy," "Methadone and Neuropathic Pain," "Memantine and Neuropathic pain," "Memantine and Neuropathy," "Amantadine and Neuropathic Pain," "Amantadine and Neuropathy," "Dextromethorphan and Neuropathic Pain," "Dextromethorphan and Neuropathy," "Carbamazepine and Neuropathic Pain," "Carbamazepine and Neuropathy," "Valproic Acid and Neuropathy," "Valproic Acid and Neuropathic Pain," "Phenytoin and Neuropathy," and "Phenytoin and Neuropathic Pain." With the results, the papers were reviewed using the PRISMA (Preferred Reporting in Systematic and Meta-Analyses) guideline. A total of 58 randomized controlled trials were reviewed among 8 pharmacologic agents, which are organized by date and alphabetical order. Of the trials for ketamine, 15 showed some benefit for analgesia. Methadone had 3 positive trials, while amantadine and memantine each only had 2 trials showing NeuP analgesic properties. Dextromethorphan and valproic acid both had 4 randomized controlled trials that showed some NeuP treatment benefit while carbamazepine had over 8 trials showing efficacy. Finally, phenytoin only had 1 trial that showed clinical response in treatment. There are a variety of NMDAR antagonist agents that should be considered for treatment of NeuP. Nevertheless, continued and further investigation of the 8 pharmacologic agents is needed to continue to evaluate their efficacy for treatment of NeuP.

The Use of Cannabinoids in Treating Dementia.

PubMed

Weier, Megan; Hall, Wayne

2017-08-01

To review and summarise the current evidence on the safety and efficacy of using cannabinoids to treat behavioural and neuropsychiatric symptoms of dementia. Two randomised controlled trials testing a synthetic form of tetrahydrocannabinol have shown that while well tolerated, there was no significant therapeutic effect, based on changes to scores on the neuropsychiatric inventory (NPI). Case reports and open label trials have indicated that there may be some therapeutic benefit of adding synthetic cannabinoids as an adjunctive therapy to reduce agitation, aberrant motor behaviour and nighttime behaviour. More well-controlled clinical trials in older populations with varying severity of dementia are needed to evaluate the effectiveness of cannabinoids in treating behaviour symptoms of dementia. We provide suggestions for designing such trials and evaluating possible adverse effects of cannabinoids on cognitive and neuropsychiatric functioning.

Evaluation of Safety and Efficacy of Qinming8631 DR Implantable Cardiac Pacemaker in Chinese Patients: A Prospective, Multicenter, Randomized Controlled Trial of the First Domestically Developed Pacemaker of China.

PubMed

Xiang, Mei-Xiang; Wang, Dong-Qi; Xu, Jing; Zhang, Zheng; Hu, Jian-Xin; Wang, Dong-Mei; Gu, Xiang; Liu, He-Ping; Guo, Tao; Yang, Xiang-Jun; Ling, Feng; Lin, Jia-Feng; Cai, Shang-Lang; Zhu, Guo-Bin; Wang, Jian-An

2016-11-20

High cost of imported pacemakers is a main obstacle for Chinese patients suffering from bradyarrhythmia, and a domestically developed pacemaker will help lower the burden. This study aimed to evaluate the safety and efficacy of Qinming8631 DR (Qinming Medical, Baoji, China), the first domestically developed dual-chamber pacemaker of China, compared with a commercially available pacemaker Talos DR (Biotronik, Berlin, Germany) in Chinese patients. A prospective randomized trial was conducted at 14 centers in China. Participants were randomized into trial (Qinming8631 DR) and control (Talos DR) groups. Parameters of the pacing systems were collected immediately after device implantation and during follow-ups. The effective pacing rate at 6-month follow-up was recorded as the primary end point. Electrical properties, magnet response, single- and double-pole polarity conversion, rate response function, and adverse events of the pacing system were analyzed. The Cochran-Mantel-Haenszel Chi-square test, paired t-test, and Wilcoxon signed-rank test were used for measuring primary qualitative outcomes and comparing normally and abnormally distributed measurement data. A total of 225 patients with a diagnosis of bradyarrhythmia and eligible for this study were randomly enrolled into the trial (n = 113) and control (n = 112) groups. They underwent successful pacemaker implantation with acceptable postoperative pacing threshold and sensitivity. Effective pacing rates of trial and control groups were comparable both in the full analysis set and the per protocol set (81.4% vs. 79.5%, P = 0.712 and 95.4% vs. 89.5%, P = 0.143, respectively). In both data sets, noninferiority of the trial group was above the predefined noninferiority limit(-9.5%). This study established the noninferiority of Qinming8631 DR to Talos DR. The safety and efficacy of Qinming8631 DR pacemaker were comparable to those of Talos DR in treating patients with cardiac bradyarrhythmia.

Antidepressant Efficacy for Depression in Children and Adolescents: Industry- and NIMH-Funded Studies.

PubMed

Walkup, John T

2017-05-01

Significant controversy surrounds the efficacy of the newer antidepressants for children and adolescents with depression. The controversy largely hinges on meta-analyses of studies that suggest that antidepressants are minimally effective, not effective, or equivalent to placebo. In this review, the author discusses several scientific and clinical complexities that are important to understand in reviewing the antidepressant literature: the strengths and weaknesses of meta-analyses; the scientific and regulatory context for the large number of antidepressant trials in the late 1990s and early 2000s; and the distinction between a negative trial, where the treatment does not demonstrate efficacy, and a failed trial, where methodological problems make it impossible to draw any conclusion about efficacy. It is the premise of this review that meta-analyses that include the large number of industry-sponsored antidepressant trials distort the picture of antidepressant efficacy for teen depression. Industry-sponsored child and adolescent depression trials suffer from a number of implementation challenges and should be considered failed trials that are largely uninformative and not eligible to be included in efficacy meta-analyses. In contrast to the industry-sponsored trials, depression trials funded by the National Institute of Mental Health (NIMH) (N=2) are characterized by many methodological strengths, lower placebo response rates (30%-35%), and meaningful between-group differences (25%-30%) that support antidepressant efficacy. The NIMH-funded trials, taken together with the demonstrated efficacy of the serotonin reuptake inhibitors for childhood-onset obsessive-compulsive disorder and the anxiety disorders, suggest a broad and important role for antidepressant medications in pediatric internalizing conditions.

"FIND Technology": investigating the feasibility, efficacy and safety of controller-free interactive digital rehabilitation technology in an inpatient stroke population: study protocol for a randomized controlled trial.

PubMed

Bird, M L; Cannell, J; Callisaya, M L; Moles, E; Rathjen, A; Lane, K; Tyson, A; Smith, S

2016-04-16

Stroke results in significant disability, which can be reduced by physical rehabilitation. High levels of repetition and activity are required in rehabilitation, but patients are typically sedentary. Using clinically relevant and fun computer games may be one way to achieve increased activity in rehabilitation. A single-blind randomized controlled trial will be conducted to evaluate the feasibility, efficacy and safety of novel stroke-specific rehabilitation software. This software uses controller-free client interaction and inertial motion sensors. Elements of feasibility include recruitment into the trial, ongoing participation (adherence and dropout), perceived benefit, enjoyment and ease of use of the games. Efficacy will be determined by measuring activity and using upper-limb tasks as well as measures of balance and mobility. The hypothesis that the intervention group will have increased levels of physical activity within rehabilitation and improved physical outcomes compared with the control group will be tested. Results from this study will provide a basis for discussion of feasibility of this interactive video technological solution in an inpatient situation. Differences in activity levels between groups will be the primary measure of efficacy. It will also provide data on measures of upper-limb function, balance and mobility. ACTRN12614000427673 . Prospectively registered 17 April 2014.

Beyond Standard Therapy: Drugs Under Investigation for The Treatment of Gastrointestinal Stromal Tumor

PubMed Central

Alturkmani, Hani J; Pessetto, Ziyan Y; Godwin, Andrew K

2015-01-01

Introduction Gastrointestinal stromal tumor (GIST) is the most common non-epithelial malignancy of the GI tract. With the discovery of KIT and later PDGFRA gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST. Areas covered This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans. Expert opinion It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival. PMID:26098203

Malaria Diagnostics in Clinical Trials

PubMed Central

Murphy, Sean C.; Shott, Joseph P.; Parikh, Sunil; Etter, Paige; Prescott, William R.; Stewart, V. Ann

2013-01-01

Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484

A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with systolic heart failure: rationale, design, and baseline patient characteristics.

PubMed

Abraham, William T; Burkhoff, Daniel; Nademanee, Koonlawee; Carson, Peter; Bourge, Robert; Ellenbogen, Kenneth A; Parides, Michael; Kadish, Alan

2008-10-01

Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the cardiac absolute refractory period that enhance the strength of cardiac muscular contraction. Prior research in experimental and human heart failure has shown that CCM signals normalize phosphorylation of key proteins and expression of genes coding for proteins involved in regulation of calcium cycling and contraction. The results of prior clinical studies of CCM have supported its safety and efficacy. A large-scale clinical study, the FIX-HF-5 study, is currently underway to test the safety and efficacy of this treatment. In this article, we provide an overview of the system used to deliver CCM signals, the implant procedure, and the details and rationale of the FIX-HF-5 study design. Baseline characteristics for patients randomized in this trial are also presented.

Designing malaria vaccines to circumvent antigen variability✩

PubMed Central

Ouattara, Amed; Barry, Alyssa E.; Dutta, Sheetij; Remarque, Edmond J.; Beeson, James G.; Plowe, Christopher V.

2016-01-01

Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines. PMID:26475447

Efficacy of Curcuma for Treatment of Osteoarthritis.

PubMed

Perkins, Kimberly; Sahy, William; Beckett, Robert D

2017-01-01

The objective of this review is to identify, summarize, and evaluate clinical trials to determine the efficacy of curcuma in the treatment of osteoarthritis. A literature search for interventional studies assessing efficacy of curcuma was performed, resulting in 8 clinical trials. Studies have investigated the effect of curcuma on pain, stiffness, and functionality in patients with knee osteoarthritis. Curcuma-containing products consistently demonstrated statistically significant improvement in osteoarthritis-related endpoints compared with placebo, with one exception. When compared with active control, curcuma-containing products were similar to nonsteroidal anti-inflammatory drugs, and potentially to glucosamine. While statistical significant differences in outcomes were reported in a majority of studies, the small magnitude of effect and presence of major study limitations hinder application of these results. Further rigorous studies are needed prior to recommending curcuma as an effective alternative therapy for knee osteoarthritis. © The Author(s) 2016.

Effectiveness and implementation of an obesity prevention intervention: the HeLP-her Rural cluster randomised controlled trial.

PubMed

Lombard, Catherine B; Harrison, Cheryce L; Kozica, Samantha L; Zoungas, Sophia; Keating, Catherine; Teede, Helena J

2014-06-16

To impact on the obesity epidemic, interventions that prevent weight gain across populations are urgently needed. However, even the most efficacious interventions will have little impact on obesity prevention unless they are successfully implemented in diverse populations and settings. Implementation research takes isolated efficacy studies into practice and policy and is particularly important in obesity prevention where there is an urgent need to accelerate the evidence to practice cycle. Despite the recognised need, few obesity prevention interventions have been implemented in real life settings and to our knowledge rarely target rural communities. Here we describe the rationale, design and implementation of a Healthy Lifestyle Program for women living in small rural communities (HeLP-her Rural). The primary goal of HeLP-her Rural is to prevent weight gain using a low intensity, self-management intervention. Six hundred women from 42 small rural communities in Australia will be randomised as clusters (n-21 control towns and n = 21 intervention towns). A pragmatic randomised controlled trial methodology will test efficacy and a comprehensive mixed methods community evaluation and cost analysis will inform effectiveness and implementation of this novel prevention program. Implementing population interventions to prevent obesity is complex, costly and challenging. To address these barriers, evidence based interventions need to move beyond isolated efficacy trials and report outcomes related to effectiveness and implementation. Large pragmatic trials provide an opportunity to inform both effectiveness and implementation leading to potential for greater impact at the population level. Pragmatic trials should incorporate both effectiveness and implementation outcomes and a multidimensional methodology to inform scale-up to population level. The learnings from this trial will impact on the design and implementation of population obesity prevention strategies nationally and internationally. ANZ clinical trial registry ACTRN12612000115831. Date of registration 24/01/2012.

Evidence for efficacy of acute treatment of episodic tension-type headache: methodological critique of randomised trials for oral treatments.

PubMed

Moore, R Andrew; Derry, Sheena; Wiffen, Philip J; Straube, Sebastian; Bendtsen, Lars

2014-11-01

The International Headache Society (IHS) provides guidance on the conduct of trials for acute treatment of episodic tension-type headache (TTH), a common disorder with considerable disability. Electronic and other searches identified randomised, double-blind trials of oral drugs treating episodic TTH with moderate or severe pain at baseline, or that tested drugs at first pain onset. The aims were to review methods, quality, and outcomes reported (in particular the IHS-recommended primary efficacy parameter pain-free after 2 hours), and to assess efficacy by meta-analysis. We identified 58 reports: 55 from previous reviews and searches, 2 unpublished reports, and 1 clinical trial report with results. We included 40 reports of 55 randomised trials involving 12,143 patients. Reporting quality was generally good, with potential risk of bias from incomplete outcome reporting and small size; the 23 largest trials involved 82% of patients. Few trials reported IHS outcomes. The number needed to treat values for being pain-free at 2 hours compared with placebo were 8.7 (95% confidence interval [CI] 6.2 to 15) for paracetamol 1000 mg, 8.9 (95% CI 5.9 to 18) for ibuprofen 400mg, and 9.8 (95% CI 5.1 to 146) for ketoprofen 25mg. Lower (better) number needed to treat values were calculated for outcomes of mild or no pain at 2 hours, and patient global assessment. These were similar to values for these drugs in migraine. No other drugs had evaluable results for these patient-centred outcomes. There was no evidence that any one outcome was better than others. The evidence available for treatment efficacy is small in comparison to the size of the clinical problem. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Vaxchora: A Single-Dose Oral Cholera Vaccine.

PubMed

Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

2017-07-01

To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

PubMed Central

2012-01-01

Background Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2–3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. Methods/Design Term newborns (gestational age ≥ 36 weeks and birth weight ≥ 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests. Discussion This pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns. Trial registration Current Controlled Trials ISRCTN62175998; ClinicalTrials.gov Identifier NCT01241019; EudraCT Number 2010-018627-25 PMID:22950861

A weight loss intervention using a commercial mobile application in Latino Americans-Adelgaza Trial.

PubMed

Fukuoka, Yoshimi; Vittinghoff, Eric; Hooper, Julie

2018-02-21

More than half of Latino adults living in the USA are expected to develop type 2 diabetes in their lifetime. Despite the growing interest in smartphone use for weight loss and diabetes prevention, relatively few clinical trials have evaluated the efficacy of mobile app-based interventions in Latino populations. The aim of this study was to evaluate the potential efficacy of an in-person weight loss intervention in conjunction with a commercially available Fitbit app in a Latino sample at risk for type 2 diabetes and explore significant predictors associated with weight loss. After the run-in period, 54 self-identified Latinos with body mass index (BMI) > 24.9 kg/m2 were enrolled in an 8-week uncontrolled pilot study, and received a Fitbit Zip, its app, and two in-person weight loss sessions adapted from the Diabetes Prevention Program. Mean age was 45.3 (SD ± 10.8) years, 61.1% were born in the USA, and mean BMI was 31.4 (SD ± 4.1) kg/m2. Participants lost an average of 3.3 (SD ± 3.4) % of their body weight (p < .0005). We also observed statistically significant reductions in hip and waist circumferences, and systolic and diastolic blood pressure (p < .001). After controlling for demographic factors, use of the mobile app weight diary at least twice a week (p = .01) and change in the International Physical Activity Questionnaire score (p = .03) were associated with change in percent body weight. The intervention showed the potential efficacy of this intervention, which should be formally evaluated in a randomized controlled trial.

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

PubMed Central

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

2015-01-01

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

Participation of Women and Sex Analyses in Late-Phase Clinical Trials of New Molecular Entity Drugs and Biologics Approved by the FDA in 2007–2009

PubMed Central

Poon, Rita; Khanijow, Keshav; Umarjee, Sphoorti; Yu, Monica; Zhang, Lei; Parekh, Ameeta

2013-01-01

Abstract Background Biological sex differences may contribute to differential treatment outcomes for therapeutic products. This study tracks women's participation in late-phase clinical trials (LPCTs), where efficacy and safety of drugs and biologics are evaluated, of new molecular entity (NME) drugs and biologics approved by the U.S. Food and Drug Administration (FDA) in 2007–2009. Furthermore, presentations of sex-based analyses were assessed from the FDA reviews. Methods New drug applications (NDAs) and biologics license applications (BLAs) were accessed from the U.S. FDA database and evaluated for women's participation in LPCTs. Sex-based analyses for efficacy and safety contained in FDA reviews were surveyed. Ratios for women's LPCT participation (PROPORTION OF STUDY SUBJECTS) to their proportion in the disease population were calculated for each approved therapeutic product and grouped into therapeutic categories. Results Sex-specific (n=5) and pediatric (n=3) drug applications were excluded. Women's participation in LPCTs was 39%, 48%, and 42% in NDAs (n=50) and 49%, 62%, and 58% in BLAs (n=11) for 2007, 2008, and 2009, respectively. Sixty-four percent of NDAs and 91% of BLAs had participation to proportion ratios of ≥0.80. Seventy-four percent of NDA reviews and 64% of BLA reviews included safety and efficacy sex analysis. Ninety-six percent of NDA reviews and 100% of BLA reviews included efficacy sex analysis. Conclusion Women's participation in LPCTs averaged 43% for NDAs and 57% for BLAs in 2007–2009 and varied widely by indication. As a comparison, the 2001 U.S. Government Accountability Office (GAO) reported 52% of women's participation for drug clinical trials in1998–2000 and an FDA study reported 45% for BLAs approved from 1995 to 1999. This study showed that sex-analysis of both safety and efficacy in NDA has increased to 74% since the GAO report of 72%, while those for BLAs increased to 64% from 37% reported for therapeutic biologics approved in 1995–1999. Knowledge of disease prevalence and participation in clinical trials provides an understanding of recruitment and retention patterns of patients in these trials. PMID:23768021

Stem cells in clinical trials for treatment of retinal degeneration.

PubMed

Klassen, Henry

2016-01-01

After decades of basic science research involving the testing of regenerative strategies in animal models of retinal degenerative diseases, a number of clinical trials are now underway, with additional trials set to begin shortly. These efforts will evaluate the safety and preliminary efficacy of cell-based products in the eyes of patients with a number of retinal conditions, notably including age-related macular degeneration, retinitis pigmentosa and Stargardt's disease. This review considers the scientific work and early trials with fetal cells and tissues that set the stage for the current clinical investigatory work, as well the trials themselves, specifically those either now completed, underway or close to initiation. The cells of interest include retinal pigment epithelial cells derived from embryonic stem or induced pluripotent stem cells, undifferentiated neural or retinal progenitors or cells from the vascular/bone marrow compartment or umbilical cord tissue. Degenerative diseases of the retina represent a popular target for emerging cell-based therapeutics and initial data from early stage clinical trials suggest that short-term safety objectives can be met in at least some cases. The question of efficacy will require additional time and testing to be adequately resolved.

Efficacy of Standardized Extract of Bacopa monnieri (Bacognize®) on Cognitive Functions of Medical Students: A Six-Week, Randomized Placebo-Controlled Trial

PubMed Central

Abichandani, L. G.; Thawani, Vijay; Gharpure, K. J.; Naidu, M. U. R.; Venkat Ramana, G.

2016-01-01

Rationale. Bacopa monnieri, popularly known as Brahmi, has been traditionally used in Ayurveda since ages for its memory enhancing properties. However, data on placebo-controlled trial of Bacopa monnieri on intellectual sample is scarce. Hence this study was planned to evaluate the effect of Bacopa monnieri on memory of medical students for six weeks. Objective. To evaluate the efficacy of Bacopa monnieri on memory of medical students with six weeks' administration. Method and Material. This was a randomized double blind placebo-controlled noncrossover, parallel trial. Sixty medical students of either gender from second year of medical school, third term, regular batch, were enrolled from Government Medical College, Nagpur, India. Baseline biochemical and memory tests were done. The participants were randomly divided in two groups to receive either 150 mg of standardized extract of Bacopa monnieri (Bacognize) or matching placebo twice daily for six weeks. All baseline investigations were repeated at the end of the trial. Students were followed up for 15 days after the intervention. Results. Statistically significant improvement was seen in the tests relating to the cognitive functions with use of Bacopa monnieri. Blood biochemistry also showed a significant increase in serum calcium levels (still within normal range). PMID:27803728

Learning a novel phonological contrast depends on interactions between individual differences and training paradigm design

PubMed Central

Perrachione, Tyler K.; Lee, Jiyeon; Ha, Louisa Y. Y.; Wong, Patrick C. M.

2011-01-01

Studies evaluating phonological contrast learning typically investigate either the predictiveness of specific pretraining aptitude measures or the efficacy of different instructional paradigms. However, little research considers how these factors interact—whether different students learn better from different types of instruction—and what the psychological basis for any interaction might be. The present study demonstrates that successfully learning a foreign-language phonological contrast for pitch depends on an interaction between individual differences in perceptual abilities and the design of the training paradigm. Training from stimuli with high acoustic-phonetic variability is generally thought to improve learning; however, we found high-variability training enhanced learning only for individuals with strong perceptual abilities. Learners with weaker perceptual abilities were actually impaired by high-variability training relative to a low-variability condition. A second experiment assessing variations on the high-variability training design determined that the property of this learning environment most detrimental to perceptually weak learners is the amount of trial-by-trial variability. Learners’ perceptual limitations can thus override the benefits of high-variability training where trial-by-trial variability in other irrelevant acoustic-phonetic features obfuscates access to the target feature. These results demonstrate the importance of considering individual differences in pretraining aptitudes when evaluating the efficacy of any speech training paradigm. PMID:21786912

Web-based rehabilitation interventions for people with rheumatoid arthritis: A systematic review.

PubMed

Srikesavan, Cynthia; Bryer, Catherine; Ali, Usama; Williamson, Esther

2018-01-01

Background Rehabilitation approaches for people with rheumatoid arthritis include joint protection, exercises and self-management strategies. Health interventions delivered via the web have the potential to improve access to health services overcoming time constraints, physical limitations, and socioeconomic and geographic barriers. The objective of this review is to determine the effects of web-based rehabilitation interventions in adults with rheumatoid arthritis. Methods Randomised controlled trials that compared web-based rehabilitation interventions with usual care, waiting list, no treatment or another web-based intervention in adults with rheumatoid arthritis were included. The outcomes were pain, function, quality of life, self-efficacy, rheumatoid arthritis knowledge, physical activity and adverse effects. Methodological quality was assessed using the Cochrane Risk of Bias tool and quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation approach. Results Six source documents from four trials ( n = 567) focusing on self-management, health information or physical activity were identified. The effects of web-based rehabilitation interventions on pain, function, quality of life, self-efficacy, rheumatoid arthritis knowledge and physical activity are uncertain because of the very low quality of evidence mostly from small single trials. Adverse effects were not reported. Conclusion Large, well-designed trials are needed to evaluate the clinical and cost-effectiveness of web-based rehabilitation interventions in rheumatoid arthritis.

Hydrocortisone concentration influences time to clinically significant healing of acute inflammation of the ocular surface and adnexa - results from a double-blind randomized controlled trial.

PubMed

Sergiyenko, Nikolay; Sukhina, Ludmila; Bezdetko, Pavel; Kovalenko, Yuriy; Nikitin, Nikolai; Merzbacher, Matthias; Gross, Dorothea; Kohnen, Ralf

2014-05-10

The efficacy of topical ophthalmic corticosteroids depends upon small modifications in preparations, such as drug concentration.The aim of this study was to confirm that hydrocortisone acetate (HC-ac) ophthalmic ointments of 2.5% and 1% are more effective than a 0.5% eye ointment. In this randomized, double-blind, placebo-controlled, parallel-group clinical study, the change of signs and symptoms of acute inflammation of the ocular surface and adnexa was evaluated in 411 subjects. Median time to clinically relevant response as estimated by 50% reduction in clinical signs and symptoms (CSS) total score over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h) and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001 for both dosages]. All trial medications were safe and well tolerated. Hydrocortisone acetate 2.5% and Hydrocortisone acetate 1% eye ointments are efficacious and safe treatments for acute inflammations of the ocular surface or adnexa, and showed significantly better efficacy than a control group treated with Hydrocortisone acetate 0.5% therapy. Current Controlled Trials ISRCTN15464650.

Efficacy of Acupuncture for Bell’s Palsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Li, Pingping; Qiu, Tangmeng; Qin, Chao

2015-01-01

Acupuncture has emerged as an alternative therapy for Bell’s palsy in both adults and children. However, the use of acupuncture is controversial. We conducted a systematic review and meta-analysis to assess the efficacy of acupuncture for Bell’s palsy. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, irrespective of any language restrictions. Randomized controlled trials comparing acupuncture with other therapies for Bell’s palsy in adults or children were included. Fourteen randomized controlled trials involving 1541 individuals were included in this meta-analysis. Significant association was observed in acupuncture with a higher effective response rate for Bell’s palsy (relative risk, 1.14; 95% confidence interval, 1.04–1.25; P = 0.005) but there was a heterogeneity among the studies (I 2 = 87%). An assessment of the included studies revealed a high risk of bias in methodological quality. An evaluation of the incidence of complications was not available, owing to incomplete data. Acupuncture seems to be an effective therapy for Bell’s palsy, but there was insufficient evidence to support the efficacy and safety of acupuncture. However, the results should be interpreted cautiously, because of the poor quality and heterogeneity of the included studies. PMID:25974022

OHI--Randomized Control Trial to Evaluate Efficacy, Acceptability, and Perception of Benefit of an Innovative Custom AFO

ClinicalTrials.gov

2018-05-25

Accidental Falls; Fall Due to Loss of Equilibrium; High Risk of Falls Due to Mobility Limitation; Diabetes; Arthritis; Cancer; Peripheral Arterial Disease; Parkinson's Disease; End Stage Renal Failure on Dialysis

Manual-guided psychosocial treatment. A new virtual requirement for pharmacotherapy trials?

PubMed

Carroll, K M

1997-10-01

The conduct of randomized clinical trials to evaluate the efficacy of pharmacotherapies for mental disorders is guided by research standards (at a high level of rigor) that govern most design elements, including randomization of subjects, use of placebo controls, formulation and dosage of the therapeutic agent, and monitoring of serum levels. In contrast, no such widely accepted guidelines are recognized for standardization of an essential, if unacknowledged, element of all such studies: the concomitant provision of at least a minimal form of psychosocial treatment. Standardized provision of psychosocial treatments in pharmacotherapy trials will foster replicability of findings and address several common problems (e.g., attrition, medication noncompliance, reduction of error variance, and ethical issues associated with placebo controls). Careful selection and standardization of the psychosocial context in which medications are delivered will improve the validity, precision, and power of pharmacotherapy efficacy research, and should be considered a virtual requirement in research design.

Is there a role for e-cigarettes in smoking cessation?

PubMed

Leduc, Charlotte; Quoix, Elisabeth

2016-04-01

The use of e-cigarettes has dramatically increased over the past few years and their role in smoking cessation remains controversial. Several clinical studies have evaluated their efficacy in smoking cessation but most of them are prospective cohort studies. Only two randomized, controlled trials have compared e-cigarettes versus placebo or patches. A meta-analysis of these two randomized, controlled trials has been performed. Nicotine-containing e-cigarettes appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo. However, these results are rated 'low' by GRADE standards. Many cohort studies have been conducted, with contradictory results. For some, e-cigarettes could increase the risk of nonsmokers developing nicotine dependence and of current smokers maintaining their dependence. The debate remains open and more randomized trials are needed with long-term data about the efficacy and safety of e-cigarettes. © The Author(s), 2015.

Implementation and value of using a split-plot reader design in a study of digital breast tomosynthesis in a breast cancer assessment clinic

NASA Astrophysics Data System (ADS)

Mall, Suneeta; Brennan, Patrick C.; Mello-Thoms, Claudia

2015-03-01

The rapid evolution in medical imaging has led to an increased number of recurrent trials, primarily to ensure that the efficacy of new imaging techniques is known. The cost associated with time and resources in conducting such trials is usually high. The recruitment of participants, in a medium to large reader study, is often very challenging as the demanding number of cases discourages involvement with the trial. We aim to evaluate the efficacy of Digital Breast Tomosynthesis (DBT) in a recall assessment clinic in Australia in a prospective multi-reader-multi-case (MRMC) trial. Conducting such a study with the more commonly used fully crossed MRMC study design would require more cases and more cases read per reader, which was not viable in our setting. With an aim to perform a cost effective yet statistically efficient clinical trial, we evaluated alternative study designs, particularly the alternative split-plot MRMC study design and compared and contrasted it with more commonly used fully crossed MRMC study design. Our results suggest that `split-plot', an alternative MRMC study design, could be very beneficial for medium to large clinical trials and the cost associated with conducting such trials can be greatly reduced without adversely effecting the variance of the study. We have also noted an inverse dependency between number of required readers and cases to achieve a target variance. This suggests that split-plot could also be very beneficial for studies that focus on cases that are hard to procure or readers that are hard to recruit. We believe that our results may be relevant to other researchers seeking to design a medium to large clinical trials.

Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials.

PubMed

Baracat, Felipe; Moura, Eduardo; Bernardo, Wanderley; Pu, Leonardo Zorron; Mendonça, Ernesto; Moura, Diogo; Baracat, Renato; Ide, Edson

2016-06-01

Peptic ulcer represents the most common cause of upper gastrointestinal bleeding. Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this review is to compare the different modalities of endoscopic therapy. Studies were identified by searching electronic databases MEDLINE, Embase, Cochrane, LILACS, DARE, and CINAHL. We selected randomized clinical trials that assessed contemporary endoscopic hemostatic techniques. The outcomes evaluated were: initial hemostasis, rebleeding rate, need for surgery, and mortality. The possibility of publication bias was evaluated by funnel plots. An additional analysis was made, including only the higher-quality trials. Twenty-eight trials involving 2988 patients were evaluated. Injection therapy alone was inferior to injection therapy with hemoclip and with thermal coagulation when evaluating rebleeding and the need for emergency surgery. Hemoclip was superior to injection therapy in terms of rebleeding; there were no statistically significant differences between hemoclip alone and hemoclip with injection therapy. There was considerable heterogeneity in the comparisons between hemoclip and thermal coagulation. There were no statistically significant differences between thermal coagulation and injection therapy, though their combination was superior, in terms of rebleeding, to thermal coagulation alone. Injection therapy should not be used alone. Hemoclip is superior to injection therapy, and combining hemoclip with an injectate does not improve hemostatic efficacy above hemoclip alone. Thermal coagulation has similar efficacy as injection therapy; combining these appears to be superior to thermal coagulation alone. Therefore, we recommend the application of hemoclips or the combined use of injection therapy with thermal coagulation for the treatment of peptic ulcer bleeding.

Differential Efficacy of Nicotine Replacement Among Overweight and Obese Women Smokers.

PubMed

Strong, David R; David, Sean P; Johnstone, Elaine C; Aveyard, Paul; Murphy, Michael F; Munafò, Marcus R

2015-07-01

Rates of obesity are higher among more dependent smokers and 37%-65% of smokers seeking cessation treatment are overweight or obese. Overweight or obese smokers may possess metabolic and neurobiological features that contribute to difficulty achieving cessation using front-line nicotine replacement products. Attention to factors that facilitate effective cessation treatment in this vulnerable population is needed to significantly reduce mortality risk among overweight and obese smokers. This secondary analysis of 2 large trials of transdermal nicotine replacement in general medical practices evaluated the hypothesis that higher body mass index (BMI) would moderate the efficacy of the nicotine patch. We examined the potential for gender to further moderate the relationship between BMI and treatment efficacy. In the placebo controlled trial (N = 1,621), 21-mg patch was no more effective than placebo for assisting biochemically verified point prevalence abstinence up to 1 year after quitting for women with higher BMI, but appeared to be effective for men at normal or high BMI (gender × BMI beta = -0.22, p = .004). We did not find differential long-term cessation outcomes among male or female smokers in the 15-mg patch trial (n = 705). However, we observed significantly higher rates of early lapse among women with higher BMI treated with nicotine patch across both trials. These results suggest that increased BMI may affect the efficacy of nicotine patch on reducing risk of early lapse in women. Additional research is needed to explore mechanisms of risk for decreased efficacy of this commonly used cessation aid. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Safety and efficacy of autologous cell therapy in critical limb ischemia: a systematic review.

PubMed

Benoit, Eric; O'Donnell, Thomas F; Patel, Amit N

2013-01-01

Researchers have accumulated a decade of experience with autologous cell therapy in the treatment of critical limb ischemia (CLI). We conducted a systematic review of clinical trials in the literature to determine the safety and efficacy of cell therapy in CLI. We searched the literature for clinical trials of autologous cell therapy in CLI, including observational series of five or more patients to accrue a large pool of patients for safety analysis. Safety analysis included evaluation of death, cancer, unregulated angiogenesis, and procedural adverse events such as bleeding. Efficacy analysis included the clinical endpoints amputation and death as well as functional and surrogate endpoints. We identified 45 clinical trials, including seven RCTs, and 1,272 patients who received cell therapy. The overall adverse event rate was low (4.2%). Cell therapy patients did not have a higher mortality rate than control patients and demonstrated no increase in cancer incidence when analyzed against population rates. With regard to efficacy, cell therapy patients had a significantly lower amputation rate than control patients (OR 0.36, p = 0.0004). Cell therapy also demonstrated efficacy in a variety of functional and surrogate outcomes. Clinical trials differed in the proportion of patients with risk factors for clinical outcomes, and these influenced rates of amputation and death. Cell therapy presents a favorable safety profile with a low adverse event rate and no increase in severe events such as mortality and cancer and treatment with cell therapy decreases the risk of amputation. Cell therapy has a positive benefit-to-risk ratio in CLI and may be a valuable treatment option, particularly for those challenging patients who cannot undergo arterial reconstruction.

Efficacy of the trial-based thought record, a new cognitive therapy strategy designed to change core beliefs, in social phobia.

PubMed

de Oliveira, I R; Powell, V B; Wenzel, A; Caldas, M; Seixas, C; Almeida, C; Bonfim, T; Grangeon, M C; Castro, M; Galvão, A; de Oliveira Moraes, R; Sudak, D

2012-06-01

Social anxiety disorder (SAD) often follows a chronic course and is associated with substantial impairment in functioning. Although results from clinical trials clearly establish evidence for efficacy of cognitive behavioural therapy in treating this disorder, up to 50% of patients with SAD show little or no improvement. Thus, new approaches that have promised in improving the efficacy of treatment for SAD are needed. One such approach is the trial-based thought record (TBTR), which targets the restructuring of patients' core beliefs. To determine whether patients receiving TBTR would report fewer symptoms of social anxiety and general psychiatric distress following treatment, relative to conventional cognitive therapy (CCT). A two-arm randomized trial comparing TBTR (n = 17) with a set of CCT techniques (n = 19), which included the standard seven-column dysfunctional thought record and the positive data log in SAD patients according to DSM-IV. Scores on many outcome measures decreased significantly across the course of treatment in both groups (P < 0·001), including the Liebowitz Social Anxiety Scale, Fear of Negative Evaluation Scale (FNE), Social Avoidance and Distress Scale (SADS), Beck Anxiety Inventory, and Clinical Global Impression - Improvement. In addition, a one-way ancova, taking baseline values as covariates, showed that TBTR was significantly more efficacious than CCT in reducing the scores of FNE (P = 0·01 at mid-treatment and P = 0·004 at post-treatment), and SADS (P = 0·03 at post-treatment). This study provides preliminary evidence that TBTR is at least as efficacious as CCT in reducing symptoms of SAD, pointing to the need for additional studies of TBTR in SAD and other psychiatric disorders. © 2011 Blackwell Publishing Ltd.

A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults.

PubMed

Gray, Kevin M; Sonne, Susan C; McClure, Erin A; Ghitza, Udi E; Matthews, Abigail G; McRae-Clark, Aimee L; Carroll, Kathleen M; Potter, Jennifer S; Wiest, Katharina; Mooney, Larissa J; Hasson, Albert; Walsh, Sharon L; Lofwall, Michelle R; Babalonis, Shanna; Lindblad, Robert W; Sparenborg, Steven; Wahle, Aimee; King, Jacqueline S; Baker, Nathaniel L; Tomko, Rachel L; Haynes, Louise F; Vandrey, Ryan G; Levin, Frances R

2017-08-01

Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18-50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio=1.00, 95% confidence interval 0.63-1.59, p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. In contrast with prior findings in adolescents, there is no evidence that NAC 1200mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of safety and efficacy of 980-nm diode laser-assisted lipolysis versus traditional liposuction for submental rejuvenation: A randomized clinical trial.

PubMed

Valizadeh, Neda; Jalaly, Niloofar Y; Zarghampour, Manijeh; Barikbin, Behrooz; Haghighatkhah, Hamid Reza

2016-01-01

Submental fat accumulation and skin laxity is a frequent concern of cosmetic patients. The aim of this randomized prospective controlled clinical trial was to compare the efficacy and safety of laser-assisted lipolysis and liposuction in the submental rejuvenation. Thirty-six female adults were enrolled in this clinical trial and were categorized into two groups: group 1 underwent 980-nm diode laser with the power of 6-8 W and group 2 underwent traditional liposuction. Patients were evaluated with ultrasonography 2 weeks and 2 months after the procedures. Ultrasonographic evaluation reported the significant reduction of fat thickness in each group compared with the baseline (p value < 0.001). At the 2 weeks and 2 months follow-up visit, fat thickness reduction was significantly higher in the lipolysis group (p value < 0.05). Overall patients' satisfaction in lipolysis group was higher than liposuction with 11 (61%) of lipolysis patients being very satisfied in contrast to 10 (55.5%) of liposuction patients reporting "dissatisfied or neutral" results. Laser-assisted lipolysis using 980-nm diode is approved to be safe and effective for skin tightening and rejuvenation of the submental area and seems to be a better option than traditional techniques for treatment of this cosmetic problem.

Efficacy of a multifaceted podiatry intervention to improve balance and prevent falls in older people: study protocol for a randomised trial.

PubMed

Spink, Martin J; Menz, Hylton B; Lord, Stephen R

2008-11-25

Falls in older people are a major public health problem, with at least one in three people aged over 65 years falling each year. There is increasing evidence that foot problems and inappropriate footwear increase the risk of falls, however no studies have been undertaken to determine whether modifying these risk factors decreases the risk of falling. This article describes the design of a randomised trial to evaluate the efficacy of a multifaceted podiatry intervention to reduce foot pain, improve balance, and reduce falls in older people. Three hundred community-dwelling men and women aged 65 years and over with current foot pain and an increased risk of falling will be randomly allocated to a control or intervention group. The "usual cae" control group will receive routine podiatry (i.e. nail care and callus debridement). The intervention group will receive usual care plus a multifaceted podiatry intervention consisting of: (i) prefabricated insoles customised to accommodate plantar lesions; (ii) footwear advice and assistance with the purchase of new footwear if current footwear is inappropriate; (iii) a home-based exercise program to strengthen foot and ankle muscles; and (iv) a falls prevention education booklet. Primary outcome measures will be the number of fallers, number of multiple fallers and the falls rate recorded by a falls diary over a 12 month period. Secondary outcome measures assessed six months after baseline will include the Medical Outcomes Study Short Form 12 (SF-12), the Manchester Foot Pain and Disability Index, the Falls Efficacy Scale International, and a series of balance and functional tests. Data will be analysed using the intention to treat principle. This study is the first randomised trial to evaluate the efficacy of podiatry in improving balance and preventing falls. The trial has been pragmatically designed to ensure that the findings can be generalised to clinical practice. If found to be effective, the multifaceted podiatry intervention will be a unique addition to common falls prevention strategies already in use. Australian New Zealand Clinical Trials Registry: ACTRN12608000065392.

Smoking cessation and reduction in schizophrenia (SCARIS) with e-cigarette: study protocol for a randomized control trial.

PubMed

Caponnetto, Pasquale; Polosa, Riccardo; Auditore, Roberta; Minutolo, Giuseppe; Signorelli, Maria; Maglia, Marilena; Alamo, Angela; Palermo, Filippo; Aguglia, Eugenio

2014-03-22

It is well established in studies across several countries that tobacco smoking is more prevalent among schizophrenic patients than the general population. Electronic cigarettes are becoming increasingly popular with smokers worldwide. To date there are no large randomized trials of electronic cigarettes in schizophrenic smokers. A well-designed trial is needed to compare efficacy and safety of these products in this special population. We have designed a randomized controlled trial investigating the efficacy and safety of electronic cigarette. The trial will take the form of a prospective 12-month randomized clinical study to evaluate smoking reduction, smoking abstinence and adverse events in schizophrenic smokers not intending to quit. We will also monitor quality of life, neurocognitive functioning and measure participants' perception and satisfaction of the product. A ≥50% reduction in the number of cigarettes/day from baseline, will be calculated at each study visit ("reducers"). Abstinence from smoking will be calculated at each study visit ("quitters"). Smokers who leave the study protocol before its completion and will carry out the Early Termination Visit or who will not satisfy the criteria of "reducers" and "quitters" will be defined "non responders". The differences of continuous variables between the three groups will be evaluated with the Kruskal-Wallis Test, followed by the Dunn multiple comparison test. The differences between the three groups for normally distributed data will be evaluated with ANOVA test one way, followed by the Newman-Keuls multiple comparison test. The normality of the distribution will be evaluated with the Kolmogorov-Smirnov test. Any correlations between the variables under evaluation will be assessed by Spearman r correlation. To compare qualitative data will be used the Chi-square test. The main strengths of the SCARIS study are the following: it's the first large RCT on schizophrenic patient, involving in and outpatient, evaluating the effect of a three-arm study design, and a long term of follow-up (52-weeks).The goal is to propose an effective intervention to reduce the risk of tobacco smoking, as a complementary tool to treat tobacco addiction in schizophrenia. ClinicalTrials.gov, NCT01979796.

A Controlled Pilot Trial of PainTracker Self-Manager, a Web-Based Platform Combined With Patient Coaching, to Support Patients' Self-Management of Chronic Pain.

PubMed

Sullivan, Mark; Langford, Dale J; Davies, Pamela Stitzlein; Tran, Christine; Vilardaga, Roger; Cheung, Gifford; Yoo, Daisy; McReynolds, Justin; Lober, William B; Tauben, David; Vowles, Kevin E

2018-03-29

The objective of this study was to develop and pilot test a chronic pain empowerment and self-management platform, derived from acceptance and commitment therapy, in a pain specialty setting. A controlled, sequential, nonrandomized study design was used to accommodate intervention development and to test the efficacy of the PainTracker Self-Manager (PTSM) intervention (Web-based educational modules and outcome tracking combined with tailored patient coaching sessions and provider guidance). Generalized estimating equations evaluated changes over time (baseline, 3 months, 6 months) in pain self-efficacy (primary outcome), chronic pain acceptance (activity engagement and pain willingness), perceived efficacy in patient-provider interactions, pain intensity and interference, and overall satisfaction with pain treatment (secondary outcomes) between intervention (n = 48) and usual care control groups (n = 51). The full study sample (N = 99) showed greater improvements over time (significant Group × Time interactions) in pain self-efficacy and satisfaction with pain treatment. Among study completers (n = 82), greater improvement in activity engagement as well as pain intensity and interference were also observed. These preliminary findings support the efficacy of the PTSM intervention in a pain specialty setting. Further research is needed to refine and expand the PTSM intervention and to test it in a randomized trial in primary care settings. We developed a Web-based patient empowerment platform that combined acceptance and commitment therapy-based educational modules and tailored coaching sessions with longitudinal tracking of treatments and patient-reported outcomes, named PTSM. Pilot controlled trial results provide preliminary support for its efficacy in improving pain self-efficacy, activity engagement, pain intensity and interference, and satisfaction with pain treatment. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Self-stigma and empowerment in combined-CMHA and consumer-run services: two controlled trials.

PubMed

Segal, Steven P; Silverman, Carol J; Temkin, Tanya L

2013-10-01

Self-help agencies (SHAs) are consumer-operated service organizations managed as participatory democracies involving members in all management tasks. Hierarchically organized board- and staff-run consumer-operated service programs (BSR-COSPs) are consumer managed, but they afford members less decision-making power. This study considered the relative effectiveness of SHAs and BSR-COSPs working jointly with community mental health agencies (CMHAs) and the role of organizational empowerment in reducing self-stigma. Clients seeking CMHA services were assigned in separate randomized controlled trials to a trial of combined SHA and CMHA services versus regular CMHA services (N=505) or to a trial of combined BSR-COSP and CMHA services versus regular CMHA services (N=139). Self-stigma, organizational empowerment, and self-efficacy were assessed at baseline and eight months with the Attitudes Toward Persons With Mental Illness Scale, the Organizationally Mediated Empowerment Scale, and the Self-Efficacy Scale. Outcomes were evaluated with fully recursive path analysis models. SHA-CMHA participants experienced greater positive change in self-stigma than CMHA-only participants, a result attributable to participation in the combined condition (b=1.20, p=.016) and increased organizational empowerment (b=.27, p=.003). BSR-COSP-CMHA participants experienced greater negative change in self-stigma than CMHA-only participants, a result attributable to participation in the combined service (b=-4.73, p=.031). In the SHA-CMHA trial, participants showed positive change in self-efficacy, whereas the change among BSR-COSP-CMHA participants was negative. Differential organizational empowerment efforts in the SHA and BSR-COSP appeared to account for the differing outcomes. Members experienced reduced self-stigma and increases in self-efficacy when they were engaged in responsible roles.

A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

PubMed

Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

2016-08-17

This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis.

PubMed

Zhu, Mingming; Xu, Xitao; Nie, Fang; Tong, Jinlu; Xiao, Shudong; Ran, Zhihua

2011-08-01

The use of selective leukocytapheresis for the treatment of ulcerative colitis (UC) has been evaluated in several open and controlled trials, with varying outcomes. A meta-analysis was performed to better assess the efficacy and safety of selective leukocytapheresis as supplemental therapy compared with conventional pharmacotherapy in patients with UC. All randomized trials comparing selective leukocytapheresis supplementation with conventional pharmacotherapy were included from electronic databases and reference lists. A meta-analysis that pooled the outcome effects of leukocytapheresis and pharmacotherapy was performed. A fixed effect model or random effect model was selected depending on the heterogeneity test of the trials. Nine randomized controlled trials met the inclusion criteria contributing a total of 686 participants. Compared with conventional pharmacotherapy, leukocytapheresis supplementation presented a significant benefit in promoting a response rate (OR, 2.88, 95% CI: 1.60-5.18) and remission rate (OR, 2.04; 95% CI, 1.36-3.07) together with significant higher steroid-sparing effects (OR, 10.49; 95% CI, 3.44-31.93) in patients with active moderate-to-severe UC by intention-to-treat analysis. Leukocytapheresis was more effective in maintaining clinical remission for asymptomatic UC patients than conventional therapy (OR, 8.14; 95% CI, 2.22-29.90). The incidence of mild-moderate adverse effects was much less frequent in the leukocytapheresis groups than conventional pharmacotherapy groups (OR, 0.16; 95% CI, 0.04-0.60). Few severe adverse events were observed. Current data indicate that leukocytapheresis supplementation may be more efficacious on improving response and remission rates and tapering corticosteroid dosage with excellent tolerability and safety than conventional pharmacotherapy in patients with UC. In addition, more high-quality randomized controlled trials are required to confirm the higher efficacy of leukocytapheresis in patients with UC.

Efficacy of preparation solutions and cleansing techniques on contamination of the skin in foot and ankle surgery: A systematic review and meta-analysis.

PubMed

Yammine, K; Harvey, A

2013-04-01

We report a systematic review and meta-analysis of published randomised and quasi-randomised trials evaluating the efficacy of pre-operative skin antisepsis and cleansing techniques in reducing foot and ankle skin flora. The post-preparation culture number (Post-PCN) was the primary outcome. The data were evaluated using a modified version of the Cochrane Collaboration’s tool. We identified eight trials (560 participants, 716 feet) that met the inclusion criteria. There was a significant difference in the proportions of Post-PCN between hallux nailfold (HNF) and toe web spaces (TWS) sites: 0.47 vs 0.22, respectively (95% confidence interval (CI) 0.182937 to 0.304097; p < 0.0001). Meta-analyses showed that alcoholic chlorhexidine had better efficacy than alcoholic povidone-iodine (PI) at HNF sites (risk difference 0.19 (95% CI 0.08 to 0.30); p = 0.0005); a two-step intervention using PI scrub and paint (S&P) followed by alcohol showed significantly better efficacy over PI (S&P) alone at TWS sites (risk difference 0.13 (95% CI 0.02 to 0.24); p = 0.0169); and a two-step intervention using chlorhexidine scrub followed by alcohol showed significantly better efficacy over PI (S&P) alone at the combined (HNF with TWS) sites (risk difference 0.27 (95% CI 0.13 to 0.40); p < 0.0001). No significant difference was found between cleansing techniques.

Efficacy of theory-based HIV behavioral prevention among rural-to-urban migrants in China: a randomized controlled trial.

PubMed

Li, Xiaoming; Lin, Danhua; Wang, Bo; Du, Hongfei; Tam, Cheuk Chi; Stanton, Bonita

2014-08-01

Our objective was to evaluate the efficacy of a cultural adaptation of a social cognitive theory-based HIV behavioral prevention program among young rural-to-urban migrants in China. The intervention design and assessment were guided by the Protection Motivation Theory (PMT). The intervention was evaluated through a randomized controlled trial with 6-month and 12-month follow-ups. The primary behavioral outcome was the use of condoms. Other outcome measures include HIV knowledge, condom use knowledge, HIV-related perceptions (PMT constructs), and intention to use condom. The mixed-effects regression models for condom use with regular partners indicated that overall frequency of condom use, condom use in last three sexual acts and proper condom use increased over time for the participants but the increases were significantly greater among the intervention group than the control group at 6-month and 12-month follow-ups. The mixed-effects models for HIV-related perceptions indicated that extrinsic rewards, intrinsic rewards, and response costs decreased while vulnerability, severity, response efficacy, and self-efficacy increased over time for the intervention group. The increases in HIV knowledge, condom use knowledge, and intention to use condom were also significantly greater among the intervention group than the control group. The data in the current study suggested efficacy of a social cognitive theory-based behavioral intervention in increasing condom use among young migrants in China. The intervention also increased protective perceptions and decreased risk perception posited by the theory (i.e., PMT).

Testing the effectiveness of a self-efficacy based exercise intervention for inactive people with type 2 diabetes mellitus: design of a controlled clinical trial

PubMed Central

2012-01-01

Background Sufficient exercise is important for people with Type 2 Diabetes Mellitus (T2DM), as it can prevent future health problems. Despite, it is estimated that only 30-40% of people with T2DM are sufficiently active. One of the psychosocial constructs that is believed to influence physical activity behaviour, is exercise self-efficacy. The goal of this study is to evaluate a patient-tailored exercise intervention for people with T2DM that takes exercise self-efficacy into account. Methods/Design This study is conducted as a non-randomized controlled clinical trial. Patients are eligible when they are diagnosed with T2DM, exercise less than advised in the ADA guideline of 150 min/week of moderate-intensity aerobic physical activity, have an BMI >25 and are between 18 and 80 years old. Recruitment takes place at a Primary care organization of general practitioners and practice nurses in the south of the Netherlands. Participants are allocated to three groups: An advice intervention -for participants with a high exercise self-efficacy score- in which participants receive a patient-tailored exercise intervention, an intensive intervention -for participants with a low exercise self-efficacy score- in which participants receive a patient-tailored exercise intervention accomplished by a group based intervention, and a control group in which participants receive regular Dutch diabetes care. The primary outcome measure of this study is physical activity. Secondary outcome measures are health status, (symptoms of) depression, exercise self-efficacy, Body Mass Index (BMI), blood pressure and glycemic control. Discussion We aimed to design an intervention that can be implemented in Primary care, but also to design an easy accessible program. This study is innovative as it is -to our best knowledge- the first study that takes level of exercise self-efficacy of people with T2DM into account by means of giving extra support to those with the lowest exercise self-efficacy. If the program succeeds in increasing the amount of physical activity it can be implemented in regular primary care. Trial registration Dutch Trial Register NTR2734 PMID:22559322

Is the Generally Held View That Intravenous Dihydroergotamine Is Effective in Migraine Based on Wrong "General Consensus" of One Trial? A Critical Review of the Trial and Subsequent Quotations.

PubMed

Bekan, Goran; Tfelt-Hansen, Peer

2016-10-01

The claim that parenteral dihydroergotamine (DHE) is effective in migraine is based on one randomized, placebo-controlled, crossover trial from 1986. The aim of this review was to critically evaluate the original article. It was also found to be of interest to review quotes concerning the results in the more than 100 articles subsequently referring to the article. The correctness of the stated effect of intravenous DHE in the randomized clinical trial (RCT) was first critically evaluated. Then, Google Scholar was searched for references to the article and these references were classified as to whether they judged the reported RCT as positive or negative. The design of the RCT, with a crossover within one migraine attack, only allows evaluation of the results for the first period and the effect of DHE and placebo were quite comparable. About 151 references were found for the article in Google scholar. Among the 95 articles with a judgment on the efficacy of intravenous DHE in the RCT, 90 stated that DHE was effective or likely effective whereas only 5 articles stated that DHE was ineffective. Despite a "negative" RCT, authors of subsequent articles on the efficacy of parenteral DHE overwhelmingly reported this RCT as "positive." This is probably due to the fact that the authors concluded in the abstract that DHE is effective, and to a kind of "wrong general consensus." © 2016 American Headache Society.

Evaluation of the RPi-ber late blight resistance gene for tuber resistance in the field and laboratory.

USDA-ARS?s Scientific Manuscript database

The purpose of this research was to evaluate the efficacy in tubers of a late blight resistance gene, RPi-ber, originating from Solanum berthaultii. Experiments were conducted in the field and laboratory. Inoculation of tubers in field trials occurred via sporangia produced on infections in the foli...

The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics.

PubMed

Garner, Alan A; Fearnside, Michael; Gebski, Val

2013-09-14

The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. ClinicalTrials.gov: NCT00112398.

Internet-Delivered Psychological Treatments for Mood and Anxiety Disorders: A Systematic Review of Their Efficacy, Safety, and Cost-Effectiveness

PubMed Central

Arnberg, Filip K.; Linton, Steven J.; Hultcrantz, Monica; Heintz, Emelie; Jonsson, Ulf

2014-01-01

Background Greater access to evidence-based psychological treatments is needed. This review aimed to evaluate whether internet-delivered psychological treatments for mood and anxiety disorders are efficacious, noninferior to established treatments, safe, and cost-effective for children, adolescents and adults. Methods We searched the literature for studies published until March 2013. Randomized controlled trials (RCTs) were considered for the assessment of short-term efficacy and safety and were pooled in meta-analyses. Other designs were also considered for long-term effect and cost-effectiveness. Comparisons against established treatments were evaluated for noninferiority. Two reviewers independently assessed the relevant studies for risk of bias. The quality of the evidence was graded using an international grading system. Results A total of 52 relevant RCTs were identified whereof 12 were excluded due to high risk of bias. Five cost-effectiveness studies were identified and three were excluded due to high risk of bias. The included trials mainly evaluated internet-delivered cognitive behavioral therapy (I-CBT) against a waiting list in adult volunteers and 88% were conducted in Sweden or Australia. One trial involved children. For adults, the quality of evidence was graded as moderate for the short-term efficacy of I-CBT vs. waiting list for mild/moderate depression (d = 0.83; 95% CI 0.59, 1.07) and social phobia (d = 0.85; 95% CI 0.66, 1.05), and moderate for no efficacy of internet-delivered attention bias modification vs. sham treatment for social phobia (d = −0.04; 95% CI −0.24, 0.35). The quality of evidence was graded as low/very low for other disorders, interventions, children/adolescents, noninferiority, adverse events, and cost-effectiveness. Conclusions I-CBT is a viable treatment option for adults with depression and some anxiety disorders who request this treatment modality. Important questions remain before broad implementation can be supported. Future research would benefit from prioritizing adapting treatments to children/adolescents and using noninferiority designs with established forms of treatment. PMID:24844847

Control of Frankliniella occidentalis with foliar insecticides, 2014

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate the efficacy of selected chemical insecticides against a western flower thrips Frankliniella occidentalis Pergande, in ornamental pepper under greenhouse condition. The trial was conducted at United States Horticultural Research Laboratory in Fort Pierce, ...

The efficacy-effectiveness distinction in trials of alcohol brief intervention

PubMed Central

2014-01-01

Three recent sets of null findings from trials of alcohol brief intervention (BI) have been disappointing to those who wish to see a reduction in alcohol-related harm through the widespread dissemination of BI. Saitz (7) has suggested that these null findings result from a failure to translate the effects of BI seen in efficacy trials, which are thought to contribute mainly to the beneficial effects of BI shown in meta-analyses, to effectiveness trials conducted in real-world clinical practice. The present article aims to: (i) clarify the meaning of the terms “efficacy” and “effectiveness” and other related concepts; (ii) review the method and findings on efficacy-effectiveness measurement in the 2007 Cochrane Review by Kaner and colleagues; and (iii) make suggestions for further research in this area. Conclusions are: 1) to avoid further confusion, terms such as “efficacy trial”, “effectiveness trial”, “clinical representativeness”, etc. should be clearly defined and carefully used; 2) applications of BI to novel settings should begin with foundational research and developmental studies, followed by efficacy trials, and political pressures for quick results from premature effectiveness trials should be resisted; 3) clear criteria are available in the literature to guide progress from efficacy research, through effectiveness research, to dissemination in practice; 4) to properly interpret null findings from effectiveness studies, it is necessary to ensure that interventions are delivered as intended; 5) in future meta-analyses of alcohol BI trials, more attention should be paid to the development and application of a psychometrically robust scale to measure efficacy-effectiveness or clinical representativeness; 6) the null findings under consideration cannot be firmly attributed to a failure to translate effects from efficacy trials to real-world practice, because it is possible that the majority of trials included in meta-analyses on which the evidence for the beneficial effects of alcohol BI was based tended to be effectiveness rather than efficacy trials; and 7) a hypothesis to explain the null findings in question is that they are due to lack of fidelity in the implementation of BI in large, organizationally complex, cluster randomized trials. PMID:25127717

Safety and efficacy of the predictive low glucose management system in the prevention of hypoglycaemia: protocol for randomised controlled home trial to evaluate the Suspend before low function

PubMed Central

Abraham, M B; Nicholas, J A; Ly, T T; Roby, H C; Paramalingam, N; Fairchild, J; King, B R; Ambler, G R; Cameron, F; Davis, E A; Jones, T W

2016-01-01

Introduction Innovations with sensor-augmented pump therapy (SAPT) to reduce hypoglycaemia in patients with type 1 diabetes are an ongoing area of research. The predictive low glucose management (PLGM) system incorporates continuous glucose sensor data into an algorithm and suspends basal insulin before the occurrence of hypoglycaemia. The system was evaluated in in-clinic studies, and has informed the parameters of a larger home trial to study its efficacy and safety in real life. Methods and analysis The aim of this report is to describe the study design and outcome measures for the trial. This is a 6-month, multicentre, randomised controlled home trial to test the PLGM system in children and adolescents with type 1 diabetes. The system is available in the Medtronic MiniMed 640G pump as the ‘Suspend before low’ feature. Following a run-in period, participants are randomised to either the control arm with SAPT alone or the intervention arm with SAPT and Suspend before low. The primary aim of this study is to evaluate the time spent hypoglycaemic (sensor glucose <3.5 mmol/L) with and without the system. The secondary aims are to determine the number of hypoglycaemic events, the time spent hyperglycaemic, and to evaluate safety with ketosis and changes in glycated haemoglobin. The study also aims to assess the changes in counter-regulatory hormone responses to hypoglycaemia evaluated by a hyperinsulinaemic hypoglycaemic clamp in a subgroup of patients with impaired awareness. Validated questionnaires are used to measure the fear of hypoglycaemia and the impact on the quality of life to assess burden of the disease. Ethics and dissemination Ethics committee permissions were gained from respective Institutional Review boards. The findings of the study will provide high quality evidence of the ability of the system in the prevention of hypoglycaemia in real life. Trial registration number ACTRN12614000510640, Pre-results. PMID:27084290

Effects of Gait Self-Efficacy and Lower-Extremity Physical Function on Dual-Task Performance in Older Adults

PubMed Central

Banducci, Sarah E.; Daugherty, Ana M.; Fanning, Jason; Awick, Elizabeth A.; Porter, Gwenndolyn C.; Burzynska, Agnieszka; Shen, Sa; Kramer, Arthur F.; McAuley, Edward

2017-01-01

Objectives. Despite evidence of self-efficacy and physical function's influences on functional limitations in older adults, few studies have examined relationships in the context of complex, real-world tasks. The present study tested the roles of self-efficacy and physical function in predicting older adults' street-crossing performance in single- and dual-task simulations. Methods. Lower-extremity physical function, gait self-efficacy, and street-crossing success ratio were assessed in 195 older adults (60–79 years old) at baseline of a randomized exercise trial. During the street-crossing task, participants walked on a self-propelled treadmill in a virtual reality environment. Participants crossed the street without distraction (single-task trials) and conversed on a cell phone (dual-task trials). Structural equation modeling was used to test hypothesized associations independent of demographic and clinical covariates. Results. Street-crossing performance was better on single-task trials when compared with dual-task trials. Direct effects of self-efficacy and physical function on success ratio were observed in dual-task trials only. The total effect of self-efficacy was significant in both conditions. The indirect path through physical function was evident in the dual-task condition only. Conclusion. Physical function can predict older adults' performance on high fidelity simulations of complex, real-world tasks. Perceptions of function (i.e., self-efficacy) may play an even greater role. The trial is registered with United States National Institutes of Health ClinicalTrials.gov (ID: NCT01472744; Fit & Active Seniors Trial). PMID:28255557

Achieving cannabis cessation -- evaluating N-acetylcysteine treatment (ACCENT): design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network.

PubMed

McClure, Erin A; Sonne, Susan C; Winhusen, Theresa; Carroll, Kathleen M; Ghitza, Udi E; McRae-Clark, Aimee L; Matthews, Abigail G; Sharma, Gaurav; Van Veldhuisen, Paul; Vandrey, Ryan G; Levin, Frances R; Weiss, Roger D; Lindblad, Robert; Allen, Colleen; Mooney, Larissa J; Haynes, Louise; Brigham, Gregory S; Sparenborg, Steve; Hasson, Albert L; Gray, Kevin M

2014-11-01

Despite recent advances in behavioral interventions for cannabis use disorders, effect sizes remain modest, and few individuals achieve long-term abstinence. One strategy to enhance outcomes is the addition of pharmacotherapy to complement behavioral treatment, but to date no efficacious medications targeting cannabis use disorders in adults through large, randomized controlled trials have been identified. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) is currently conducting a study to test the efficacy of N-acetylcysteine (NAC) versus placebo (PBO), added to contingency management, for cannabis cessation in adults (ages 18-50). This study was designed to replicate positive findings from a study in cannabis-dependent adolescents that found greater odds of abstinence with NAC compared to PBO. This paper describes the design and implementation of an ongoing 12-week, intent-to-treat, double-blind, randomized, placebo-controlled study with one follow-up visit four weeks post-treatment. Approximately 300 treatment-seeking cannabis-dependent adults will be randomized to NAC or PBO across six study sites in the United States. The primary objective of this 12-week study is to evaluate the efficacy of twice-daily orally-administered NAC (1200 mg) versus matched PBO, added to contingency management, on cannabis abstinence. NAC is among the first medications to demonstrate increased odds of abstinence in a randomized controlled study among cannabis users in any age group. The current study will assess the cannabis cessation efficacy of NAC combined with a behavioral intervention in adults, providing a novel and timely contribution to the evidence base for the treatment of cannabis use disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficacy and tolerability of Ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials

PubMed Central

Gauthier, Serge; Schlaefke, Sandra

2014-01-01

The objective of this systematic review was to evaluate current evidence for the efficacy of Ginkgo biloba extract EGb 761® in dementia. Seven of 15 randomized, placebocontrolled trials in patients with dementia identified by database searches met all our selection criteria and were included in the meta-analysis. In these trials, patients were treated with 120 mg or 240 mg per day of the defined extract EGb 761 or placebo. Efficacy was assessed using validated tests and rating scales for the cognitive domain, the functional domain (activities of daily living), and global assessment. Tolerability was evaluated by risk differences based on incidences of adverse events and premature discontinuation rates. Of 2,684 outpatients randomized to receive treatment for 22–26 weeks, 2,625 represented the full analysis sets (1,396 for EGb 761 and 1,229 for placebo). Standardized mean differences for change in cognition (−0.52; 95% confidence interval [CI] −0.98, −0.05; P=0.03), activities of daily living (−0.44; 95% CI −0.68, −0.19; P<0.001), and global rating (−0.52; 95% CI −0.92, −0.12; P=0.01) significantly favored EGb 761 compared with placebo. Statistically significant superiority of EGb 761 over placebo was confirmed by responder analyses as well as for patients suffering from dementia with neuropsychiatric symptoms. Treatment-associated risks in terms of relative risks of adverse events and premature withdrawal rates did not differ noticeably between the two treatment groups. In conclusion, meta-analyses confirmed the efficacy and good tolerability of Ginkgo biloba extract EGb 761 in patients with dementia. PMID:25506211

Achieving Cannabis Cessation - Evaluating N-acetylcysteine Treatment (ACCENT): Design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network

PubMed Central

McClure, Erin A.; Sonne, Susan C.; Winhusen, Theresa; Carroll, Kathleen M.; Ghitza, Udi E.; McRae-Clark, Aimee L.; Matthews, Abigail G.; Sharma, Gaurav; Van Veldhuisen, Paul; Vandrey, Ryan G.; Levin, Frances R.; Weiss, Roger D.; Lindblad, Robert; Allen, Colleen; Mooney, Larissa J.; Haynes, Louise; Brigham, Gregory S.; Sparenborg, Steve; Hasson, Albert L.; Gray, Kevin M.

2014-01-01

Despite recent advances in behavioral interventions for cannabis use disorders, effect sizes remain modest, and few individuals achieve long-term abstinence. One strategy to enhance outcomes is the addition of pharmacotherapy to complement behavioral treatment, but to date no efficacious medications targeting cannabis use disorders in adults through large, randomized controlled trials have been identified. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) is currently conducting a study to test the efficacy of N-acetylcysteine (NAC) versus placebo (PBO), added to contingency management, for cannabis cessation in adults (ages 18–50). This study was designed to replicate positive findings from a study in cannabis-dependent adolescents that found greater odds of abstinence with NAC compared to PBO. This paper describes the design and implementation of an ongoing 12-week, intent-to-treat, double-blind, randomized, placebo-controlled study with one follow-up visit four weeks post-treatment. Approximately 300 treatment-seeking cannabis-dependent adults will be randomized to NAC or PBO across six study sites in the United States. The primary objective of this 12-week study is to evaluate the efficacy of twice-daily orally-administered NAC (1200 mg) versus matched PBO, added to contingency management, on cannabis abstinence. NAC is among the first medications to demonstrate increased odds of abstinence in a randomized controlled study among cannabis users in any age group. The current study will assess the cannabis cessation efficacy of NAC combined with a behavioral intervention in adults, providing a novel and timely contribution to the evidence base for the treatment of cannabis use disorders. PMID:25179587

New oral anticoagulants in patients with cancer: current state of evidence.

PubMed

Sardar, Partha; Chatterjee, Saurav; Herzog, Eyal; Pekler, Gerald; Mushiyev, Savi; Pastori, Luciano J; Visco, Ferdinand; Aronow, Wilbert S

2015-01-01

Effectiveness of new oral anticoagulants (NOAC) in patients with cancer is not clearly defined. There remain concerns of doubtful benefit and chances of potential harm with newer agents. In this meta-analysis, we evaluated the efficacy and safety of NOAC in patients with cancer. PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched from January 01, 2001 through February 28, 2013. Randomized controlled trials reporting efficacy and safety data of NOACs (rivaroxaban, dabigatran, and apixaban) with control (low-molecular-weight heparin/vitamin K antagonists/placebo) for patients with cancer were included. Primary efficacy outcome was venous thromboembolism (VTE) or VTE-related death, and primary safety outcome was clinically relevant bleeding. We used random-effects models. Six trials randomized 19,832 patients, and 1197 patients had cancer. Risk of VTE or VTE-related death was not significantly different with NOAC versus control [odds ratio (OR), 0.80; 95% confidence interval (CI), 0.39-1.65] in patients with cancer. Separate analysis for individual effects showed similar results for rivaroxaban (OR, 1.08; 95% CI, 0.60-1.94) and dabigatran (OR, 0.91; 95% CI, 0.21-3.91). Clinically relevant bleeding was not higher with NOAC compared with control (OR, 1.49; 95% CI, 0.82-2.71); individual effect of rivaroxaban showed similar results. No statistically significant difference of efficacy and safety with NOAC was found between patients with and without cancer. Rivaroxaban might be equally effective and safe as vitamin K antagonist in patients with cancer. Dabigatran is as effective as comparator; however, safety profile of dabigatran is unknown. Randomized trials of new anticoagulants specific to the cancer population are necessary, and NOAC also need to be evaluated against low-molecular-weight heparin.

Effects of an educational technology on self-efficacy for breastfeeding and practice of exclusive breastfeeding.

PubMed

Javorski, Marly; Rodrigues, Andreyna Javorski; Dodt, Regina Cláudia Melo; Almeida, Paulo César de; Leal, Luciana Pedrosa; Ximenes, Lorena Barbosa

2018-06-11

To evaluate the effects of using a flipchart (serial album) on maternal self-efficacy in breastfeeding and its effects on exclusive breastfeeding (EBF) in children's first two months of life. Clinical trial in Recife, Northeastern Brazil, with 112 women in the third trimester of gestation, randomly distributed in intervention group (IG) and control group (CG). The intervention was the use of the flipchart in IG. Data collection was performed through interviews in the prenatal period, and telephone contact at second, fourth and eighth weeks postpartum. The Breastfeeding Self-Efficacy Scale-Short-Form (BSES-SF) was used to measure self-efficacy scores. In the analysis, was used descriptive, bivariate statistics through tests of comparisons of proportions and means, and relative risk assessment. There was a statistically significant difference in mean values of self-efficacy scores between women in the IG and CG (p<0.001) and in EBF rates (p<0.001). The probability of exclusively breastfeeding in IG was twice as high than in CG (RR 2.2, CI 1.51-3.21). The use of a flipchart as an educational tool had positive effects on self-efficacy scores for breastfeeding and in maintenance of EBF in the IG. Brazilian Registry of Clinical Trials: RBR-5N7K99.

Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines.

PubMed

Fowkes, Freya J I; Simpson, Julie A; Beeson, James G

2013-10-30

Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. The Malaria Vaccine Technology Roadmap's goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%'. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine.

Comparative Evaluation of the Efficacy of Probiotic, Herbal and Chlorhexidine Mouthwash on Gingival Health: A Randomized Clinical Trial

PubMed Central

Dodamani, Arun Suresh; Karibasappa, Gundabaktha; Khairnar, Mahesh Ravindra; Naik, Rahul Gaybarao; Jadhav, Harish Chaitram

2017-01-01

Introduction Due to inherent limitations of Chlorhexidine (CHX), search for an effective and potentially safe anti-plaque agent has led to emergence of alternative products. Aim The present study evaluated the comparative efficacy of probiotic, herbal and CHX mouthwashes on gingival health of healthy individuals. Materials and Methods The present study was randomized parallel group controlled trial. A group of 45 healthy subjects in the age group of 18-21 years received complete supragingival scaling at baseline and study variables viz., Oral Hygiene Index – Simplified (OHI-S), Plaque Index (PI) and Gingival Index (GI) were recorded. Subjects were then randomly divided into three groups (15 in each group) and were randomly intervened with three different mouthwashes i.e., HiOra mouthwash, CHX mouthwash and Probiotic mouthwash. Variables were again recorded on the seventh and 14th day after use of mouthwashes and data obtained was subjected to statistical analysis. Results There was no significant difference in the efficacy of CHX, HiOra regular and probiotic mouthwashes on plaque accumulation, gingival health and oral hygiene status. Conclusion Herbal and probiotic mouthwashes can prove to be effective alternatives to CHX with minimal side effects. PMID:28511500

Self-controlled clinical trial to evaluate the efficacy of Mukhakantivardhaka Lepa and Patoladi Ghanavati in Twakvaivarnya (hypermelanosis).

PubMed

Panigrahi, Madhumita; Vyas, Mahesh; Mohanty, Kabi Prasad

2017-01-01

Beauty is not only a source of joy but also gives confidence to some extent. Ayurvedic cosmetology starts from mother's womb and continues with Dinacharya (daily routines), Ratricharya (diet and regimen for night), Ritucharya (seasonal diet and regimen), etc. The symbiosis between cosmetology and Ayurveda is the most ancient one. With this research interest, the present study has been undertaken to assess the efficacy of Mukhakantivardhaka Lepa and Patoladi Ghanavati in Tvakvaivarnya (hypermelanosis). To evaluate the efficacy of Mukhakantivardhaka Lepa and Patoladi Ghanavati in Tvakvaivarnya (hypermelanosis). This study was a double-armed clinical trial in which 62 patients having signs and symptoms of Tvakvaivarnya were selected belonging to the age group of 16-40 years and received Mukhakantivardhaka Lepa and Patoladi Ghanavati for 60 days with follow-up after every week. For the purpose of perfect diagnosis and assessment of all aspects of the disease, a special research proforma was prepared. Both the groups showed 100% improvment in associated symptoms. Regarding the overall effect of therapy in both the groups, moderate improvement was high following marked improvement. No adverse reactions were documented. Mukhakantivardhaka Lepa and Patoladi Ghanavati work excellently on Tvakvaivarnya (hypermelanosis) and improve skin complexion.

The ongoing evolution of antibody-based treatments for Ebola virus infection.

PubMed

Mendoza, Emelissa J; Racine, Trina; Kobinger, Gary P

2017-03-01

The 2014-2016 Ebola virus outbreak in West Africa was the deadliest in history, prompting the evaluation of various drug candidates, including antibody-based therapeutics for the treatment of Ebola hemorrhagic fever (EHF). Prior to 2014, only convalescent blood products from EHF survivors had been administered to newly infected individuals as a form of treatment. However, during the recent outbreak, monoclonal antibody cocktails such as ZMapp, ZMAb and MB-003 were either tested in a human clinical safety and efficacy trial or provided to some based on compassionate grounds. This review aims to discuss the evolution of antibody-based treatments for EHF, their clinical trial efficacy and the development of new antibody-based therapies currently advancing in preclinical testing.

Cumulative proportion of responders analysis (CPRA) as a tool to assess treatment outcome in alcohol clinical trials.

PubMed

Falk, Daniel E; Litten, Raye Z; Anton, Raymond F; Kranzler, Henry R; Johnson, Bankole A

2014-03-01

Several definitions of treatment response have been proposed for alcohol clinical trials (e.g., abstinence and no heavy drinking). However, each of these outcomes allows only one definition of successful response. In contrast, the cumulative proportion of responders analysis (CPRA) includes all of the possible drinking response cutoff points, providing a more complete picture of the therapeutic effects of a treatment. CPRA has been used to examine the efficacy of analgesics but not alcohol pharmacotherapy. To demonstrate its potential utility, we conducted CPRA in two large alcohol treatment trials: the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) trial (naltrexone) and a multisite topiramate trial. CPRA was used to demonstrate the efficacy of naltrexone and topiramate on continuous measures of in-treatment drinking-heavy drinking days and drinks per day-and their reductions from pretreatment. All possible cutoff points were portrayed for each measure. We provide graphs to illustrate the effects of the active medications compared with placebo and examined them statistically over a number of salient drinking outcomes to evaluate their efficacy. Treatment group responder curves were not parallel across the entire range of cutoff points; rather, they separated only at lower levels of drinking. In general, effect sizes increased by 0.10-0.15 when going from the lowest drinking level cutoff (i.e., abstinence and no heavy drinking) to the cutoff associated with the maximal treatment effect. CPRA may be useful in designing subsequent trials and helping to illustrate for treatment providers the likelihood of treatment success given various definitions of a positive response.

Unexpected individual clinical site variation in eradication rates of group a streptococci by penicillin in multisite clinical trials.

PubMed

Kaplan, Edward L; Oakes, J Michael; Johnson, Dwight R

2007-12-01

Previously, we reported an unexpectedly large percentage of failures by penicillin to eradicate group A streptococci (GAS) from the upper respiratory tract. Because penicillin has been the recommended therapy for the treatment of GAS pharyngitis, our report prompted controversy. Data from clinical trials in which our laboratory has participated demonstrated marked variation in GAS eradication rates among clinical sites. The reasons for such variation have never been adequately examined. We performed statistical analyses of site variation in eradication rates to assess the potential effect on reported reduced penicillin efficacy. Penicillin GAS eradication rates were compared using data from 4 large multisite pharyngitis treatment trials (75 clinical sites; 1158 subjects). Variation in eradication rates among clinical sites was statistically evaluated [chi(2) tests and generalized estimating equation (GEE) regression models]. There was significant site-to-site variation in GAS eradication rates in each of the trials (range, 17-100%; P < 0.005) as well as between separate trials (mean range, 58-69%; P < 0.033). GEE modeling indicated that GAS eradication rates were significantly higher for clinical sites participating in more than one clinical trial. The statistically significant site-to-site variation in penicillin eradication rates was related to factors (dependencies) at individual sites. Such factors may affect assessment of therapeutic efficacy and indicate a necessity for considering clinical site variation before reporting pooled efficacy data from multiple sites; combined data may result in misleading clinical implications. This is the first report documenting significant variation resulting from individual clinical site-related factors and offers a possible explanation for reduced penicillin eradication.

Open trial of cimetidine in the prevention of upper gastro-intestinal haemorrhage in patients with severe intracranial injury.

PubMed

Mouawad, E; Deloof, T; Genette, F; Vandesteene, A

1983-01-01

The present study evaluates the efficacy of Cimetidine in the prevention of clinically important gastro-intestinal haemorrhage in patients suffering from severe head injury. Fifty patients (39 males and 11 females) were included in the study. We excluded from the trial patients on anticoagulant therapy or concomitant non-steroid anti-inflammatory agents, pregnant and lactating women, and patients with previous histories of peptic ulcer disease.

Efficacy and safety of available treatments for visceral leishmaniasis in Brazil: A multicenter, randomized, open label trial

PubMed Central

Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery; de Almeida, Roque Pacheco; de Melo, Enaldo Viera; de Carvalho, Sílvio Fernando Guimarães; Rabello, Ana; de Carvalho, Andréa Lucchesi; Sousa, Anastácio de Queiroz; Leite, Robério Dias; Lima, Simone Soares; Amaral, Thais Alves; Alves, Fabiana Piovesan; Rode, Joelle

2017-01-01

Background There is insufficient evidence to support visceral leishmaniasis (VL) treatment recommendations in Brazil and an urgent need to improve current treatments. Drug combinations may be an option. Methods A multicenter, randomized, open label, controlled trial was conducted in five sites in Brazil to evaluate efficacy and safety of (i) amphotericin B deoxycholate (AmphoB) (1 mg/kg/day for 14 days), (ii) liposomal amphotericin B (LAMB) (3 mg/kg/day for 7 days) and (iii) a combination of LAMB (10 mg/kg single dose) plus meglumine antimoniate (MA) (20 mg Sb+5/kg/day for 10 days), compared to (iv) standard treatment with MA (20 mg Sb+5/kg/day for 20 days). Patients, aged 6 months to 50 years, with confirmed VL and without HIV infection were enrolled in the study. Primary efficacy endpoint was clinical cure at 6 months. A planned efficacy and safety interim analysis led to trial interruption. Results 378 patients were randomized to the four treatment arms: MA (n = 112), AmphoB (n = 45), LAMB (n = 109), or LAMB plus MA (n = 112). A high toxicity of AmphoB prompted an unplanned interim safety analysis and this treatment arm was dropped. Per intention-to-treat protocol final analyses of the remaining 332 patients show cure rates at 6 months of 77.5% for MA, 87.2% for LAMB, and 83.9% for LAMB plus MA, without statistically significant differences between the experimental arms and comparator (LAMB: 9.7%; CI95% -0.28 to 19.68, p = 0.06; LAMB plus MA: 6.4%; CI95% -3.93 to 16.73; p = 0.222). LAMB monotherapy was safer than MA regarding frequency of treatment-related adverse events (AE) (p = 0.045), proportion of patients presenting at least one severe AE (p = 0.029), and the proportion of AEs resulting in definitive treatment discontinuation (p = 0.003). Conclusions Due to lower toxicity and acceptable efficacy, LAMB would be a more suitable first line treatment for VL than standard treatment. ClinicalTrials.gov identification number: NCT01310738. Trial registration ClinicalTrials.gov NCT01310738 PMID:28662034

The efficacy of a behavioral activation intervention among depressed US Latinos with limited English language proficiency: study protocol for a randomized controlled trial.

PubMed

Collado, Anahi; Long, Katherine E; MacPherson, Laura; Lejuez, Carl W

2014-06-18

Major depressive disorder is highly prevalent among Latinos with limited English language proficiency in the United States. Although major depressive disorder is highly treatable, barriers to depression treatment have historically prevented Latinos with limited English language proficiency from accessing effective interventions. The project seeks to evaluate the efficacy of behavioral activation treatment for depression, an empirically supported treatment for depression, as an intervention that may address some of the disparities surrounding the receipt of efficacious mental health care for this population. Following a pilot study of behavioral activation treatment for depression with 10 participants which yielded very promising results, the current study is a randomized control trial testing behavioral activation treatment for depression versus a supportive counseling treatment for depression. We are in the process of recruiting 60 Latinos with limited English language proficiency meeting criteria for major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th and 5th Edition for participation in a single-center efficacy trial. Participants are randomized to receive 10 sessions of behavioral activation treatment for depression (n = 30) or 10 sessions of supportive counseling (n = 30). Assessments occur prior to each session and at 1 month after completing treatment. Intervention targets include depressive symptomatology and the proposed mechanisms of behavioral activation treatment for depression: activity level and environmental reward. We will also examine other factors related to treatment outcome such as treatment adherence, treatment satisfaction, and therapeutic alliance. This randomized controlled trial will allow us to determine the efficacy of behavioral activation treatment for depression in a fast-growing, yet highly underserved population in US mental health services. The study is also among the first to examine the effect of the proposed mechanisms of change of behavioral activation treatment for depression (that is, activity level and environmental reward) on depression over time. To our knowledge, this is the first randomized controlled trial to compare an empirical-supported treatment to a control supportive counseling condition in a sample of depressed, Spanish-speaking Latinos in the United States. Clinical Trials Register: NCT01958840; registered 8 October 2013.

A multicentre phase III randomised controlled single-masked clinical trial evaluating the clinical efficacy and safety of light-masks at preventing dark-adaptation in the treatment of early diabetic macular oedema (CLEOPATRA): study protocol for a randomised controlled trial.

PubMed

Sivaprasad, Sobha; Arden, Geoffrey; Prevost, A Toby; Crosby-Nwaobi, Roxanne; Holmes, Helen; Kelly, Joanna; Murphy, Caroline; Rubin, Gary; Vasconcelos, Joanna; Hykin, Philip

2014-11-22

This study will evaluate hypoxia, as a novel concept in the pathogenesis of diabetic macular oedema (DMO). As the oxygen demand of the eye is maximum during dark-adaptation, we hypothesize that wearing light-masks during sleep will cause regression and prevent the development and progression of DMO. The study protocol comprises both an efficacy and mechanistic evaluation to test this hypothesis. This is a phase III randomised controlled single-masked multicentre clinical trial to test the clinical efficacy of light-masks at preventing dark-adaptation in the treatment of non-central DMO. Three hundred patients with non-centre-involving DMO in at least one eye will be randomised 1:1 to light-masks and control masks (with no light) to be used during sleep at night for a period of 24 months. The primary outcome is regression of non-central oedema by assessing change in the zone of maximal retinal thickness at baseline on optical coherence tomography (SD-OCT). Secondary outcomes will evaluate the prevention of development and progression of DMO by assessing changes in retinal thickness in different regions of the macula, macular volume, refracted visual acuity and level of retinopathy. Safety parameters will include sleep disturbance. Adverse events and measures of compliance will be assessed over 24 months. Participants recruited to the mechanistic sub-study will have additional retinal oximetry, multifocal electroretinography (ERG) and microperimetry to evaluate the role of hypoxia by assessing and comparing changes induced by supplemental oxygen and the light-masks at 12 months. The outcomes of this study will provide insight into the pathogenesis of DMO and provide evidence on whether a simple, non-invasive device in the form of a light-mask can help prevent the progression to centre-involving DMO and visual impairment in people with diabetes.

Efficacy and safety of Lian-Ju-Gan-Mao capsules for treating the common cold with wind-heat syndrome: study protocol for a randomized controlled trial.

PubMed

Wang, Shengjun; Jiang, Hongli; Yu, Qin; She, Bin; Mao, Bing

2017-01-05

The common cold is a common and frequent respiratory disease mainly caused by viral infection of the upper respiratory tract. Chinese herbal medicine has been increasingly prescribed to treat the common cold; however, there is a lack of evidence to support the wide utility of this regimen. This protocol describes an ongoing phase II randomized controlled clinical trial, based on the theory of traditional Chinese medicine (TCM), with the objective of evaluating the efficacy and safety of Lian-Ju-Gan-Mao capsules (LJGMC), a Chinese patent medicine, compared with placebo in patients suffering from the common cold with wind-heat syndrome (CCWHS). This is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial. A total of 240 patients will be recruited and randomly assigned to a high-dose group, medium-dose group, low-dose group, and placebo-matched group in a 1:1:1:1 ratio. The treatment course is 3 consecutive days, with a 5-day follow-up. The primary outcome is time to all symptoms' clearance. Secondary outcomes include time to the disappearance of primary symptoms and each secondary symptom, time to fever relief, time to fever clearance, and change in TCM symptom and sign scores. This trial is a well-designed study according to principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide high-quality evidence on the efficacy and safety of LJGMC in treating CCWHS and help to optimize the dose for the next phase III clinical trial. Moreover, the protocol presents a detailed and practical methodology for future clinical trials of drugs developed based on TCM. Chinese Clinical Trial Registry, ChiCTR-IPR-15006504 . Registered on 4 June 2015.

Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer's disease.

PubMed

Satlin, Andrew; Wang, Jinping; Logovinsky, Veronika; Berry, Scott; Swanson, Chad; Dhadda, Shobha; Berry, Donald A

2016-01-01

Recent failures in phase 3 clinical trials in Alzheimer's disease (AD) suggest that novel approaches to drug development are urgently needed. Phase 3 risk can be mitigated by ensuring that clinical efficacy is established before initiating confirmatory trials, but traditional phase 2 trials in AD can be lengthy and costly. We designed a Bayesian adaptive phase 2, proof-of-concept trial with a clinical endpoint to evaluate BAN2401, a monoclonal antibody targeting amyloid protofibrils. The study design used dose response and longitudinal modeling. Simulations were used to refine study design features to achieve optimal operating characteristics. The study design includes five active treatment arms plus placebo, a clinical outcome, 12-month primary endpoint, and a maximum sample size of 800. The average overall probability of success is ≥80% when at least one dose shows a treatment effect that would be considered clinically meaningful. Using frequent interim analyses, the randomization ratios are adapted based on the clinical endpoint, and the trial can be stopped for success or futility before full enrollment. Bayesian statistics can enhance the efficiency of analyzing the study data. The adaptive randomization generates more data on doses that appear to be more efficacious, which can improve dose selection for phase 3. The interim analyses permit stopping as soon as a predefined signal is detected, which can accelerate decision making. Both features can reduce the size and duration of the trial. This study design can mitigate some of the risks associated with advancing to phase 3 in the absence of data demonstrating clinical efficacy. Limitations to the approach are discussed.

The Impact of the Project K Youth Development Program on Self-Efficacy: A Randomized Controlled Trial.

PubMed

Deane, Kelsey L; Harré, Niki; Moore, Julie; Courtney, Matthew G R

2017-03-01

A key issue for youth development programs is whether the learning they provide is transferred to participants' daily lives. It is also important that they are effective for the diverse range of participants they attract. This study used a randomized controlled trial design to measure the impact of Project K, a New Zealand-based youth development program, on academic and social self-efficacy. Project K combines a 3-week wilderness adventure, a 10 day community service component, and 1 year of mentoring to promote positive growth in 14-15 year olds with low self-efficacy. At baseline, the evaluation included 600 Project K (46 % female) and 577 Control participants (48 % female) and revealed that Project K was effective in improving both social and academic self-efficacy from pre- to post-program with effects being sustained 1 year later. Parents' perceptions of changes in the participants' interpersonal skills supported these findings. Differential program effects were found across participant subgroups, particularly 1 year after program completion. The implications of these differences are discussed.

Preventing anxiety problems in children with Cool Little Kids Online: study protocol for a randomised controlled trial.

PubMed

Morgan, Amy J; Rapee, Ronald M; Tamir, Elli; Goharpey, Nahal; Salim, Agus; McLellan, Lauren F; Bayer, Jordana K

2015-11-05

Anxiety disorders are the most common type of mental health problem and begin early in life. Early intervention to prevent anxiety problems in young children who are at risk has the potential for long-term impact. The 'Cool Little Kids' parenting group program was previously established to prevent anxiety disorders in young children at risk because of inhibited temperament. This group program was efficacious in two randomised controlled trials and has recently been adapted into an online format. 'Cool Little Kids Online' was developed to widen and facilitate access to the group program's preventive content. A pilot evaluation of the online program demonstrated its perceived utility and acceptability among parents. This study aims to evaluate the efficacy of Cool Little Kids Online in a large randomised controlled trial. Parents of young children who are 3-6 years old and who have an inhibited temperament will be recruited (n = 385) and randomly assigned to either immediate access to Cool Little Kids Online or delayed access after a waiting period of 24 weeks. The online program contains eight modules that help parents address key issues in the development of anxiety problems in inhibited children, including children's avoidant coping styles, overprotective parenting behaviours, and parents' own fears and worries. Intervention participants will be offered clinician support when requested. The primary outcome will be change in parent-reported child anxiety symptoms. Secondary outcomes will be child internalising symptoms, child and family life interference due to anxiety, over-involved/protective parenting, plus child anxiety diagnoses assessed by using a new online diagnostic tool. Assessments will take place at baseline and 12 and 24 weeks after baseline. This trial expands upon previous research on the Cool Little Kids parenting group program and will evaluate the efficacy of online delivery. Online delivery of the program could result in an easily accessible evidence-based resource to help families with young children at temperamental risk for anxiety disorders. Australian New Zealand Clinical Trials Registry 12615000217505 (registered 5 March 2015).

Efficacy and safety of down-titration versus continuation strategies of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis with low disease activity or in remission: a systematic review and meta-analysis.

PubMed

Jiang, Mei; Ren, Feifeng; Zheng, Yaning; Yan, Ruyu; Huang, Wenhan; Xia, Ning; Luo, Lei; Zhou, Jun; Tang, Lin

2017-01-01

To evaluate the efficacy and safety of down-titration (dose reduction/tapering) strategies compared with continuation of biological disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who achieved and maintained low disease activity or remission. We searched the following electronic database up to March 2016: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and conference proceedings of the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR). Our meta-analysis included randomized controlled trials (RCTs) of RA patients with low disease activity or in remission that compared down-titration treatment with continuation treatment. Data on flare, defined as a 28-joint Disease Activity Score of ≥3.2, had to have been reported. Outcomes on efficacy or safety were collected. Of 1136 references identified, five RCTs (total, 771 participants) were included. The incidence of disease relapse in the down-titration and continuation groups was similar (risk ratio (RR)=1.14, 95% CI=0.88-1.49). There was no statistical difference in the number of serious adverse events (RR=1.15, 95% CI=0.53-2.49). Withdrawals due to inefficacy or toxicity were similar between groups and no clinically meaningful difference in efficacy outcomes was observed by continuation treatment. Our findings indicated that continuing a standard dose of biological DMARDs in patients with low disease activity conveyed no significant benefit as compared with down-titration therapy, suggesting that a down-titration strategy is as effective as a continuation strategy. Since the number of trials meeting the criteria for this meta-analysis was relatively low, future analyses with additional prospective RCTs are required to compare other biological agents and evaluate the long-term efficacy of these two strategies.

Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial.

PubMed

Willmott, C; Ponsford, J

2009-05-01

Most previous studies evaluating the use of methylphenidate following traumatic brain injury (TBI) have been conducted many years post-injury. This study evaluated the efficacy of methylphenidate in facilitating cognitive function in the inpatient rehabilitation phase. 40 participants with moderate-severe TBI (mean 68 days post-injury) were recruited into a randomised, crossover, double blind, placebo controlled trial. Methylphenidate was administered at a dose of 0.3 mg/kg twice daily and lactose in identical capsules served as placebo. Methylphenidate and placebo administration was randomised in a crossover design across six sessions over a 2 week period. Primary efficacy outcomes were neuropsychological tests of attention. No participants were withdrawn because of side effects or adverse events. Methylphenidate significantly increased speed of information processing on the Symbol Digit Modalities Test (95% CI 0.30 to 2.95, Cohen's d = 0.39, p = 0.02), Ruff 2 and 7 Test-Automatic Condition (95% CI 1.38 to 6.12, Cohen's d = 0.51, p = 0.003), Simple Selective Attention Task (95% CI -58.35 to -17.43, Cohen's d = 0.59, p = 0.001) and Dissimilar Compatible (95% CI -70.13 to -15.38, Cohen's d = 0.51, p = 0.003) and Similar Compatible (95% CI -74.82 to -19.06, Cohen's d = 0.55, p = 0.002) conditions of the Four Choice Reaction Time Task. Those with more severe injuries and slower baseline information processing speed demonstrated a greater drug response. Methylphenidate enhances information processing speed in the inpatient rehabilitation phase following TBI. This trial is registered with the Australian New Zealand Clinical Trials Registry (12607000503426).

Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development.

PubMed

Pinto, Ligia A; Dillner, Joakim; Beddows, Simon; Unger, Elizabeth R

2018-01-17

When administered as standard three-dose schedules, the licensed HPV prophylactic vaccines have demonstrated extraordinary immunogenicity and efficacy. We summarize the immunogenicity of these licensed vaccines and the most commonly used serology assays, with a focus on key considerations for one-dose vaccine schedules. Although immune correlates of protection against infection are not entirely clear, both preclinical and clinical evidence point to neutralizing antibodies as the principal mechanism of protection. Thus, immunogenicity assessments in vaccine trials have focused on measurements of antibody responses to the vaccine. Non-inferiority of antibody responses after two doses of HPV vaccines separated by 6 months has been demonstrated and this evidence supported the recent WHO recommendations for two-dose vaccination schedules in both boys and girls 9-14 years of age. There is also some evidence suggesting that one dose of HPV vaccines may provide protection similar to the currently recommended two-dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine schedules are lacking. In addition, immunogenicity has been assessed and reported using different methods, precluding direct comparison of results between different studies and vaccines. New head-to-head vaccine trials evaluating one-dose immunogenicity and efficacy have been initiated and an increase in the number of trials relying on immunobridging is anticipated. Therefore, standardized measurement and reporting of immunogenicity for the up to nine HPV types targeted by the current vaccines is now critical. Building on previous HPV serology assay standardization and harmonization efforts initiated by the WHO HPV LabNet in 2006, new secondary standards, critical reference reagents and testing guidelines will be generated as part of a new partnership to facilitate harmonization of the immunogenicity testing in new HPV vaccine trials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Feasibility and Efficacy of an mHealth Game for Managing Anxiety: "Flowy" Randomized Controlled Pilot Trial and Design Evaluation.

PubMed

Pham, Quynh; Khatib, Yasmin; Stansfeld, Stephen; Fox, Simon; Green, Tobias

2016-02-01

Meeting the complex needs of patients with chronic common mental health disorders (CMHDs) may be the greatest challenge facing organized medical practice. On the basis of a well-established and proven theoretical foundation for controlled respiration as a behavioral intervention for CMHDs, as well as preliminary evidence that gamification can improve health outcomes through increasing patient engagement, this randomized controlled pilot study evaluated the feasibility and clinical efficacy of a mobile health game called "Flowy" ( www.flowygame.com ) that digitally delivered breathing retraining exercises for anxiety, panic, and hyperventilation symptom management. We designed an unblinded, Web-based, parallel-group randomized controlled trial focusing on feasibility, clinical efficacy, and design proof of concept. In the intervention condition (n = 31), participants received free access to "Flowy" for 4 weeks. In the control condition (n = 32), participants were placed on a waitlist for 4 weeks before being offered free access to "Flowy." Online measurements using psychological self-report questionnaires were made at 2 and 4 weeks post-baseline. At trial conclusion, participants found "Flowy" acceptable as an anxiety management intervention. "Flowy" engaged participants sufficiently to endorse proactive gameplay. Intent-to-treat analysis revealed a reduction in anxiety, panic, and self-report hyperventilation scores in both trial arms, with the intervention arm experiencing greater quality of life. Participants perceived "Flowy" as a fun and useful intervention, proactively used "Flowy" as part of their care, and would recommend "Flowy" to family and friends. Our results suggest that a digital delivery of breathing retraining exercises through a mobile health game can manage anxiety, panic, and hyperventilation symptoms associated with CMHDs.

Planned development and evaluation protocol of two versions of a web-based computer-tailored nutrition education intervention aimed at adults, including cognitive and environmental feedback

PubMed Central

2014-01-01

Background Despite decades of nutrition education, the prevalence of unhealthy dietary patterns is still high and inequalities in intake between high and low socioeconomic groups still exist. Therefore, it is important to innovate and improve existing nutrition education interventions. This paper describes the development, design and evaluation protocol of a web-based computer-tailored nutrition education intervention for adults targeting fruit, vegetable, high-energy snack and fat intake. This intervention innovates existing computer-tailored interventions by not only targeting motivational factors, but also volitional and self-regulation processes and environmental-level factors. Methods/design The intervention development was guided by the Intervention Mapping protocol, ensuring a theory-informed and evidence-based intervention. Two versions of the intervention were developed: a basic version targeting knowledge, awareness, attitude, self-efficacy and volitional and self-regulation processes, and a plus version additionally addressing the home environment arrangement and the availability and price of healthy food products in supermarkets. Both versions consist of four modules: one for each dietary behavior, i.e. fruit, vegetables, high-energy snacks and fat. Based on the self-regulation phases, each module is divided into three sessions. In the first session, feedback on dietary behavior is provided to increase awareness, feedback on attitude and self-efficacy is provided and goals and action plans are stated. In the second session goal achievement is evaluated, reasons for failure are explored, coping plans are stated and goals can be adapted. In the third session, participants can again evaluate their behavioral change and tips for maintenance are provided. Both versions will be evaluated in a three-group randomized controlled trial with measurements at baseline, 1-month, 4-months and 9-months post-intervention, using online questionnaires. Both versions will be compared with a generic nutrition information control condition. The primary outcomes are fruit, vegetable, high-energy snack and fat intake. Discussion The evaluation study will provide insight into the short- and long-term efficacy of both intervention versions in adults. Additionally, differences in the efficacy among high- and low-educated people will be examined. If these interventions are effective, two well-developed interventions will become available for the implementation and promotion of healthy dietary patterns among both high- and low-educated adults in the Netherlands. Trial registration Dutch Trial Registry NTR3396. PMID:24438381

Smoking Cessation and Reduction in Schizophrenia (SCARIS) with e-cigarette: study protocol for a randomized control trial

PubMed Central

2014-01-01

Background It is well established in studies across several countries that tobacco smoking is more prevalent among schizophrenic patients than the general population. Electronic cigarettes are becoming increasingly popular with smokers worldwide. To date there are no large randomized trials of electronic cigarettes in schizophrenic smokers. A well-designed trial is needed to compare efficacy and safety of these products in this special population. Methods/Design Intervention: We have designed a randomized controlled trial investigating the efficacy and safety of electronic cigarette. The trial will take the form of a prospective 12-month randomized clinical study to evaluate smoking reduction, smoking abstinence and adverse events in schizophrenic smokers not intending to quit. We will also monitor quality of life, neurocognitive functioning and measure participants’ perception and satisfaction of the product. Outcome measures: A ≥50% reduction in the number of cigarettes/day from baseline, will be calculated at each study visit (“reducers”). Abstinence from smoking will be calculated at each study visit (“quitters”). Smokers who leave the study protocol before its completion and will carry out the Early Termination Visit or who will not satisfy the criteria of “reducers” and “quitters” will be defined “non responders”. Statistical analysis: The differences of continuous variables between the three groups will be evaluated with the Kruskal-Wallis Test, followed by the Dunn multiple comparison test. The differences between the three groups for normally distributed data will be evaluated with ANOVA test one way, followed by the Newman-Keuls multiple comparison test. The normality of the distribution will be evaluated with the Kolmogorov-Smirnov test. Any correlations between the variables under evaluation will be assessed by Spearman r correlation. To compare qualitative data will be used the Chi-square test. Discussion The main strengths of the SCARIS study are the following: it’s the first large RCT on schizophrenic patient, involving in and outpatient, evaluating the effect of a three-arm study design, and a long term of follow-up (52-weeks). The goal is to propose an effective intervention to reduce the risk of tobacco smoking, as a complementary tool to treat tobacco addiction in schizophrenia. Trial registration ClinicalTrials.gov, NCT01979796. PMID:24655473

Efficacy and safety of non-suture dural closure using a novel dural substitute consisting of polyglycolic acid felt and fibrin glue to prevent cerebrospinal fluid leakage-A non-controlled, open-label, multicenter clinical trial.

PubMed

Terasaka, Shunsuke; Taoka, Toshiaki; Kuroda, Satoshi; Mikuni, Nobutaka; Nishi, Toru; Nakase, Hiroyuki; Fujii, Yukihiko; Hayashi, Yasuhiko; Murata, Jun-Ichi; Kikuta, Ken-Ichiro; Kuroiwa, Toshihiko; Shimokawa, Sachie; Houkin, Kiyohiro

2017-05-01

The objective of this study is to evaluate the efficacy and safety of non-suture dural closure using a novel dural substitute (GM111) consisting of polyglycolic acid felt with a fibrin-glue-coated area commensurate in size with the dural defect. This was a non-controlled, open-label, multicenter clinical trial. The efficacy evaluation endpoints were (1) GM111's intra-operative capability to close dural defects and (2) prevention of cerebrospinal fluid (CSF) leakage and subcutaneous CSF retention throughout the postoperative period (evaluated by diagnostic imaging). Patients meeting the following three preoperative and two intra-operative selection criteria were enrolled: (1) between 12 and <75 years of age; (2) the dura is surmised to be defective and in need of reconstruction; (3) informed written consent was obtained from the patient; (4) the surgical wound is class 1; and (5) the size of duraplasty is ≥0.2 cm 2 to <100 cm 2 . Sixty patients were enrolled. The craniotomy site was supratentorial in 77.2%, infratentorial in 12.3% and sellar in 10.5%. The GM111 prosthesis size ranged from 0.24 to 42 cm 2 . To evaluate the efficacy, intra-operative closure was confirmed by Valsalva's maneuver, water infusion, etc., in all patients. CSF leakage and subcutaneous CSF retention throughout the postoperative period were found in four patients. Adverse events for which a causal relationship with GM111 could not be ruled out occurred in 8.8% of the patients. There were no instances of postoperative infection due to GM111. GM111 showed good closure capability and safety when used for non-suture dural closure.

Efficacy of Therapies for Postural Tachycardia Syndrome: A Systematic Review and Meta-analysis.

PubMed

Wells, Rachel; Elliott, Adrian D; Mahajan, Rajiv; Page, Amanda; Iodice, Valeria; Sanders, Prashanthan; Lau, Dennis H

2018-06-21

To identify the evidence base and evaluate the efficacy of each treatment for postural tachycardia syndrome (POTS) in light of a recent consensus statement highlighting the lack of treatment options with clear benefit to risk ratios for this debilitating condition. The CENTRAL (Cochrane Central Register of Controlled Trials), PubMed, and Embase databases from inception to May 2017 were searched using the terms postural AND tachycardia AND syndrome. A total of 135 full-text publications were screened after excluding duplicates (n=681), conference abstracts (n=467), and records that did not relate to POTS therapy (n=876). We included 28 studies with at least 4 patients with POTS in which symptomatic response was reported after more than 4 weeks of therapy. This review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Two investigators independently performed the data extraction and evaluated the quality of evidence. This study comprised 25 case series and 3 small randomized controlled trials that evaluated 755 and 103 patients with POTS, respectively. Interventions directed at increasing intravascular volume, increasing peripheral or splanchnic vascular tone, controlling heart rate, and increasing exercise tolerance demonstrate moderate efficacy (range, 51%-72%). Few data exist on their comparative effectiveness. Significant heterogeneities were seen in terms of patient age, symptom severity, and the measures used to evaluate treatment efficacy. The current evidence base to guide optimal management of patients with POTS is extremely limited. More high-quality collaborative research with standardized reporting of symptom response and treatment tolerability is urgently needed. Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Acupuncture as prophylaxis for menstrual-related migraine: study protocol for a multicenter randomized controlled trial

PubMed Central

2013-01-01

Background Menstrual-related migraine is a common form of migraine affecting >50% of female migraineurs. Acupuncture may be a choice for menstrual-related migraine, when pharmacological prophylaxis is not suitable. However, the efficacy of acupuncture has not been confirmed. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with naproxen in menstrual-related migraine patients. Methods/Design This is a multicenter, single blind, randomized controlled clinical trial. A total of 184 participants will be randomly assigned to two different groups. Participants will receive verum acupuncture and placebo medicine in the treatment group, while participants in the control group will be treated with sham acupuncture and medicine (Naproxen Sustained Release Tablets). All treatments will be given for 3 months (menstrual cycles). The primary outcome measures are the change of migraine days inside the menstrual cycle and the proportion of responders (defined as the proportion of patients with at least a 50% reduction in the number of menstrual migraine days). The secondary outcome measures are the change of migraine days outside the menstrual cycle, duration of migraine attack, the Visual Analogue Scale (VAS), and intake of acute medication. The assessment will be made at baseline (before treatment), 3 months (menstrual cycles), and 4 months (menstrual cycles) after the first acupuncture session. Discussion The results of this trial will be helpful to supply the efficacy of acupuncture for menstrual-related migraine prophylaxis. Trial registration ISRCTN: ISRCTN57133712 PMID:24195839

Effectiveness outcomes in attention-deficit/hyperactivity disorder.

PubMed

Weiss, Margaret D; Gadow, Kenneth; Wasdell, Michael B

2006-01-01

Attention-deficit/hyperactivity disorder (ADHD) is common, chronic, and associated with significant functional impairment. It is highly treatable. It is therefore not only a major public health problem but also one that provides a unique opportunity in medicine to make a significant difference. This article will discuss the methodology needed to demonstrate empirically the impact of treatment on actual burden of illness in practice. Where efficacy studies demonstrate whether a treatment can work, effectiveness studies tell us whether they actually do work. Clinical trials exclude incompetent, non-compliant, and seriously comorbid patients, so that the information obtained from these trials tells us the most about the patients we see the least. Small differences in effect size in pivotal trials of efficacy have become a key variable for rating treatments as first line or second line, without consideration of effectiveness variables such as comorbidity, difficulty with appetite or sleep, patient preference, capacity for compliance, timing of functional impairment, and substance use. These effectiveness variables are less well studied, but critical to clinical decision making. In reality, fewer than 10% of our patients comply with and persist with treatment. To learn more about why patients are discontinuing treatment, we need to explore measures of effectiveness empirically. Effectiveness studies are also important to provide regulatory bodies with the data they need to balance the risk of treatment with the risk of failing to treat. Practical clinical trials and naturalistic follow-up studies will allow us to evaluate the true clinical impact of short-term efficacy trials.

Interventions for preventing late postnatal mother-to-child transmission of HIV.

PubMed

Horvath, Tara; Madi, Banyana C; Iuppa, Irene M; Kennedy, Gail E; Rutherford, George; Read, Jennifer S

2009-01-21

Worldwide, mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV) represents the most common means by which children acquire HIV infection. Efficacious and effective interventions to prevent in utero and intrapartum transmission of HIV infection have been developed and implemented. However, a large proportion of MTCT of HIV occurs postnatally, through breast milk transmission. The objectives of this systematic review were to collate and assess the evidence regarding interventions to decrease late postnatal MTCT of HIV, and to determine the efficacy of such interventions in decreasing late postnatal MTCT of HIV, increasing overall survival, and increasing HIV-free survival. Electronic searches were undertaken using PubMed, EMBASE and other databases for 1980-2008. Hand searches of reference lists of pertinent reviews and studies, as well as abstracts from relevant conferences, were also conducted. Experts in the field were contacted to locate any other studies. The search strategy was iterative. Randomized clinical trials assessing the efficacy of interventions to prevent MTCT of HIV through breast milk were included in the analysis. Other trials and intervention cohort studies with relevant data also were included, but only when randomization was not feasible due to the nature of the intervention (i.e., infant feeding modality). Data regarding HIV infection status and vital status of infants born to HIV-infected women, according to intervention, were extracted from the reports of the studies. Six randomized clinical trials and one intervention cohort study were included in this review. Two trials addressed the issue of shortening the duration of (or eliminating) exposure to breast milk. In a trial of breastfeeding versus formula feeding, formula feeding was efficacious in preventing MTCT of HIV (the cumulative probability of HIV infection at 24 months was 36.7% in the breastfeeding arm and 20.5% in the formula arm [p = 0.001]), but the mortality and malnutrition rates during the first two years of life were similar in the two groups. In a trial of early cessation of breastfeeding, HIV-free survival was similar between those children who ceased breastfeeding around four months of age and those who continued breastfeeding. Another trial addressing vitamin supplementation found more cases of HIV infection among children of mothers in the vitamin A arm. Efficacy for other vitamin supplements was not shown. An intervention cohort study evaluated the risk of MTCT according to infant feeding modality, and found increased risks of MTCT among breastfed children who also received solids (hazard ratio = 10.87, p = 0.018) as well as higher 3-month mortality rates (hazard ratio = 2.06) among infants given non- breast milk feedings (instead of exclusive breastfeeding). Three trials evaluated antiretroviral prophylaxis to breastfeeding infants. One trial found that breastfeeding with zidovudine prophylaxis (transmission rate = 9.0%) was not as effective as formula feeding (transmission rate 5.6%) in preventing late postnatal HIV transmission (p = 0.04). Breastfeeding with zidovudine prophylaxis and formula feeding had comparable HIV-free survival rates at 18 months (p = 0.60). Two trials of extended nevirapine prophylaxis demonstrated efficacy. In the first (data combined from trials conducted in three different countries), a six-week course of nevirapine resulted in a lower risk of HIV transmission by six weeks of age (p=0.009), but not at six months of age (p = 0.016). In the second, nevirapine administration until 14 weeks of age (5.2%) or nevirapine with zidovudine until 14 weeks of age (6.4%) resulted in significantly lower risks of MTCT of HIV by 9 months of age than a control regimen of peripartum prophylaxis (10.6%) (p < 0.001). HIV-free survival was significantly better through the age of 9 months in both extended prophylaxis groups, and through the age of 15 months in the extended nevirapine group. Complete avoidance of breastfeeding is efficacious in preventing MTCT of HIV, but this intervention has significant associated morbidity (e.g., diarrheal morbidity if formula is prepared without clean water). If breastfeeding is initiated, two interventions 1). exclusive breastfeeding during the first few months of life; and 2) chronic antiretroviral prophylaxis to the infant (nevirapine alone, or nevirapine with zidovudine) are efficacious in preventing transmission.

Efficacy of a DVD-Based Smoking Cessation Intervention for African Americans

PubMed Central

Baker, Elizabeth A.; Robinson, Robert G.

2014-01-01

Introduction: Previous research suggests that African American smokers may have improved outcomes if interventions are culturally specific. However, few interventions sufficiently address the unique needs of this population in a format with large reach potential. The purpose of this study was to test the efficacy of a newly developed digital video disc (DVD)-based cessation intervention targeting African Americans. Methods: In a 2-arm randomized trial, smokers (N = 140) were randomly assigned to view either the new Pathways to Freedom (PTF) DVD or a standard control DVD. Participants were assessed at baseline, immediately postviewing the DVD, and at a 1-month follow-up. The primary outcomes were feasibility and process variables, including intervention evaluations, readiness to quit, and risk perceptions, and smoking-related behavior changes were examined as secondary outcomes. Results: Findings demonstrated the hypothesized positive effects of the PTF DVD compared with the control DVD on content evaluations, risk perceptions, and readiness to quit at follow-up. Conclusions: We found initial evidence for the efficacy of the PTF DVD as a stand-alone intervention. Future research will test the efficacy of the DVD for smoking cessation in a larger randomized trial. The ultimate goal of this research is to validate a new intervention for an underserved community of smokers that can be used in multiple settings, such as community health clinics, primary care, quitlines, cessation clinics, and seminars/workshops. PMID:24838844

The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics

PubMed Central

2013-01-01

Background The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. Methods This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Results Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. Conclusion This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. Trial Registration ClinicalTrials.gov: NCT00112398 PMID:24034628

Tumor shrinkage and objective response rates: gold standard for oncology efficacy screening trials, or an outdated end point?

PubMed

Bradbury, Penelope; Seymour, Lesley

2009-01-01

Phase II clinical trials have long been used to screen new cancer therapeutics for antitumor activity ("efficacy") worthy of further evaluation. Traditionally, the primary end point used in these screening trials has been objective response rate (RR), with the desired rate being arbitrarily set by the researchers before initiation of the trial. For cytotoxic agents, especially in common tumor types, response has been a reasonably robust and validated surrogate of benefit. Phase II trials with response as an end point have a modest sample size (15-40 patients) and are completed rapidly allowing early decisions regarding future development of a given agent. More recently, a number of new agents have proven successful in pivotal phase III studies, despite a low or very modest RR demonstrated in early clinical trials. Researchers have postulated that these novel agents, as a class, may not induce significant regression of tumors, and that the use of RR as an end point for phase II studies will result in false negative results, and point out that not all available data is used in making the decision. Others have pointed out that even novel agents have proven unsuccessful in pivotal trials if objective responses are not demonstrated in early clinical trials. We review here the historical and current information regarding objective tumor response.

Innovations in Clinical Trial Design in the Era of Molecular Profiling.

PubMed

Wulfkuhle, Julia D; Spira, Alexander; Edmiston, Kirsten H; Petricoin, Emanuel F

2017-01-01

Historically, cancer has been studied, and therapeutic agents have been evaluated based on organ site, clinical staging, and histology. The science of molecular profiling has expanded our knowledge of cancer at the cellular and molecular level such that numerous subtypes are being described based on biomarker expression and genetic mutations rather than traditional classifications of the disease. Drug development has experienced a concomitant revolution in response to this knowledge with many new targeted therapeutic agents becoming available, and this has necessitated an evolution in clinical trial design. The traditional, large phase II and phase III adjuvant trial models need to be replaced with smaller, shorter, and more focused trials. These trials need to be more efficient and adaptive in order to quickly assess the efficacy of new agents and develop new companion diagnostics. We are now seeing a substantial shift from the traditional multiphase trial model to an increase in phase II adjuvant and neoadjuvant trials in earlier-stage disease incorporating surrogate endpoints for long-term survival to assess efficacy of therapeutic agents in shorter time frames. New trial designs have emerged with capabilities to assess more efficiently multiple disease types, multiple molecular subtypes, and multiple agents simultaneously, and regulatory agencies have responded by outlining new pathways for accelerated drug approval that can help bring effective targeted therapeutic agents to the clinic more quickly for patients in need.

Effectiveness of Chinese massage therapy (Tui Na) for chronic low back pain: study protocol for a randomized controlled trial.

PubMed

Yang, Mingxiao; Feng, Yue; Pei, Hong; Deng, Shufang; Wang, Minyu; Xiao, Xianjun; Zheng, Hui; Lai, Zhenhong; Chen, Jiao; Li, Xiang; He, Xiaoguo; Liang, Fanrong

2014-10-29

Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP. The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire. The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy. This trial was registered with ClinicalTrials.gov of the National Institute of Health on 22 October 2013 (http://NCT01973010).

Effectiveness of Treatment Approaches for Children and Adolescents with Reading Disabilities: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Galuschka, Katharina; Ise, Elena; Krick, Kathrin; Schulte-Körne, Gerd

2014-01-01

Children and adolescents with reading disabilities experience a significant impairment in the acquisition of reading and spelling skills. Given the emotional and academic consequences for children with persistent reading disorders, evidence-based interventions are critically needed. The present meta-analysis extracts the results of all available randomized controlled trials. The aims were to determine the effectiveness of different treatment approaches and the impact of various factors on the efficacy of interventions. The literature search for published randomized-controlled trials comprised an electronic search in the databases ERIC, PsycINFO, PubMed, and Cochrane, and an examination of bibliographical references. To check for unpublished trials, we searched the websites clinicaltrials.com and ProQuest, and contacted experts in the field. Twenty-two randomized controlled trials with a total of 49 comparisons of experimental and control groups could be included. The comparisons evaluated five reading fluency trainings, three phonemic awareness instructions, three reading comprehension trainings, 29 phonics instructions, three auditory trainings, two medical treatments, and four interventions with coloured overlays or lenses. One trial evaluated the effectiveness of sunflower therapy and another investigated the effectiveness of motor exercises. The results revealed that phonics instruction is not only the most frequently investigated treatment approach, but also the only approach whose efficacy on reading and spelling performance in children and adolescents with reading disabilities is statistically confirmed. The mean effect sizes of the remaining treatment approaches did not reach statistical significance. The present meta-analysis demonstrates that severe reading and spelling difficulties can be ameliorated with appropriate treatment. In order to be better able to provide evidence-based interventions to children and adolescent with reading disabilities, research should intensify the application of blinded randomized controlled trials. PMID:24587110

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients

PubMed Central

Yang, Juan; Li, Lu-jin; Wang, Kun; He, Ying-chun; Sheng, Yu-cheng; Xu, Ling; Huang, Xiao-hui; Guo, Feng; Zheng, Qing-shan

2011-01-01

Aim: To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Methods: Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. Results: Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple Emax model with a fixed E0, which provided a common Emax and an approximate twofold difference in ED50 for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. Conclusion: The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries. PMID:21151159

Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients.

PubMed

Yang, Juan; Li, Lu-jin; Wang, Kun; He, Ying-chun; Sheng, Yu-cheng; Xu, Ling; Huang, Xiao-hui; Guo, Feng; Zheng, Qing-shan

2011-01-01

To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple E(max) model with a fixed E(0), which provided a common E(max) and an approximate twofold difference in ED(50) for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries.

Brivaracetam: An Adjunctive Treatment for Partial-Onset Seizures.

PubMed

Kappes, John A; Hayes, William J; Strain, Joe D; Farver, Debra K

2017-07-01

Brivaracetam is an analogue of levetiracetam that is Food and Drug Administration-approved for adjunctive treatment of partial-onset seizures in patients 16 years and older. In placebo-controlled trials adjunct brivaracetam demonstrated efficacy in reducing the frequency of seizures. The most commonly reported adverse effects are somnolence, dizziness, and fatigue. Clinical trials have evaluated brivaracetam for safety and efficacy in adjunctive treatment of partial-onset seizures in patients 16 years and older for up to 16 weeks. Brivaracetam's mechanism is similar to that of levetiracetam but with greater receptor binding affinity on synaptic vesicle protein 2A and inhibitory effects on sodium channels. Clinically significant differences between these agents are undetermined. Brivaracetam is available as oral tablets, oral solution, and intravenous solution. The Food and Drug Administration-approved dose is 50 mg twice daily, and titration is not required. Brivaracetam does not need dose adjustment for renal impairment and has minimal drug-drug interactions. Current limitations of brivaracetam include lack of head-to-head trials, limited long-term safety and efficacy data, and cost. Overall, brivaracetam is a viable adjunct therapeutic option for refractory partial-onset seizures in those who have failed conventional therapies. © 2017, The American College of Clinical Pharmacology.

Safety and Efficacy of Rivastigmine in Adolescents with Down Syndrome: Long-Term Follow-Up

PubMed Central

Spiridigliozzi, Gail A.; Crissman, Blythe G.; McKillop, Jane Anne; Yamamoto, Haru; Kishnani, Priya S.

2010-01-01

Abstract Following the completion of a 20-week, open-label study of the safety and efficacy of liquid rivastigmine for adolescents with Down syndrome, 5 of the 10 adolescents in the clinical trial continued long-term rivastigmine therapy and 5 did not. After an average period of 38 months, all 10 subjects returned for a follow-up assessment to determine the safety and efficacy of long-term rivastigmine use. Rivastigmine was well tolerated and overall health appeared to be unaffected by long-term rivastigmine use. Performance change on cognitive and language measures administered at the termination of the open-label clinical trial was compared between the two groups. No between-group difference in median performance change across the long-term period was found, suggesting that the long-term use of rivastigmine does not improve cognitive and language performance. However, two subjects demonstrated remarkable improvement in adaptive function over the long-term period. Both subjects had received long-term rivastigmine therapy. The discussion addresses the challenge of assessing cognitive change in clinical trials using adolescents with Down syndrome as subjects and the use of group versus individual data to evaluate the relevance of medication effects. PMID:21186971

A systematic review of microwave-based therapy for axillary hyperhidrosis.

PubMed

Hsu, Tzu-Herng; Chen, Yu-Tsung; Tu, Yu-Kang; Li, Chien-Nien

2017-10-01

To systematically analyse the literature on the use of the microwave-based device for subdermal thermolysis of the axilla and its efficacy for the treatment of axillary hyperhidrosis. A systematic review was conducted using PubMed, Embase, SCOPUS and Cochrane databases on 2 June 2016. The inclusion criteria including: (1) studies with human subjects, (2) full-text articles published in English, (3) a microwave-based device used to treat axillary hyperhidrosis and (4) trials that precisely evaluated axillary hyperhidrosis. Exclusion criteria were the following: (1) studies that did not fit the inclusion criteria mentioned above and (2) case reports and reviews. We reviewed five clinical trials and 189 patients, all of which were published between 2012 and 2016. There was one randomized controlled trial, one retrospective study and the remainder were prospective studies. Although all of the studies were conducted with a small sample size, the results indicated that microwave-based device treatment of axillary hyperhidrosis had long-term efficacy with mild adverse effects. In addition, most patients were satisfied with the outcomes in these studies. Microwave-based device treatment may be an effective alternative treatment for axillary hyperhidrosis. However, further investigation is necessary to determine its long-term efficacy and safety.

Feasibility trial of a Spanish-language multimedia educational intervention.

PubMed

Wells, Kristen J; McIntyre, Jessica; Gonzalez, Luis E; Lee, Ji-Hyun; Fisher, Kate J; Jacobsen, Paul B; Meade, Cathy; Muñoz-Antonia, Teresita; Quinn, Gwendolyn P

2013-10-01

Hispanic cancer patients are underrepresented in clinical trials; research suggests lack of knowledge and language barriers contribute to low accrual. Multimedia materials offer advantages to Hispanic populations because they have high acceptability, are easy to disseminate, and can be viewed with family. Hispanic cancer patients and caregivers participated in focus groups to aid in developing a Spanish-language multimedia intervention to educate Hispanic cancer patients about clinical trials. We explored the feasibility of delivering the intervention in medical oncology clinics. A total of 35 patients were randomized to either the multimedia intervention group (n = 18) or a control group (n = 17) who were asked to read the National Cancer Institute's Spanish-language clinical trials brochure. Self-reported data on knowledge about and attitudes toward clinical trials, self-efficacy for participating in a clinical trial, intention to participate in a clinical trial if asked, and receptivity to information about a clinical trial were collected at baseline and 10 days later. Delivery of the multimedia presentation in oncology clinics was feasible. The intervention group had more knowledge about clinical trials at follow-up than the control group; scores for intention to participate in a clinical trial by participants in the intervention group increased from 3.8 to 4.0 of a possible 5, but declined in the control group from 4.5 to 4.1. No statistically significant difference was detected between groups in scores for attitudes or self-efficacy for making a decision to participate in a clinical trial. Our sample size was inadequate to identify differences between the informational methods. Although all patients were asked about their willingness to participate in a clinical trial, this decision was hypothetical. In addition, the study was conducted with a sample of Spanish-speaking Hispanic cancer patients at a comprehensive cancer center in Florida. Thus, the results may not generalize to other Hispanic populations. In the pilot project, we demonstrated the feasibility of delivering multimedia information to patients in medical oncology clinics. Because delivery in a clinical setting was found to be feasible, a larger study should be conducted to evaluate the efficacy of the multimedia intervention with respect to promoting accrual of Hispanic patients to clinical trials.

The Efficacy of Psychological Therapies in Reducing Weight and Binge Eating in People with Bulimia Nervosa and Binge Eating Disorder Who Are Overweight or Obese—A Critical Synthesis and Meta-Analyses

PubMed Central

Palavras, Marly Amorim; Hay, Phillipa; dos Santos Filho, Celso Alves; Claudino, Angélica

2017-01-01

Recurrent binge eating episodes, the core feature of Bulimia Nervosa (BN) and Binge Eating Disorder (BED), are frequently comorbid with obesity. Psychological interventions, notably Cognitive Behavioural Therapy (CBT), are effective for binge eating reduction in BED or BN but less so for weight loss. Behavioural Weight Loss Therapy (BWLT) shows effectiveness for binge eating reduction and weight loss but the latter appears poorly sustained over time. Our aim was to review evidence for efficacy of psychological therapies for BN/BED associated with overweight or obesity in reducing binge frequency and weight. A systematic search for randomized controlled trials with adult samples who had BN or BED was conducted considering articles in English, French, Spanish and Portuguese with no restrictions for the timeline publication ending in March 2016. A quality appraisal of the trials and meta-analyses comparing BWLT to CBT were done. This review identified 2248 articles for screening and 19 published articles were selected. No trials of BN were identified. This review found CBT was favoured compared to BWLT with regard to short-term binge eating reduction. However, insufficient evidence was found for superiority for BWLT efficacy compared to CBT considering binge eating remission, reduction of binge eating frequency and weight loss. More research is needed to test the efficacy of psychological treatments for BED or BN with co-morbid overweight or obesity, including trials evaluating binge eating remission and weight loss in the long-term. PMID:28304341

The Efficacy of Psychological Therapies in Reducing Weight and Binge Eating in People with Bulimia Nervosa and Binge Eating Disorder Who Are Overweight or Obese-A Critical Synthesis and Meta-Analyses.

PubMed

Palavras, Marly Amorim; Hay, Phillipa; Filho, Celso Alves Dos Santos; Claudino, Angélica

2017-03-17

Recurrent binge eating episodes, the core feature of Bulimia Nervosa (BN) and Binge Eating Disorder (BED), are frequently comorbid with obesity. Psychological interventions, notably Cognitive Behavioural Therapy (CBT), are effective for binge eating reduction in BED or BN but less so for weight loss. Behavioural Weight Loss Therapy (BWLT) shows effectiveness for binge eating reduction and weight loss but the latter appears poorly sustained over time. Our aim was to review evidence for efficacy of psychological therapies for BN/BED associated with overweight or obesity in reducing binge frequency and weight. A systematic search for randomized controlled trials with adult samples who had BN or BED was conducted considering articles in English, French, Spanish and Portuguese with no restrictions for the timeline publication ending in March 2016. A quality appraisal of the trials and meta-analyses comparing BWLT to CBT were done. This review identified 2248 articles for screening and 19 published articles were selected. No trials of BN were identified. This review found CBT was favoured compared to BWLT with regard to short-term binge eating reduction. However, insufficient evidence was found for superiority for BWLT efficacy compared to CBT considering binge eating remission, reduction of binge eating frequency and weight loss. More research is needed to test the efficacy of psychological treatments for BED or BN with co-morbid overweight or obesity, including trials evaluating binge eating remission and weight loss in the long-term.

Efficacy and safety of laxatives for chronic constipation in long-term care settings: A systematic review.

PubMed

Alsalimy, N; Madi, L; Awaisu, A

2018-06-09

Constipation is a common disorder among long-term care (LTC) patients due to several factors. However, there are no systematic reviews investigating the use of laxatives for chronic constipation in LTC settings. This study aims to explore the safety and efficacy of laxatives in LTC patients. A systematic review of randomized controlled trials (RCTs) describing the efficacy and safety of laxatives for chronic constipation in LTC patients was conducted using the following databases and search engines: MEDLINE, Cochrane Database of Systematic Reviews, ScienceDirect, ProQuest and Google Scholar. Two of the investigators independently performed the searches, and the data were extracted using a standardized data abstraction tool. Seven RCTs involving 444 patients were included in the review. These studies included senna (with or without fibre, ie Plantago ovata), lactulose, sodium picosulphate, docusate sodium, docusate calcium, isotonic and hypotonic polyethylene glycol and Chinese herbal medicine. Senna and lactulose were the most studied laxatives in LTC patients, and senna was found to be superior to or as effective as other laxatives. Generally, the frequency and severity of adverse drug reactions (ADRs) were similar between the arms of the studies, and no serious ADRs were reported. Considering the short duration of the trials, the lack of trials including newer laxatives and the low quality of some of the included trials, the long-term efficacy and safety of these laxatives are not conclusive. There is a need to conduct more robust RCTs that include newer agents to evaluate long-term outcomes. © 2018 John Wiley & Sons Ltd.

Efficacy and safety of liraglutide, a once-daily human glucagon-like peptide-1 analogue, in Latino/Hispanic patients with type 2 diabetes: post hoc analysis of data from four phase III trials.

PubMed

Davidson, J A; Ørsted, D D; Campos, C

2016-07-01

The aim of the present analysis was to evaluate the efficacy of the glucagon-like peptide-1 receptor agonist liraglutide in Latino/Hispanic individuals with type 2 diabetes, in addition to comparing its treatment effects with those observed in non-Latino/Hispanic individuals. Analyses were performed on patient-level data from a subset of individuals self-defined as Latino/Hispanic from four phase III studies, the LEAD-3, LEAD-4, LEAD-6 and 1860-LIRA-DPP-4 trials. Endpoints included change in glycated haemoglobin (HbA1c) and body weight from baseline. In Latino/Hispanic patients (n = 505; 323 treated with liraglutide) after 26 weeks, mean HbA1c reductions were significantly greater with both liraglutide 1.2 and 1.8 mg versus comparator or placebo in the LEAD-3 and LEAD-4 studies, and with 1.8 mg liraglutide in the 1860-LIRA-DPP-4 trial. In LEAD-3 both doses led to significant differences in body weight change among Latino/Hispanic patients versus the comparator. With 1.8 mg liraglutide, difference in weight change was significant only in the 1860-LIRA-DPP-4 trial versus sitagliptin. For both endpoints Latino/Hispanic and non-Latino/Hispanic patients responded to liraglutide similarly. In summary, liraglutide is efficacious for treatment of type 2 diabetes in Latino/Hispanic patients, with a similar efficacy to that seen in non-Latino/Hispanic patients. © 2016 John Wiley & Sons Ltd.

Correlation between sex and efficacy of immune checkpoint inhibitors (PD-1 and CTLA-4 inhibitors).

PubMed

Wu, Yingcheng; Ju, Qianqian; Jia, Keren; Yu, Jingyan; Shi, Hui; Wu, Huiqun; Jiang, Maorong

2018-07-01

Immune checkpoint inhibitors (ICIs) exert the antitumor efficacy depending on immune response, which is affected by sex difference, where both biological and sociological factors are involved. The role of sex in ICI trials has been overlooked. How sex correlates with ICI efficacy is incompletely understood. Clinical trials evaluating ICI versus other therapies in male and female patients were included. The hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) were used. Six thousand and ninety-six patients from 11 trials were included. More improvement of OS was observed in males (HR, 0.62; 95% CI, 0.53-0.71; p < 0.001) treated with ICI versus controls than females (HR, 0.74; 95% CI, 0.65-0.84; p < 0.001). ICIs improved PFS more in males (HR, 0.57; 95% CI, 0.43-0.71; p < 0.001) than females (HR, 0.71; 95% CI, 0.52-0.91; p < 0.001). The sex difference had more effect on the overall survival in melanoma patients versus NSCLC patients. Overall survival of patients treated with CTLA-4 inhibitor was more influenced by sex variable compared with PD-1 inhibitors. A significant sex-related efficacy difference was observed between female and male melanoma patients. Although male patients had longer OS and PFS than females when treated with ICIs versus controls, the difference was not significant. Sex difference should be more considered in future clinical trials, guidelines and clinical practice. © 2018 UICC.

An Evaluation of the Effectiveness of Recruitment Methods: The Staying Well after Depression Randomized Controlled Trial

PubMed Central

Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J. Mark G.

2014-01-01

Background Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited and trials often fail to report sufficient details about the recruitment sources and resources utilised. Purpose We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. Methods We describe eight recruitment methods utilised and two further sources not initiated by the research team and examine their efficacy in terms of (i) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial, (ii) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants, and (iii) comparison of sociodemographic characteristics of individuals recruited from different sources. Results Poster advertising, web-based advertising and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. Limitations It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in other geographical locations. Recruitment source was unavailable for participants who could not be reached after the initial contact. Thus, it is possible that the efficiency of certain methods of recruitment was poorer than estimated. Efficacy and costs of other recruitment initiatives, such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to candidates who contacted the recruitment team but could not be screened promptly, were not analysed. Conclusions Website advertising resulted in the highest number of randomized participants and was the second cheapest method of recruiting. Future research should evaluate the effectiveness of recruitment strategies for other samples to contribute to a comprehensive base of knowledge for future RCTs. PMID:24686105

An evaluation of the effectiveness of recruitment methods: the staying well after depression randomized controlled trial.

PubMed

Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J Mark G

2014-04-01

Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties in recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited, and trials often fail to report sufficient details about the recruitment sources and resources utilized. We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. We describe eight recruitment methods utilized and two further sources not initiated by the research team and examine their efficacy in terms of (1) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial; (2) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants; and (3) comparison of sociodemographic characteristics of individuals recruited from different sources. Poster advertising, web-based advertising, and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters, and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in other geographical locations. Recruitment source was unavailable for participants who could not be reached after the initial contact. Thus, it is possible that the efficiency of certain methods of recruitment was poorer than estimated. Efficacy and costs of other recruitment initiatives, such as providing travel expenses to the in-person eligibility assessment and making follow-up telephone calls to candidates who contacted the recruitment team but could not be screened promptly, were not analysed. Website advertising resulted in the highest number of randomized participants and was the second cheapest method of recruiting. Future research should evaluate the effectiveness of recruitment strategies for other samples to contribute to a comprehensive base of knowledge for future RCTs.

Evaluation and validation of social and psychological markers in randomised trials of complex interventions in mental health: a methodological research programme.

PubMed

Dunn, Graham; Emsley, Richard; Liu, Hanhua; Landau, Sabine; Green, Jonathan; White, Ian; Pickles, Andrew

2015-11-01

The development of the capability and capacity to evaluate the outcomes of trials of complex interventions is a key priority of the National Institute for Health Research (NIHR) and the Medical Research Council (MRC). The evaluation of complex treatment programmes for mental illness (e.g. cognitive-behavioural therapy for depression or psychosis) not only is a vital component of this research in its own right but also provides a well-established model for the evaluation of complex interventions in other clinical areas. In the context of efficacy and mechanism evaluation (EME) there is a particular need for robust methods for making valid causal inference in explanatory analyses of the mechanisms of treatment-induced change in clinical outcomes in randomised clinical trials. The key objective was to produce statistical methods to enable trial investigators to make valid causal inferences about the mechanisms of treatment-induced change in these clinical outcomes. The primary objective of this report is to disseminate this methodology, aiming specifically at trial practitioners. The three components of the research were (1) the extension of instrumental variable (IV) methods to latent growth curve models and growth mixture models for repeated-measures data; (2) the development of designs and regression methods for parallel trials; and (3) the evaluation of the sensitivity/robustness of findings to the assumptions necessary for model identifiability. We illustrate our methods with applications from psychological and psychosocial intervention trials, keeping the technical details to a minimum, leaving the reporting of the more theoretical and mathematically demanding results for publication in appropriate specialist journals. We show how to estimate treatment effects and introduce methods for EME. We explain the use of IV methods and principal stratification to evaluate the role of putative treatment effect mediators and therapeutic process measures. These results are extended to the analysis of longitudinal data structures. We consider the design of EME trials. We focus on designs to create convincing IVs, bearing in mind assumptions needed to attain model identifiability. A key area of application that has become apparent during this work is the potential role of treatment moderators (predictive markers) in the evaluation of treatment effect mechanisms for personalised therapies (stratified medicine). We consider the role of targeted therapies and multiarm trials and the use of parallel trials to help elucidate the evaluation of mediators working in parallel. In order to demonstrate both efficacy and mechanism, it is necessary to (1) demonstrate a treatment effect on the primary (clinical) outcome, (2) demonstrate a treatment effect on the putative mediator (mechanism) and (3) demonstrate a causal effect from the mediator to the outcome. Appropriate regression models should be applied for (3) or alternative IV procedures, which account for unmeasured confounding, provided that a valid instrument can be identified. Stratified medicine may provide a setting where such instruments can be designed into the trial. This work could be extended by considering improved trial designs, sample size considerations and measurement properties. The project presents independent research funded under the MRC-NIHR Methodology Research Programme (grant reference G0900678).

Phase II Trial of Sorafenib in Combination with Carboplatin and Paclitaxel in Patients with Metastatic Uveal Melanoma: SWOG S0512

PubMed Central

Bhatia, Shailender; Moon, James; Margolin, Kim A.; Weber, Jeffrey S.; Lao, Christopher D.; Othus, Megan; Aparicio, Ana M.; Ribas, Antoni; Sondak, Vernon K.

2012-01-01

Background Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP) in metastatic uveal melanoma. Methods Twenty-five patients with stage IV uveal melanoma who had received 0–1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6) and paclitaxel (225 mg/m2) administered IV on day 1 plus sorafenib (400 mg PO twice daily), followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR); a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). Results No confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0–14%]) and the study was terminated at the first stage. Minor responses (tumor regression less than 30%) were seen in eleven of 24 (45%) patients. The median PFS was 4 months [95% CI: 1–6 months] and the 6-month PFS was 29% [95% CI: 13%–48%]. The median OS was 11 months [95% CI: 7–14 months]. Conclusion In this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients. Trial Registration ClinicalTrials.gov NCT00329641 PMID:23226204

Efficacy of respiratory muscle training in weaning of mechanical ventilation in patients with mechanical ventilation for 48hours or more: A Randomized Controlled Clinical Trial.

PubMed

Sandoval Moreno, L M; Casas Quiroga, I C; Wilches Luna, E C; García, A F

2018-02-02

To evaluate the efficacy of respiratory muscular training in the weaning of mechanical ventilation and respiratory muscle strength in patients on mechanical ventilation of 48hours or more. Randomized controlled trial of parallel groups, double-blind. Ambit: Intensive Care Unit of a IV level clinic in the city of Cali. 126 patients in mechanical ventilation for 48hours or more. The experimental group received daily a respiratory muscle training program with treshold, adjusted to 50% of maximal inspiratory pressure, additional to standard care, conventional received standard care of respiratory physiotherapy. MAIN INTEREST VARIABLES: weaning of mechanical ventilation. Other variables evaluated: respiratory muscle strength, requirement of non-invasive mechanical ventilation and frequency of reintubation. intention-to-treat analysis was performed with all variables evaluated and analysis stratified by sepsis condition. There were no statistically significant differences in the median weaning time of the MV between the groups or in the probability of extubation between groups (HR: 0.82 95% CI: 0.55-1.20 P=.29). The maximum inspiratory pressure was increased in the experimental group on average 9.43 (17.48) cmsH20 and in the conventional 5.92 (11.90) cmsH20 (P=.48). The difference between the means of change in maximal inspiratory pressure was 0.46 (P=.83 95%CI -3.85 to -4.78). respiratory muscle training did not demonstrate efficacy in the reduction of the weaning period of mechanical ventilation nor in the increase of respiratory muscle strength in the study population. Registered study at ClinicalTrials.gov (NCT02469064). Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial.

PubMed

Elewski, Boni E; Okun, Martin M; Papp, Kim; Baker, Christopher S; Crowley, Jeffrey J; Guillet, Gérard; Sundaram, Murali; Poulin, Yves; Gu, Yihua; Geng, Ziqian; Williams, David A; Rich, Phoebe A

2018-01-01

Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point. This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis. Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis). Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P < .001]) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%. Patients with less than 5% BSA involvement were not eligible for enrollment. After 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A systematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine efficacy.

PubMed

Patel, Manish; Glass, Roger I; Jiang, Baoming; Santosham, Mathuram; Lopman, Ben; Parashar, Umesh

2013-07-15

Identifying an immunological correlate of protection for rotavirus vaccines (Rotarix [RV1] and RotaTeq [RV5]) would substantially facilitate testing of interventions for improving efficacy in developing countries and evaluating additional candidate rotavirus vaccines. We accessed PubMed and ClinicalTrials.gov to identify immunogenicity and efficacy trials for RV1 and RV5 to correlate anti-rotavirus serum immunoglobulin A (IgA) antibody titers vs efficacy in regions stratified by all-cause under-5 mortality rates (u5MR). We established a cutoff point for IgA geometric mean concentration or titer (GMC) that predicted lower efficacy and calculated pooled vaccine efficacy among countries with high vs low IgA titers. We observed an inverse correlation between u5MR and IgA titers for RV1 (r(2) = 0.72; P < .001 and RV5 (r(2) = 0.66; P < .001) and between efficacy and IgA titers for both vaccines (r(2) = 0.56; P = .005). Postimmunization anti-rotavirus IgA GMC <90 were associated with decline in vaccine efficacy. Efficacy during first 2 years of life was significantly lower among countries with IgA GMC < 90 (44%; 95% confidence interval [CI], 30-55) compared to countries with GMC > 90 (85%; 95% CI, 82-88). We observed a significant correlation between IgA titers and rotavirus vaccine efficacy and hypothesize that a critical level of IgA antibody titer is associated with a sufficient level of sustained protection after rotavirus vaccination.

Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial.

PubMed

Wheeler, Cosette M; Castellsagué, Xavier; Garland, Suzanne M; Szarewski, Anne; Paavonen, Jorma; Naud, Paulo; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Kitchener, Henry; Teixeira, Júlio C; Skinner, S Rachel; Jaisamrarn, Unnop; Limson, Genara; Romanowski, Barbara; Aoki, Fred Y; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; Harper, Diane M; Huh, Warner; Hardt, Karin; Zahaf, Toufik; Descamps, Dominique; Struyf, Frank; Dubin, Gary; Lehtinen, Matti

2012-01-01

We evaluated the efficacy of the human papillomavirus HPV-16/18 AS04-adjuvanted vaccine against non-vaccine oncogenic HPV types in the end-of-study analysis after 4 years of follow-up in PATRICIA (PApilloma TRIal against Cancer In young Adults). Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to HPV-16/18 vaccine or a control hepatitis A vaccine, via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The study was double-blind. The primary endpoint of PATRICIA has been reported previously; the present analysis evaluates cross-protective vaccine efficacy against non-vaccine oncogenic HPV types in the end-of-study analysis. Analyses were done for three cohorts: the according-to-protocol cohort for efficacy (ATP-E; vaccine n=8067, control n=8047), total vaccinated HPV-naive cohort (TVC-naive; no evidence of infection with 14 oncogenic HPV types at baseline, approximating young adolescents before sexual debut; vaccine n=5824, control n=5820), and the total vaccinated cohort (TVC; all women who received at least one vaccine dose, approximating catch-up populations that include sexually active women; vaccine n=9319, control=9325). Vaccine efficacy was evaluated against 6-month persistent infection, cervical intraepithelial neoplasia grade 2 or greater (CIN2+) associated with 12 non-vaccine HPV types (individually or as composite endpoints), and CIN3+ associated with the composite of 12 non-vaccine HPV types. This study is registered with ClinicalTrials.gov, number NCT00122681. Consistent vaccine efficacy against persistent infection and CIN2+ (with or without HPV-16/18 co-infection) was seen across cohorts for HPV-33, HPV-31, HPV-45, and HPV-51. In the most conservative analysis of vaccine efficacy against CIN2+, where all cases co-infected with HPV-16/18 were removed, vaccine efficacy was noted for HPV-33 in all cohorts, and for HPV-31 in the ATP-E and TVC-naive. Vaccine efficacy against CIN2+ associated with the composite of 12 non-vaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), with or without HPV-16/18 co-infection, was 46·8% (95% CI 30·7-59·4) in the ATP-E, 56·2% (37·2-69·9) in the TVC-naive, and 34·2% (20·4-45·8) in the TVC. Corresponding values for CIN3+ were 73·8% (48·3-87·9), 91·4% (65·0-99·0), and 47·5% (22·8-64·8). Data from the end-of-study analysis of PATRICIA show cross-protective efficacy of the HPV-16/18 vaccine against four oncogenic non-vaccine HPV types-HPV-33, HPV-31, HPV-45, and HPV-51-in different trial cohorts representing diverse groups of women. GlaxoSmithKline Biologicals. Copyright © 2012 Elsevier Ltd. All rights reserved.

New treatment directions for IPF: current status of ongoing and upcoming clinical trials.

PubMed

Macagno, Francesco; Varone, Francesco; Leone, Paolo Maria; Mari, Pier-Valerio; Panico, Loredana; Berardini, Ludovica; Richeldi, Luca

2017-07-01

The main objective of this review is to explore the wide and expanding field of new clinical trials in IPF. Recent trials have confirmed the efficacy of the approved drugs pirfenidone and nintedanib; nonetheless, the discovery of new biological pathways has opened new horizons in this field. Areas covered: New strategies against matrix deposition are under study and so is for the role of immunity and autoimmunity. Recent advances in the use of stem cells are opening new possibilities for the recovery of damaged lung tissues. The role of microbioma is under investigation in order to evaluate the use of antibiotics in IPF treatment. Analysing all the new and the upcoming clinical trials, we are trying to offer a comprehensive view of the emerging new frontiers in the treatment of IPF. Expert commentary: The key points for the ongoing and upcoming clinical trials will be to avoid previous mistakes and to choose carefully both study populations and efficacy endpoints. The exciting possibility to enrol patients with progressive lung fibrosis, both idiopathic and not, could be a next step forward. How the existing therapies will fit in a futurist scenario of personalized medicine is still a challenge.

The Utility of Low-Dose Aripiprazole for the Treatment of Bipolar II and Bipolar NOS Depression.

PubMed

Kelly, Tammas; Lieberman, Daniel Z

2017-02-01

Despite initial reports of efficacy in bipolar depression, multicenter trials did not show aripiprazole to be better than placebo, possibly because the doses used were too high, leading to lower efficacy and high dropout rates. This study evaluated the effects of low-dose aripiprazole. Extensive clinical experience has suggested that doses beyond 5 mg are rarely efficacious. Data were gathered from patients with bipolar II or bipolar not otherwise specified depression using a retrospective chart review. Efficacy was assessed with the Clinical Global Impression-Improvement score. Patients who had at least 2 trials of aripiprazole were included in a retrospective off-on-off-on experimental design. All patients were on other medications when aripiprazole was started. Patients were treated with doses of 1 to 5 mg. On average, patients were rated improved or very much improved compared with baseline. Sixteen of 211 patients worsened or experienced no change. Forty-four patients (21%) discontinued due to adverse effects. The group of patients who underwent off-on-off-on trials experienced statistically significant improvement when they started and restarted aripiprazole, and statistically significant worsening when they discontinued it. When treating bipolar II or bipolar not otherwise specified depression, low doses of aripiprazole, 5 mg or less, may be more effective and better tolerated than higher ones. Clinicians should start treatment with a very low dose and give patients time to respond.

A realist evaluation of patients’ decisions to deprescribe in the EMPOWER trial

PubMed Central

Martin, Philippe; Tannenbaum, Cara

2017-01-01

Background and objectives Successful mechanisms for engaging patients in the deprescribing process remain unknown but may include: (1) triggering motivation to deprescribe by increasing patients’ knowledge and concern about medications; (2) building capacity to taper by augmenting self-efficacy and (3) creating opportunities to discuss and receive support for deprescribing from a healthcare provider. We tested these mechanisms during theEliminating Medications through Patient Ownership of End Results (EMPOWER) () trial and investigated the contexts that led to positive and negative deprescribing outcomes. Design A realist evaluation using a sequential mixed methods approach, conducted alongside the EMPOWER randomised clinical trial. Setting Community, Quebec, Canada. Participants 261 older chronic benzodiazepine consumers, who received the EMPOWER intervention and had complete 6-month follow-up data. Intervention Mailed deprescribing brochure on benzodiazepines. Measurements Motivation (intent to discuss deprescribing; change in knowledge test score; change in beliefs about the risk–benefits of benzodiazepines, measured with the Beliefs about Medicines Questionnaire), capacity (self-efficacy for tapering) and opportunity (support from a physician or pharmacist). Results The intervention triggered the motivation to deprescribe among 167 (n=64%) participants (mean age 74.6 years±6.3, 72% women), demonstrated by improved knowledge (risk difference, 58.50% (95% CI 46.98% to 67.44%)) and increased concern about taking benzodiazepines (risk difference, 67.67% (95% CI 57.36% to 74.91%)). Those who attempted to taper exhibited increased self-efficacy (risk difference, 56.90% (95% CI 45.41% to 65.77%)). Contexts where the deprescribing mechanisms failed included lack of support from a healthcare provider, a focus on short-term quality of life, intolerance to withdrawal symptoms and perceived poor health. Conclusion Deprescribing mechanisms that target patient motivation and capacity to deprescribe yield successful outcomes in contexts where healthcare providers are supportive, and patients do not have internal competing desires to remain on drug therapy. Trial registration number ClinicalTrials.gov: NCT01148186. PMID:28473524

Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction).

PubMed

Sanz-Ruiz, Ricardo; Casado Plasencia, Ana; Borlado, Luis R; Fernández-Santos, María Eugenia; Al-Daccak, Reem; Claus, Piet; Palacios, Itziar; Sádaba, Rafael; Charron, Dominique; Bogaert, Jan; Mulet, Miguel; Yotti, Raquel; Gilaberte, Immaculada; Bernad, Antonio; Bermejo, Javier; Janssens, Stefan; Fernández-Avilés, Franciso

2017-06-23

Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398. © 2017 American Heart Association, Inc.

Skin antiseptics in venous puncture site disinfection for preventing blood culture contamination: A Bayesian network meta-analysis of randomized controlled trials.

PubMed

Liu, Wenjie; Duan, Yuchen; Cui, Wenyao; Li, Li; Wang, Xia; Dai, Heling; You, Chao; Chen, Maojun

2016-07-01

To compare the efficacy of several antiseptics in decreasing the blood culture contamination rate. Network meta-analysis. Electronic searches of PubMed and Embase were conducted up to November 2015. Only randomized controlled trials or quasi-randomized controlled trials were eligible. We applied no language restriction. A comprehensive review of articles in the reference lists was also accomplished for possible relevant studies. Relevant studies evaluating efficacy of different antiseptics in venous puncture site for decreasing the blood culture contamination rate were included. The data were extracted from the included randomized controlled trials by two authors independently. The risk of bias was evaluated using Detsky scale by two authors independently. We used WinBUGS1.43 software and statistic model described by Chaimani to perform this network meta-analysis. Then graphs of statistical results of WinBUGS1.43 software were generated using 'networkplot', 'ifplot', 'netfunnel' and 'sucra' procedure by STATA13.0. Odds ratio and 95% confidence intervals were assessed for dichotomous data. A probability of p less than 0.05 was considered to be statistically significant. Compared with ordinary meta-analyses, this network meta-analysis offered hierarchies for the efficacy of different antiseptics in decreasing the blood culture contamination rate. Seven randomized controlled trials involving 34,408 blood samples were eligible for the meta-analysis. No significant difference was found in blood culture contamination rate among different antiseptics. No significant difference was found between non-alcoholic antiseptics and alcoholic antiseptics, alcoholic chlorhexidine and povidone iodine, chlorhexidine and iodine compounds, povidone iodine and iodine tincture in this aspect, respectively. Different antiseptics may not affect the blood culture contamination rate. Different intervals between the skin disinfection and the venous puncture, the different settings (emergency room, medical wards, and intensive care units) and the performance of the phlebotomy may affect the blood culture contamination rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is laser acupuncture an effective complementary therapy for obesity management? A systematic review of clinical trials.

PubMed

Namazi, Nazli; Khodamoradi, Kajal; Larijani, Bagher; Ayati, Mohammad Hossein

2017-12-01

Complementary therapies may increase the success rate of weight loss via a calorie-restricted diet. Acupuncture is a popular complementary therapy for obesity management. To our knowledge, no studies have summarised the effects of laser acupuncture (LA) on obesity. To evaluate the efficacy of LA, in particular with respect to its impact on anthropometric features and appetite in obese adults, by conducting a systematic review of previous clinical trials. We searched PubMed/Medline, Scopus, Web of Science, the Cochrane Library, Embase and Google Scholar electronic databases for papers published through October 2016. All clinical trials in English containing either anthropometric indices or appetite parameters were included. Two reviewers independently examined studies based on a predefined form for data extraction and the Jadad scale for quality assessment in order to minimise bias throughout the evaluation. After screening the papers, seven clinical trials met the criteria and were included in the systematic review. Positive effects of LA therapy were seen in body weight (n=3), body mass index (n=5), waist circumference (n=4), hip circumference (n=3), waist to hip ratio (n=4) and % fat mass (n=3). Appetite parameters were reported in one study, which showed that LA can reduce appetite and increase the sensation of feeling full. Although some studies have indicated beneficial effects for LA on obesity, the lack of evidence with high methodological quality made it impossible to reach a definitive conclusion about the efficacy of LA for obesity management. Further high-quality, randomised, sham-controlled clinical trials with a larger sample size are needed to shed light on the efficacy of LA for obesity management and weight maintenance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

8-Way Randomized Controlled Trial of Doxylamine, Pyridoxine and Dicyclomine for Nausea and Vomiting during Pregnancy: Restoration of Unpublished Information.

PubMed

Zhang, Rujun; Persaud, Navindra

2017-01-01

We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published. Double blinded, multi-centred, randomized placebo-controlled study. 14 clinics in the United States. 2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled. Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights. Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians. Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were "evaluated moderate or excellent" was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity. The available information about this "8-way Bendectin" trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias. Not registered.

Effects of Self-Evaluated Value and Cognition on Leisure Science Engagement

ERIC Educational Resources Information Center

Jack, Brady Michael; She, Hsiao-Ching; Lin, Huann-shyang

2016-01-01

This study uses the Taiwan Programme for International Student Assessment (PISA) 2006 Main Survey and Taiwan PISA 2015 Field Trial survey datasets to investigate how self-evaluated values (i.e. personal and general) and cognitive factors (i.e. self-efficacy and self-concept) of two groups of Taiwanese 15-year-old students separated by 8 years of…

Evaluation of imidacloprid-treated traps as an attract and kill system for filth flies during contingency operations.

USDA-ARS?s Scientific Manuscript database

Field trials were conducted to evaluate if filth fly trap efficacy was increased by application of an insecticide to a trap’s exterior. Four Fly Terminator® Pro traps baited with Fly Terminator® attractant were suspended on PVC pipe framing at a Florida waste transfer site. Exterior surfaces of tw...

Evaluation of buparvaquone (BUTA-Kel KELA, Belgium) as a treatment of East Coast fever in cattle, in the peri-urban of Dar Es Salaam city, Tanzania.

PubMed

Mbwambo, H A; Magwisha, H B; Mfinanga, J M

2006-06-30

Evaluation trials of the efficacy of buparvaquone (BUTA-kel KELA Laboratoria, N.V. Belgium), as a treatment of field cases of Theileria parva infection (East Coast fever - ECF) were carried out on 63 cattle in the peri-urban of Dar Es Salaam city, Tanzania, during the period November 2004 to August 2005. Thirty-two cattle (56%) received single-dose treatment (2.5 mg buparvaquone per kg body weight), while two and three-dose treatment with interval(s) of 48 h was given to 33% and 11% of total treated cattle, respectively; 38 cattle (60.3%) were treated at an early stage of the disease, while 25 cattle (39.7%) were treated at an advanced stage of the disease. The rectal body temperature of 90.5% of buparvaquone-treated cattle dropped to normal values (37.5-39.5 degrees C) by day 7 of treatment, and by day 15 of treatment 96.8% of treated cattle showed normal values. Pulmonary signs were observed in 8/68 (11.8%) of total ECF diagnosed cattle and were successfully treated, albeit with parvaquone plus frusemide (Fruvexon); were not included in final evaluation of the efficacy of BUTA-kel. The present evaluation trials record a recovery rate of 95.2%. Buparvaquone (BUTA-kel KELA Laboratoria, N.V. Belgium), therefore, records another efficacious and valuable alternative treatment against East Coast fever in Tanzania.

Using Small-Scale Randomized Controlled Trials to Evaluate the Efficacy of New Curricular Materials

PubMed Central

Bass, Kristin M.; Stark, Louisa A.

2014-01-01

How can researchers in K–12 contexts stay true to the principles of rigorous evaluation designs within the constraints of classroom settings and limited funding? This paper explores this question by presenting a small-scale randomized controlled trial (RCT) designed to test the efficacy of curricular supplemental materials on epigenetics. The researchers asked whether the curricular materials improved students’ understanding of the content more than an alternative set of activities. The field test was conducted in a diverse public high school setting with 145 students who were randomly assigned to a treatment or comparison condition. Findings indicate that students in the treatment condition scored significantly higher on the posttest than did students in the comparison group (effect size: Cohen's d = 0.40). The paper discusses the strengths and limitations of the RCT, the contextual factors that influenced its enactment, and recommendations for others wishing to conduct small-scale rigorous evaluations in educational settings. Our intention is for this paper to serve as a case study for university science faculty members who wish to employ scientifically rigorous evaluations in K–12 settings while limiting the scope and budget of their work. PMID:25452482

Need for common internal controls when assessing the relative efficacy of pharmacologic agents using a meta-analytic approach: case study of cyclooxygenase 2-selective inhibitors for the treatment of osteoarthritis.

PubMed

Lee, Chin; Hunsche, Elke; Balshaw, Robert; Kong, Sheldon X; Schnitzer, Thomas J

2005-08-15

To evaluate the role of common internal controls in a meta-analysis of the relative efficacy of cyclooxygenase 2-selective inhibitors (coxibs) in the treatment of osteoarthritis (OA). A systematic search of Medline and US Food and Drug Administration electronic databases was performed to identify randomized, placebo-controlled clinical trials of coxibs (etoricoxib, celecoxib, rofecoxib, valdecoxib) in patients with hip and/or knee OA. The effect size for coxibs and common active internal controls (nonsteroidal antiinflammatory drugs [NSAIDs], naproxen) were determined by the mean changes from baseline in Western Ontario and McMaster Universities Osteoarthritis Index pain subscores as compared with placebo. The effect size for all coxib groups combined (0.44) indicated greater efficacy as compared with placebo, but significant heterogeneity (P < 0.0001) was observed. Rofecoxib at dosages of 12.5 mg/day and 25 mg/day and etoricoxib at a dosage of 60 mg/day had similar effect sizes (0.68 and 0.73, respectively), but these effect sizes were comparatively greater than those for both celecoxib at dosages of 200 mg/day and 100 mg twice daily or valdecoxib at a dosage of 10 mg/day (0.26 and 0.16, respectively). The effect sizes for NSAIDs or naproxen versus placebo, as determined using data from rofecoxib/etoricoxib trials, were consistently higher than the effect sizes derived from trials of celecoxib/valdecoxib. Significant heterogeneity was present in the overall effect size for NSAIDs (P = 0.007) and naproxen (P = 0.04) groups based on data available from all coxib trials. Coxibs and common active internal controls showed larger effect sizes versus placebo in the rofecoxib/etoricoxib trials than in the celecoxib/valdecoxib trials. These findings suggest systematic differences among published coxib trials and emphasize the need for direct-comparison trials. In the absence of such trials, common internal controls should be assessed when performing indirect meta-analytic comparisons.

Vaccine approaches to malaria control and elimination: Insights from mathematical models.

PubMed

White, Michael T; Verity, Robert; Churcher, Thomas S; Ghani, Azra C

2015-12-22

A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts. Several candidate vaccines targeting different stages of the malaria parasite's lifecycle are currently under development, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection, having recently completed Phase III trials. Predicting the public health impact of a candidate malaria vaccine requires using clinical trial data to estimate the vaccine's efficacy profile--the initial efficacy following vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacy profile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematical models. Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocytic vaccines and transmission-blocking vaccines from clinical trial data. In the case of RTS,S/AS01, model estimates from Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection, with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waning over the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II or Phase III clinical trials so we review ongoing work investigating how a clinical trial might be designed to ensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstrate how parameters estimated from clinical trials can be used to predict the impact of vaccination campaigns on malaria using a mathematical model of malaria transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

The efficacy of a behavioral activation intervention among depressed US Latinos with limited English language proficiency: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Major depressive disorder is highly prevalent among Latinos with limited English language proficiency in the United States. Although major depressive disorder is highly treatable, barriers to depression treatment have historically prevented Latinos with limited English language proficiency from accessing effective interventions. The project seeks to evaluate the efficacy of behavioral activation treatment for depression, an empirically supported treatment for depression, as an intervention that may address some of the disparities surrounding the receipt of efficacious mental health care for this population. Methods/design Following a pilot study of behavioral activation treatment for depression with 10 participants which yielded very promising results, the current study is a randomized control trial testing behavioral activation treatment for depression versus a supportive counseling treatment for depression. We are in the process of recruiting 60 Latinos with limited English language proficiency meeting criteria for major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th and 5th Edition for participation in a single-center efficacy trial. Participants are randomized to receive 10 sessions of behavioral activation treatment for depression (n = 30) or 10 sessions of supportive counseling (n = 30). Assessments occur prior to each session and at 1 month after completing treatment. Intervention targets include depressive symptomatology and the proposed mechanisms of behavioral activation treatment for depression: activity level and environmental reward. We will also examine other factors related to treatment outcome such as treatment adherence, treatment satisfaction, and therapeutic alliance. Discussion This randomized controlled trial will allow us to determine the efficacy of behavioral activation treatment for depression in a fast-growing, yet highly underserved population in US mental health services. The study is also among the first to examine the effect of the proposed mechanisms of change of behavioral activation treatment for depression (that is, activity level and environmental reward) on depression over time. To our knowledge, this is the first randomized controlled trial to compare an empirical-supported treatment to a control supportive counseling condition in a sample of depressed, Spanish-speaking Latinos in the United States. Trial registration Clinical Trials Register: NCT01958840; registered 8 October 2013. PMID:24938081

Efficacy of individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP): study protocol for a randomized, double-dummy, double-blind, placebo-controlled trial

PubMed Central

2013-01-01

Background The perimenopausal period refers to the interval when women’s menstrual cycles become irregular and is characterized by an increased risk of depressive symptoms. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. Previous trials suggest that individualized homeopathic treatments improve depression. In classical homeopathy, an individually selected homeopathic remedy is prescribed after a complete case history of the patient. The aim of this study is to assess the efficacy and safety of the homeopathic individualized treatment versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. Methods/design A randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a six-week follow-up study was designed. The study will be conducted in a public research hospital in Mexico City (Juárez de México Hospital) in the outpatient service of homeopathy. One hundred eighty nine peri- and postmenopausal women diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (moderate to severe intensity) will be included. The primary outcome is change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression after the fourth and sixth week of treatment. Secondary outcomes are: Beck Depression Inventory change in mean score, Greene’s Scale change in mean score, response and remission rates and safety. Efficacy data will be analyzed in the intention-to-treat population. To determine differences in the primary and secondary outcomes among groups at baseline and weeks four and six, data will be analyzed by analysis of variance for independent measures with the Bonferroni post-hoc test. Discussion This study is the first trial of classical homeopathy that will evaluate the efficacy of homeopathic individualized treatment using C-potencies versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. It is an attempt to deal with the obstacles of homeopathic research due to the need for individual prescriptions in one of the most common psychiatric diseases. Trial registration ClinicalTrials.gov Identifier: NCT01635218. PMID:23782520

Differing antidepressant maintenance methodologies.

PubMed

Safer, Daniel J

2017-10-01

The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

Efficacy of a modified live Flavobacterium columnare vaccine in fish.

PubMed

Shoemaker, Craig A; Klesius, Phillip H; Drennan, John D; Evans, Joyce J

2011-01-01

Flavobacterium columnare is an aquatic bacterium that is responsible for columnaris disease. This aquatic pathogen has a worldwide distribution and is highly infectious to both warm and cold water fish. A modified live F. columnare vaccine was developed by repeated passage of a virulent strain on increasing concentrations of rifampicin that resulted in attenuation. Here we report vaccination/challenge trials to evaluate efficacy and safety. In separate laboratory trials, immersion vaccination of channel catfish (Ictalurus punctatus) fry between 10 to 48 days post hatch (DPH) with experimental vaccine or licensed product resulted in relative percent survival (RPS) between 57-94% following challenge. Similarly, a vaccination/challenge trial using largemouth bass (Micropterus salmoides) fry at 10 DPH was performed using various doses of licensed product under laboratory conditions. Results demonstrated safety of the vaccine and significant protection following challenge with RPS values between 74-94%, depending on vaccine dose. Together, these trials demonstrate the vaccine administered to early life-stage channel catfish and largemouth bass is safe and reduces mortality following challenge with F. columnare. Published by Elsevier Ltd.

Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer.

PubMed

Lousberg, Laurence; Jerusalem, Guy

2016-01-01

Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus-exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile.

Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer

PubMed Central

Lousberg, Laurence; Jerusalem, Guy

2016-01-01

Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus–exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile. PMID:28096680

Effective Obesity Treatments

ERIC Educational Resources Information Center

Powell, Lynda H.; Calvin, James E., III; Calvin, James E., Jr.

2007-01-01

To curb the epidemic of obesity in the United States, revised Medicare policy allows support for efficacious obesity treatments. This review summarizes the evidence from rigorous randomized trials (9 lifestyle trials, 5 drug trials, and 2 surgical trials) on the efficacy and risk-benefit profile of lifestyle, drug, and surgical interventions aimed…

Tenofovir-based Pre-Exposure Prophylaxis for HIV Prevention: Evidence and evolving questions

PubMed Central

Celum, Connie; Baeten, Jared

2012-01-01

Purpose of review Topical tenofovir gel and oral tenofovir and emtricitabine/tenofovir (FTC/TDF) have been demonstrated to have efficacy in preventing HIV-1 in some populations. Pre-exposure prophylaxis (PrEP) trials and future directions are summarized. Recent findings Peri-coital use of 1% tenofovir gel in CAPRISA 004 reduced HIV-1 acquisition by 39% and HSV-2 acquisition by 51%. Daily oral FTC/TDF demonstrated 44% reduction in HIV-1 acquisition among men who have sex with men (MSM) in iPrEx. Both studies showed higher efficacy among those with higher adherence. Efficacy of daily oral TDF and FTC/TDF was 66% and 73%, respectively, among HIV-1 uninfected partners in an HIV-1 serodiscordant partnership in the Partners PrEP Study. Efficacy of daily oral FTC/TDF was 66% in young heterosexuals in Botswana in the TDF-2 trial. The FEM-PrEP and VOICE studies in African women found no efficacy with oral FTC/TDF and TDF, respectively. Safety and tolerability were excellent and limited resistance was observed in seroconverters. Summary Topical tenofovir gel showed efficacy in African women and daily oral TDF and FTC/TDF were efficacious in MSM, and African HIV-1 serodiscordant couples and young heterosexuals. The reasons for lack of efficacy of oral FTC/TDF and TDF in two studies in African women are being investigated. Longer-acting formulations, invtravaginal rings, and new candidate antiretrovirals are being evaluated. PMID:22156901

Balance training with multi-task exercises improves fall-related self-efficacy, gait, balance performance and physical function in older adults with osteoporosis: a randomized controlled trial.

PubMed

Halvarsson, Alexandra; Franzén, Erika; Ståhle, Agneta

2015-04-01

To evaluate the effects of a balance training program including dual- and multi-task exercises on fall-related self-efficacy, fear of falling, gait and balance performance, and physical function in older adults with osteoporosis with an increased risk of falling and to evaluate whether additional physical activity would further improve the effects. Randomized controlled trial, including three groups: two intervention groups (Training, or Training+Physical activity) and one Control group, with a 12-week follow-up. Stockholm County, Sweden. Ninety-six older adults, aged 66-87, with verified osteoporosis. A specific and progressive balance training program including dual- and multi-task three times/week for 12 weeks, and physical activity for 30 minutes, three times/week. Fall-related self-efficacy (Falls Efficacy Scale-International), fear of falling (single-item question - 'In general, are you afraid of falling?'), gait speed with and without a cognitive dual-task at preferred pace and fast walking (GAITRite®), balance performance tests (one-leg stance, and modified figure of eight), and physical function (Late-Life Function and Disability Instrument). Both intervention groups significantly improved their fall-related self-efficacy as compared to the controls (p ≤ 0.034, 4 points) and improved their balance performance. Significant differences over time and between groups in favour of the intervention groups were found for walking speed with a dual-task (p=0.003), at fast walking speed (p=0.008), and for advanced lower extremity physical function (p=0.034). This balance training program, including dual- and multi-task, improves fall-related self-efficacy, gait speed, balance performance, and physical function in older adults with osteoporosis. © The Author(s) 2014.

A Systems Approach to Designing Effective Clinical Trials Using Simulations

PubMed Central

Fusaro, Vincent A.; Patil, Prasad; Chi, Chih-Lin; Contant, Charles F.; Tonellato, Peter J.

2013-01-01

Background Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit compared to standard clinical therapy. This study demonstrates a computational framework to systematically evaluate pre-clinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and non-genetic clinical-based, multiple dose adjustment protocols, pharmacokinetic/pharmacodynamics (PK/PD) modeling and international normalization ratio (INR) prediction, as well as various types of outcome measures. We validated the framework by conducting 1,000 simulations of the CoumaGen clinical trial primary endpoints. The simulation predicted a mean time in therapeutic range (TTR) of 70.6% and 72.2% (P = 0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in TTR between the pharmacogenetic and standard arm (78.8% vs. 73.8%; P = 0.0065), respectively. Conclusions We demonstrate that this simulation framework is useful in the pre-clinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk. PMID:23261867

Randomised Clinical Efficacy Trial of Topiramate and Nitrazepam in Treatment of Infantile Spasms

PubMed Central

FALLAH, Razieh; SALOR, Fahimah; AKHAVAN KARBASI, Sedighah; MOTAGHIPISHEH, Hadi

2014-01-01

Objective Infantile spasms (IS) are among the most catastrophic epileptic syndromes of infancy. The purpose of this study was to compare efficacy and safety of topiramate (TPM) and nitrazepam (NZP) as first-line drugs in the treatment of IS. Materials & Methods In a parallel single-blinded randomized clinical trial, 50 patients with IS referred to Pediatric Neurology Clinic of Shahid Sadoughi University of Medical Sciences, Yazd, Iran, were evaluated from September 2008 to March 2010. Patients were randomly assigned to two groups to be treated with TPM or with NZP for 6 months. The primary endpoint was efficacy in cessation of all spasms or reduction of more than 50% in weekly seizure frequency, which was evaluated before and 6 months after the drug use. Secondary outcome was clinical sideeffects of the drugs. Results Twenty boys (40%) and 30 girls (60%) with the mean age of 9.4±3.8 months were evaluated. Cessation of all spasms occurred in 12 (48%) infants in TPM group and 4(16%) in NZP group. Eight (32%) children in TPM group and 7 (28%) in NZP group had more than 50% reduction in spasms frequency. So, TPM was more effective. Side effects were seen in 32% of TPM and in 36% of NZP groups. Conclusion Topiramate is an effective and safe drug, which might be considered as the firstline drug for the treatment of ISs. PMID:24665322

The effects of self-efficacy enhancing program on foot self-care behaviour of older adults with diabetes: A randomised controlled trial in elderly care facility, Peninsular Malaysia.

PubMed

Ahmad Sharoni, Siti Khuzaimah; Abdul Rahman, Hejar; Minhat, Halimatus Sakdiah; Shariff-Ghazali, Sazlina; Azman Ong, Mohd Hanafi

2018-01-01

Self-care behaviour is essential in preventing diabetes foot problems. This study aimed to evaluate the effectiveness of health education programs based on the self-efficacy theory on foot self-care behaviour for older adults with diabetes. A randomised controlled trial was conducted for 12 weeks among older adults with diabetes in elderly care facility in Peninsular Malaysia. Six elderly care facility were randomly allocated by an independent person into two groups (intervention and control). The intervention group (three elderly care facility) received a health education program on foot self-care behaviour while the control group (three elderly care facility) received standard care. Participants were assessed at baseline, and at week-4 and week-12 follow-ups. The primary outcome was foot-self-care behaviour. Foot care self-efficacy (efficacy expectation), foot care outcome expectation, knowledge of foot care and quality of life were the secondary outcomes. Data were analysed with Mixed Design Analysis of Variance using the Statistical Package for the Social Sciences version 22.0. 184 respondents were recruited but only 76 met the selection criteria and were included in the analysis. Foot self-care behaviour, foot care self-efficacy (efficacy expectation), foot care outcome expectation and knowledge of foot care improved in the intervention group compared to the control group (p < 0.05). However, some of these improvements did not significantly differ compared to the control group for QoL physical symptoms and QoL psychosocial functioning (p > 0.05). The self-efficacy enhancing program improved foot self-care behaviour with respect to the delivered program. It is expected that in the future, the self-efficacy theory can be incorporated into diabetes education to enhance foot self-care behaviour for elderly with diabetes living in other institutional care facilities. Australian New Zealand Clinical Trial Registry ACTRN12616000210471.

Medication adherence and tolerability of Alzheimer's disease medications: study protocol for a randomized controlled trial.

PubMed

Campbell, Noll L; Dexter, Paul; Perkins, Anthony J; Gao, Sujuan; Li, Lang; Skaar, Todd C; Frame, Amie; Hendrie, Hugh C; Callahan, Chris M; Boustani, Malaz A

2013-05-04

The class of acetylcholinesterase inhibitors (ChEI), including donepezil, rivastigmine, and galantamine, have similar efficacy profiles in patients with mild to moderate Alzheimer's disease (AD). However, few studies have evaluated adherence to these agents. We sought to prospectively capture the rates and reasons for nonadherence to ChEI and determine factors influencing tolerability and adherence. We designed a pragmatic randomized clinical trial to evaluate the adherence to ChEIs among older adults with AD. Participants include AD patients receiving care within memory care practices in the greater Indianapolis area. Participants will be followed at 6-week intervals up to 18 weeks to measure the primary outcome of ChEI discontinuation and adherence rates and secondary outcomes of behavioral and psychological symptoms of dementia. The primary outcome will be assessed through two methods, a telephone interview of an informal caregiver and electronic medical record data captured from each healthcare system through a regional health information exchange. The secondary outcome will be measured by the Healthy Aging Brain Care Monitor and the Neuropsychiatric Inventory. In addition, the trial will conduct an exploratory evaluation of the pharmacogenomic signatures for the efficacy and the adverse effect responses to ChEIs. We hypothesized that patient-specific factors, including pharmacogenomics and pharmacokinetic characteristics, may influence the study outcomes. This pragmatic trial will engage a diverse population from multiple memory care practices to evaluate the adherence to and tolerability of ChEIs in a real world setting. Engaging participants from multiple healthcare systems connected through a health information exchange will capture valuable clinical and non-clinical influences on the patterns of utilization and tolerability of a class of medications with a high rate of discontinuation. Clinicaltrials.gov: NCT01362686.

Efficacy of transcutaneous electrical nerve stimulation for rotator cuff tendinopathy: a systematic review.

PubMed

Desmeules, F; Boudreault, J; Roy, J S; Dionne, C E; Frémont, P; MacDermid, J C

2016-03-01

To perform a systematic review on the efficacy of transcutaneous electrical nerve stimulation (TENS) for the treatment of rotator cuff tendinopathy in adults. A literature search was conducted in four databases (CINAHL, Embase, PubMed and PeDRO) for randomised controlled trials published from date of inception until April 2015, comparing the efficacy of TENS for the treatment of rotator cuff tendinopathy with placebo or any other intervention. Risk of bias was evaluated using the Cochrane risk of bias tool. Results were summarised qualitatively. Six studies were included in this review. The mean methodological score was 49% (standard deviation 16%), indicating an overall high risk of bias. One placebo-controlled trial reported that a single TENS session provided immediate pain reduction for patients with rotator cuff tendinopathy, but did not follow the participants in the short, medium or long term. Two trials that compared ultrasound therapy with TENS reported discrepancy and contradictory results in terms of pain reduction and shoulder range of motion. Corticosteroid injections were found to be superior to TENS for pain reduction in the short term, but the differences were not clinically important. Other studies included in this review concluded that TENS was not superior to heat or pulsed radiofrequency. Due to the limited number of studies and the overall high risk of bias of the studies included in this review, no conclusions can be drawn on the efficacy of TENS for the treatment of rotator cuff tendinopathy. More methodologically sound studies are needed to document the efficacy of TENS. Until then, clinicians should prefer other evidence-based rehabilitation interventions proven to be efficacious to treat patients with rotator cuff tendinopathy. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

[A prospective multicenter randomized controlled clinical study on the efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution].

PubMed

Lu, Quan

2010-03-01

To evaluate efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution for the treatment of cough, expectoration, nasal congestion and runny nose in children. This was a prospective multicenter randomized single-blind, parallel-controlled clinical study. A total of 10 centers participated in this study, the actual number of cases in line with the program was 412, of whom 205 cases in trial group were treated with Guaifenesin compound pseudoephedrine hydrochloride oral solution, and 207 cases in control group with ambroxol hydrochloride oral solution, treatment of both groups persisted for 7 days. The improvement rate of each single symptom and the combined symptoms and the overall effective rate were compared between the two groups. The adverse drug reactions and compliance were assessed as well. The treatment of both groups showed efficacy. Except sputum stickiness, the improvement of all symptoms in trial group was superior to that in the control group on the 3rd day after treatment (P < 0.05) and except nasal congestion, the efficacy in all the other symptoms of trial group was better than that in the control group as well on the 7th day (P < 0.01). The improvement rate for combined symptoms of Guaifenesin compound pseudoephedrine hydrochloride oral solution was 82.9% and the overall efficacy rate was 89.3%. Guaifenesin compound Pseudoephedrine hydrochloride oral solution had higher compliance and its adverse event rate was merely 0.92%. Guaifenesin compound pseudoephedrine hydrochloride oral solution showed significant efficacy and safety in children for treatment of cough, expectoration, nasal congestion and runny nose caused by common cold or acute tracheobronchitis.

Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial.

PubMed

Holmes, David R; Kar, Saibal; Price, Matthew J; Whisenant, Brian; Sievert, Horst; Doshi, Shephal K; Huber, Kenneth; Reddy, Vivek Y

2014-07-08

In the PROTECT AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) trial that evaluated patients with nonvalvular atrial fibrillation (NVAF), left atrial appendage (LAA) occlusion was noninferior to warfarin for stroke prevention, but a periprocedural safety hazard was identified. The goal of this study was to assess the safety and efficacy of LAA occlusion for stroke prevention in patients with NVAF compared with long-term warfarin therapy. This randomized trial further assessed the efficacy and safety of the Watchman device. Patients with NVAF who had a CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and previous stroke/transient ischemic attack) score ≥2 or 1 and another risk factor were eligible. Patients were randomly assigned (in a 2:1 ratio) to undergo LAA occlusion and subsequent discontinuation of warfarin (intervention group, n = 269) or receive chronic warfarin therapy (control group, n = 138). Two efficacy and 1 safety coprimary endpoints were assessed. At 18 months, the rate of the first coprimary efficacy endpoint (composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death) was 0.064 in the device group versus 0.063 in the control group (rate ratio 1.07 [95% credible interval (CrI): 0.57 to 1.89]) and did not achieve the prespecified criteria noninferiority (upper boundary of 95% CrI ≥1.75). The rate for the second coprimary efficacy endpoint (stroke or SE >7 days' postrandomization) was 0.0253 versus 0.0200 (risk difference 0.0053 [95% CrI: -0.0190 to 0.0273]), achieving noninferiority. Early safety events occurred in 2.2% of the Watchman arm, significantly lower than in PROTECT AF, satisfying the pre-specified safety performance goal. Using a broader, more inclusive definition of adverse effects, these still were lower in PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial than in PROTECT AF (4.2% vs. 8.7%; p = 0.004). Pericardial effusions requiring surgical repair decreased from 1.6% to 0.4% (p = 0.027), and those requiring pericardiocentesis decreased from 2.9% to 1.5% (p = 0.36), although the number of events was small. In this trial, LAA occlusion was noninferior to warfarin for ischemic stroke prevention or SE >7 days' post-procedure. Although noninferiority was not achieved for overall efficacy, event rates were low and numerically comparable in both arms. Procedural safety has significantly improved. This trial provides additional data that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF who do not have an absolute contraindication to short-term warfarin therapy. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Control of Scirtothrips dorsalis with foliar insecticides, 2011

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate the efficacy of several conventional and novel insecticides against a new invasive thrips pest, Scirtothrips dorsalis Hood, in pepper under greenhouse condition. The trial was conducted at Tropical Research and Education Center in Homestead, Florida in hop...

Soil applied insecticidal control of Scirtothrips dorsalis, 2011

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate the efficacy of several conventional and novel soil applied insecticides against a new invasive thrips pest, Scirtothrips dorsalis Hood, in pepper under greenhouse condition. The trial was conducted at Tropical Research and Education Center in Homestead, F...

Control of rugose spiraling whitefly using biological insecticides, 2014

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate the efficacy of selected biological insecticides against a new invasive whitefly pest, Aleurodicus rugioperculatus Martin, in white bird of paradise under field condition. The trial was conducted at United States Horticultural Research Laboratory in Fort P...

A Randomized, Placebo-Controlled Trial of D-Cycloserine for the Enhancementof Social Skills Training in Pervasive Developmental Disorders

DTIC Science & Technology

2015-11-01

report (4) Abstracts: Nothing to report b. List presentations made during the last year (international, national, local societies, military meetings...disorders (ASDs). We evaluated the efficacy, tolerability, and last effects of DCS given one hour prior to each of 10 weekly SST sessions for the...treatment of social impairment in 68 children and young adolescents (ages 5-11 years ) with ASDs during a randomized placebo-controlled trial. The

Learning a novel phonological contrast depends on interactions between individual differences and training paradigm design.

PubMed

Perrachione, Tyler K; Lee, Jiyeon; Ha, Louisa Y Y; Wong, Patrick C M

2011-07-01

Studies evaluating phonological contrast learning typically investigate either the predictiveness of specific pretraining aptitude measures or the efficacy of different instructional paradigms. However, little research considers how these factors interact--whether different students learn better from different types of instruction--and what the psychological basis for any interaction might be. The present study demonstrates that successfully learning a foreign-language phonological contrast for pitch depends on an interaction between individual differences in perceptual abilities and the design of the training paradigm. Training from stimuli with high acoustic-phonetic variability is generally thought to improve learning; however, we found high-variability training enhanced learning only for individuals with strong perceptual abilities. Learners with weaker perceptual abilities were actually impaired by high-variability training relative to a low-variability condition. A second experiment assessing variations on the high-variability training design determined that the property of this learning environment most detrimental to perceptually weak learners is the amount of trial-by-trial variability. Learners' perceptual limitations can thus override the benefits of high-variability training where trial-by-trial variability in other irrelevant acoustic-phonetic features obfuscates access to the target feature. These results demonstrate the importance of considering individual differences in pretraining aptitudes when evaluating the efficacy of any speech training paradigm. © 2011 Acoustical Society of America

Indigenous traditional knowledge and substance abuse treatment outcomes: the problem of efficacy evaluation.

PubMed

Gone, Joseph P

2012-09-01

In the field of substance abuse treatment, American Indian and Alaska Native (AI/AN) communities have routinely incorporated ceremonial practices as one important component in the promotion of recovery and healing. The beneficial effects of such practices are frequently described as plainly apparent by community-based advocates, providers, and professionals alike. In the present era of evidence-based substance abuse intervention, however, indigenous integration of such practices raises questions pertaining to the systematic evaluation of treatment efficacy. The focus of this article is outcome evaluation. Although intervention outcome researchers recognize the randomized controlled trial as the "gold standard" against which claims of treatment efficacy are measured, AI/AN efficacy assertions grounded in indigenous traditional knowledge (ITK) reflect different concerns that have emerged in non-Western historical contexts. The interface between scientific and indigenous "ways of knowing" is explored here relative to efficacy claims about substance abuse treatment. Distinguishing features of both scientific knowing and ITK are summarized and compared. ITK has been described as personal and experiential, reflecting the primacy of autonomous individual knowing. In contrast, intervention scientists are skeptical of personal inference as a basis for efficacy evaluation. The evident divergence between these epistemic paradigms can result in potentially contradictory claims. Proper appraisal of the status and relevance of ITK for determining treatment efficacy requires further exploration of these marginalized approaches to knowledge. Intervention scientists who work in AI/AN communities should remain open to the legitimacy and role of ITKs in investigations of substance abuse treatment.

Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough).

PubMed

Glickman, L T; Appel, M J

1981-08-01

Two field trials were conducted during periods of endemic (summer) and epizootic (winter) canine infectious tracheobronchitis activity to evaluate the efficacy of three intranasal vaccines in a closed commercial beagle breeding kennel. A trivalent vaccine containing Bordetella bronchiseptica, canine parainfluenza, and canine adenovirus-2 was administered at 3 weeks of age. The vaccine was 71.2% and 81.8% effective in decreasing the incidence of coughing during the winter and summer trials, respectively. The number of deaths was lower in each of the vaccine groups than in the placebo groups. No adverse reactions were observed with any of the intranasal vaccines.

Effectiveness versus efficacy trials in COPD: how study design influences outcomes and applicability.

PubMed

Woodcock, Ashley; Boucot, Isabelle; Leather, David A; Crawford, Jodie; Collier, Susan; Bakerly, Nawar Diar; Hilton, Emma; Vestbo, Jørgen

2018-02-01

Guidelines for chronic obstructive pulmonary disease (COPD) management are based largely on results from double-blind randomised controlled trials (RCTs) of efficacy. These trials have high internal validity and test whether a drug is efficacious, but they are conducted in highly selected populations that may differ significantly from patients with COPD seen in routine practice.We compared the baseline characteristics, healthcare use and outcomes between the Salford Lung Study (SLS), an open-label effectiveness RCT, with six recent large-scale efficacy RCTs. We also calculated the proportion of SLS patients who would have been eligible for inclusion in an efficacy RCT by applying the inclusion criteria used in efficacy trials of combination treatments.SLS patients were older, included more females and more current smokers, had more comorbidities (including asthma), and had more often experienced exacerbations prior to inclusion. In the SLS, rates of moderate or severe exacerbations, incidence of overall serious adverse events (SAEs), and SAEs of pneumonia were more frequent. A maximum of 30% of patients enrolled in the SLS would have been eligible for a phase IIIa regulatory exacerbation study.Patients in large COPD efficacy RCTs have limited representativeness compared with an effectiveness trial. This should be considered when interpreting efficacy RCT outcomes and their inclusion into guidelines. Copyright ©ERS 2018.

Rationale and design of a multicentre, prospective, randomised, controlled clinical trial to evaluate the efficacy of the adipose graft transposition procedure in patients with a myocardial scar: the AGTP II trial.

PubMed

Gastelurrutia, Paloma; Gálvez-Montón, Carolina; Cámara, Maria Luisa; Bustamante-Munguira, Juan; García-Pavia, Pablo; Avanzas, Pablo; Alberto San Román, J; Pascual-Figal, Domingo; Teresa, Eduardo de; Crespo-Leiro, Maria G; Manito, Nicolás; Núñez, Julio; Fernández-Avilés, Francisco; Caballero, Ángel; Teis, Albert; Lupón, Josep; Brugada, Ramón; Martín, Carlos; Silva, Jacobo; Revilla-Orodea, Ana; Cánovas, Sergio J; Melero, Jose M; Cuenca-Castillo, Jose J; Gonzalez-Pinto, Angel; Bayes-Genis, Antoni

2017-08-04

Cardiac adipose tissue is a source of progenitor cells with regenerative capacity. Studies in rodents demonstrated that the intramyocardial delivery of cells derived from this tissue improves cardiac function after myocardial infarction (MI). We developed a new reparative approach for damaged myocardium that integrates the regenerative properties of cardiac adipose tissue with tissue engineering. In the adipose graft transposition procedure (AGTP), we dissect a vascularised flap of autologous pericardial adipose tissue and position it over the myocardial scarred area. Following encouraging results in acute and chronic MI porcine models, we performed the clinical trial (NCT01473433, AdiFLAP trial) to evaluate safety in patients with chronic MI undergoing coronary artery bypass graft. The good safety profile and trends in efficacy warranted a larger trial. The AGTP II trial (NCT02798276) is an investigator initiated, prospective, randomised, controlled, multicentre study to assess the efficacy of the AGTP in 108 patients with non-revascularisable MI. Patients will be assigned to standard clinical practice or the AGTP. The primary endpoint is change in necrotic mass ratio by gadolinium enhancement at 91 and 365 days. Secondary endpoints include improvement in regional contractibility by MRI at 91 and 365 days; changes in functional MRI parameters (left ventricular ejection fraction, left and right ventricular geometric remodelling) at 91 and 365 days; levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at 7, 91 and 365 days; appearance of arrhythmias from 24 hour Holter monitoring at 24 hours, and at 91 and 365 days; all cause death or re-hospitalisation at 365 days; and cardiovascular death or re-hospitalisation at 365 days. The institutional review board approved the trial which will comply with the Declaration of Helsinki. All patients will provide informed consent. It may offer a novel, effective and technically simple technique for patients with no other therapeutic options. The results will be submitted to indexed medical journals and national and international meetings. ClinicalTrials.gov: NCT02798276, pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparable efficacy and safety of various topical formulations of terbinafine in tinea pedis irrespective of the treatment regimen: results of a meta-analysis.

PubMed

Korting, Hans Christian; Kiencke, Peter; Nelles, Sandra; Rychlik, Reinhard

2007-01-01

Terbinafine has been widely used with major success as a topical antifungal therapy for tinea pedis (athlete's foot). Its efficacy and safety have been validated in several clinical trials, which have demonstrated clinical efficacy for the drug after only 1 week of treatment when applied once daily, a reflection of the high fungicidal potency of the drug and its ability to form a depot in the upper skin layer. To improve patients' compliance further, a terbinafine-containing film-forming solution has been developed for single-dose therapy of athlete's foot. This novel formulation delivers terbinafine in high amounts and for a prolonged period of time into the skin, making one-shot treatment feasible. Over the past years there have been a variety of trials evaluating use of topical terbinafine addressing different pharmaceutical formulations, treatment durations, and application frequencies, but a detailed meta-analysis of these trials has not been conducted to date. The present study is the first meta-analytic evaluation of the available data on the efficacy (clinical and mycologic cure rates) and safety (adverse events) of all topical forms of terbinafine for the treatment of tinea pedis. An international, systematic literature search of 12 electronic databases (including MEDLINE, EMBASE, and Cochrane databases) using a pre-specified search strategy was conducted in March 2006. This meta-analysis included only randomized controlled trials in which terbinafine had been used for topical treatment of tinea pedis in comparison with placebo or an active control. Studies of all available topical formulations of terbinafine, frequencies of application, and durations of treatment were included. Of 100 identified articles published between 1990 and 2006, 19 met the criteria for analysis. These 19 studies involved 2899 patients with clinical and mycologic diagnoses of tinea pedis (nine placebo-controlled trials and ten active-controlled trials). Efficacy analysis demonstrated that the mycologic cure rate was significantly superior with terbinafine compared with placebo (relative risk [RR] 3.17; p < 0.001). No significant differences in efficacy were found amongst different formulations of terbinafine, treatment durations, or frequencies of application. Comparable results were obtained with respect to clinical cure rate for terbinafine compared with placebo (RR 2.75; p < 0.001). Comparison of the efficacy of terbinafine versus active control indicated a nonsignificant difference in favor of terbinafine with regard to mycologic cure rate (RR 1.03; p = 0.423) and clinical cure rate (RR 1.09; p = 0.11). The median duration of treatment was also shorter with terbinafine (1 week) compared with active controls (2 weeks). Analysis of the placebo-controlled studies showed that there was no significant difference in the risk of adverse events with terbinafine compared with placebo (RR 1.34; p = 0.34). Likewise, no significant differences in adverse events were found between terbinafine and active controls (RR 1.08; p = 0.72). Terbinafine is very well tolerated in any topical pharmaceutical formulation and also has high efficacy as a cure for tinea pedis, irrespective of type of pharmaceutical formulation, treatment duration, and frequency of application, including the recently established one-shot regimen. In addition, terbinafine has an apparently unique advantage over other antifungal agents with respect to the required duration of treatment for tinea pedis.

Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials

PubMed Central

Dong, Hongli; Pi, Fuhua; Ding, Zan; Chen, Wei; Pang, Shaojie; Dong, Wenya; Zhang, Qingying

2015-01-01

Background Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke. Methods A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions. Results B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12. Conclusions B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied. PMID:26355679

Herbal medicine for idiopathic central precocious puberty: A protocol for a systematic review of controlled trials.

PubMed

Lee, Hye Lim; Lee, Yoo Been; Choi, Jun-Yong; Lee, Ju Ah

2018-03-01

Herbal medicine is widely used in East Asia to treat idiopathic central precocious puberty (ICPP). Most of the available clinical trials that investigated herbal medicine for ICPP have been included in this review. This systematic review will assess the efficacy and safety of herbal medicine for ICPP. Eleven databases, including Asian databases, will be searched for studies conducted through 2018. We will include randomized controlled trials assessing herbal medicine for ICPP. The risk of bias will be evaluated using the Cochrane risk of bias assessment tool, and confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation instrument. This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide health care practices. PROSPER 2018 CRD42018087988.

The efficacy and safety of estriol to treat vulvovaginal atrophy in postmenopausal women: a systematic literature review.

PubMed

Rueda, C; Osorio, A M; Avellaneda, A C; Pinzón, C E; Restrepo, O I

2017-08-01

To evaluate the efficacy and safety of estriol for the treatment of vulvovaginal atrophy in postmenopausal women. A systematic literature review was performed. We searched the following electronic databases: Medline, Cochrane, Embase, Lilacs, CINHAL and Google Scholar. The studies selected included controlled clinical trials and quasi-experimental studies. Selections were made in pairs and independently, first by title and abstract and then complete texts. We identified 188 studies, 22 of which met the inclusion criteria; 13 were controlled clinical trials and nine were quasi-experimental, and 1217 women were included. These studies confirmed the efficacy of local estrogens to treat symptoms of vulvovaginal atrophy with few adverse effects reported. Following treatment, serum estriol levels rose, peaking at 1 h. At the 6-month follow-up, there was no increase in serum estriol in treated women. The available evidence (of low and moderate quality) shows that, when administered vaginally, estriol preparations appear to be safe for women who have risk factors related to systemic estrogen therapy.

Designing malaria vaccines to circumvent antigen variability.

PubMed

Ouattara, Amed; Barry, Alyssa E; Dutta, Sheetij; Remarque, Edmond J; Beeson, James G; Plowe, Christopher V

2015-12-22

Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines. Copyright © 2015. Published by Elsevier Ltd.

From bench to almost bedside: the long road to a licensed Ebola virus vaccine.

PubMed

Wong, Gary; Mendoza, Emelissa J; Plummer, Francis A; Gao, George F; Kobinger, Gary P; Qiu, Xiangguo

2018-02-01

The Ebola virus (EBOV) disease epidemic during 2014-16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques. Areas covered: This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans. Expert opinion: Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics.

From bench to almost bedside: The long road to a licensed Ebola virus vaccine

PubMed Central

Wong, Gary; Mendoza, Emelissa J.; Plummer, Francis A.; Gao, George F.; Kobinger, Gary P.; Qiu, Xiangguo

2018-01-01

Introduction The Ebola virus (EBOV) disease epidemic during 2014-16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques. Areas covered This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans. Expert opinion Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics. PMID:29148858

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial.

PubMed

Chabala, Chishala; Turkova, Anna; Thomason, Margaret J; Wobudeya, Eric; Hissar, Syed; Mave, Vidya; van der Zalm, Marieke; Palmer, Megan; Kapasa, Monica; Bhavani, Perumal K; Balaji, Sarath; Raichur, Priyanka A; Demers, Anne-Marie; Hoddinott, Graeme; Owen-Powell, Ellen; Kinikar, Aarti; Musoke, Philippa; Mulenga, Veronica; Aarnoutse, Rob; McIlleron, Helen; Hesseling, Anneke; Crook, Angela M; Cotton, Mark; Gibb, Diana M

2018-04-19

Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. International Standard Randomised Controlled Trials Number: ISRCTN63579542 , 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379 , 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017.

Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke Clinical Trials.

PubMed

Spokoyny, Ilana; Lansberg, Maarten; Thiessen, Rosita; Kemp, Stephanie M; Aksoy, Didem; Lee, YongJae; Mlynash, Michael; Hirsch, Karen G

2016-10-01

Despite several national coordinated research networks, enrollment in many cerebrovascular trials remains challenging. An electronic tool was needed that would improve the efficiency and efficacy of screening for multiple simultaneous acute clinical stroke trials by automating the evaluation of inclusion and exclusion criteria, improving screening procedures and streamlining the communication process between the stroke research coordinators and the stroke clinicians. A multidisciplinary group consisting of physicians, study coordinators, and biostatisticians designed and developed an electronic clinical trial screening tool on a HIPAA (Health Insurance Portability and Accountability Act)-compliant platform. A web-based tool was developed that uses branch logic to determine eligibility for simultaneously enrolling clinical trials and automatically notifies the study coordinator teams about eligible patients. After 12 weeks of use, 225 surveys were completed, and 51 patients were enrolled in acute stroke clinical trials. Compared with the 12 weeks before implementation of the tool, there was an increase in enrollment from 16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and coordinators reported increased satisfaction with the process and improved ease of screening. We created a semiautomated electronic screening tool that uses branch logic to screen patients for stroke clinical trials. The tool has improved efficiency and efficacy of screening, and it could be adapted for use at other sites and in other medical fields. © 2016 American Heart Association, Inc.

Recommendations for the clinical evaluation of agents for treatment of osteoporosis: consensus of an expert panel representing the American Society for Bone and Mineral Research (ASBMR), the International Society for Clinical Densitometry (ISCD), and the National Osteoporosis Foundation (NOF).

PubMed

Silverman, Stuart L; Cummings, Steven R; Watts, Nelson B

2008-01-01

A panel of experts representing ASBMR, NOF, and ISCD reviewed evidence and reached consensus that regulatory approval of treatments for osteoporosis should be based on trials with fracture endpoints, lasting 18-24 mo, and extending treatment to 5 yr; other indications could be approved based on BMD and turnover markers. In response to an FDA request for clinical trial guidance in osteoporosis, an expert panel was convened with representatives from the American Society of Bone and Mineral Research, the International Society of Clinical Densitometry, and the National Osteoporosis Foundation. The panel used a validated evidence-based expert panel process (the Rand Appropriateness Method) to address issues of trial duration, trial design, use of intermediate endpoints as outcomes, and use of placebo-controlled trials in high-risk patients. The panel concluded that placebo-controlled trials with fracture endpoints are appropriate and, with informed consent, are ethical for registration of new compounds. Trials may be 18-24 mo in duration for efficacy, assuming longer duration to 5 yr for safety and demonstration of sustained fracture reduction. Once fracture efficacy has been established for a particular agent, intermediate endpoints (e.g., BMD and bone turnover markers) may be used as outcomes for new indications other than corticosteroid-induced osteoporosis.

Phase-II trials in osteosarcoma recurrences: A systematic review of past experience.

PubMed

Omer, Natacha; Le Deley, Marie-Cécile; Piperno-Neumann, Sophie; Marec-Berard, Perrine; Italiano, Antoine; Corradini, Nadège; Bellera, Carine; Brugières, Laurence; Gaspar, Nathalie

2017-04-01

The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined. To study consistency in phase-II clinical trials evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results. Systematic review of clinical trials registered on clinicaltrials.gov, clinicaltrialsregister.eu and French National Cancer Institute website or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II). Among the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (n = 40), and chemotherapy alone (n = 26). Results were fully (n = 28) or partially (abstract, n = 6) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, n = 40 or best response, n = 31), with various definitions (complete + partial ± minor response and stable disease), mainly evaluated with RECIST criteria (n = 69); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, n = 12) varied from 5% to 25%. No robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fold rise in antibody titers by measured by glycoprotein-based enzyme-linked immunosorbent assay is an excellent correlate of protection for a herpes zoster vaccine, demonstrated via the vaccine efficacy curve.

PubMed

Gilbert, Peter B; Gabriel, Erin E; Miao, Xiaopeng; Li, Xiaoming; Su, Shu-Chih; Parrino, Janie; Chan, Ivan S F

2014-11-15

The phase III Zostavax Efficacy and Safety Trial of 1 dose of licensed zoster vaccine (ZV; Zostavax; Merck) in 50-59-year-olds showed approximately 70% vaccine efficacy (VE) to reduce the incidence of herpes zoster (HZ). An objective of the trial was to assess immune response biomarkers measuring antibodies to varicella zoster virus (VZV) by glycoprotein-based enzyme-linked immunosorbent assay as correlates of protection (CoPs) against HZ. The principal stratification vaccine efficacy curve framework for statistically evaluating immune response biomarkers as CoPs was applied. The VE curve describes how VE against the clinical end point (HZ) varies across participant subgroups defined by biomarker readout measuring vaccine-induced immune response. The VE curve was estimated using several subgroup definitions. The fold rise in VZV antibody titers from the time before immunization to 6 weeks after immunization was an excellent CoP, with VE increasing sharply with fold rise: VE was estimated at 0% for the subgroup with no rise and at 90% for the subgroup with 5.26-fold rise. In contrast, VZV antibody titers measured 6 weeks after immunization did not predict VE, with similar estimated VEs across titer subgroups. The analysis illustrates the value of the VE curve framework for assessing immune response biomarkers as CoPs in vaccine efficacy trials. NCT00534248. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax: A systematic review and meta-analysis.

PubMed

Zuluaga-Idarraga, Lina Marcela; Tamayo Perez, María-Eulalia; Aguirre-Acevedo, Daniel Camilo

2015-12-30

To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax. A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg/kg/ day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated. For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found. Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax.

Efficacy of vedolizumab as induction therapy in refractory IBD patients: Amulticenter cohort

PubMed Central

Shelton, Edward; Allegretti, Jessica R.; Stevens, Betsy; Lucci, Matthew; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Giallourakis, Cosmas; Garber, John; Hamilton, Matthew J; Tomczak, Michal; Makrauer, Fredrick; Burakoff, Robert B; Levine, Jonathan; de Silva, Punyaganie; Friedman, Sonia; Ananthakrishnan, Ashwin; Korzenik, Joshua R.; Yajnik, Vijay

2015-01-01

Background Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission. Results Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%. Conclusions VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials. PMID:26288002

8-Way Randomized Controlled Trial of Doxylamine, Pyridoxine and Dicyclomine for Nausea and Vomiting during Pregnancy: Restoration of Unpublished Information

PubMed Central

Zhang, Rujun; Persaud, Navindra

2017-01-01

Objectives We report information about an unpublished 1970s study (“8-way” Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published. Design Double blinded, multi-centred, randomized placebo-controlled study. Setting 14 clinics in the United States. Participants 2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled. Interventions Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights. Outcomes Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians. Results Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were “evaluated moderate or excellent” was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity. Conclusion The available information about this “8-way Bendectin” trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias. Trial registration Not registered. PMID:28052111

Comparison of the efficacy and safety between interspinous process distraction device and open decompression surgery in treating lumbar spinal stenosis: a meta analysis.

PubMed

Hong, Peiwei; Liu, Yao; Li, Hedong

2015-02-01

The present study performed a meta-analysis to evaluate the efficacy and safety of interspinous process distraction device (IPD) compared with open decompression surgery (ODS) in treating lumbar spinal stenosis. Literatures were searched in the databases including Cochrane Library, Pubmed, OvidSP, Sciencedirect, Web of Science, and Springerlin. Published reviews were checked to track missed original research papers. The quality and bias of publications with randomized controlled trial were evaluated using the tool for assessing risk of bias in the Cochrane handbook. The quality and bias of publications with cohort trial were evaluated using the Newcastle-Ottawa Scale. The grades of literatures were evaluated with the guidelines of Grading of Recommendations Assessment Development and Evaluation (GRADE). Totally, 21 publications matched the inclusion criteria, including 20 different clinical trials and 54,138 patients. The results indicated that there was no significant difference in improvement rate, Oswestry disability index questionnaire (ODI) score, and visual analog scale (VAS) score of back pain or leg pain between IPD group and ODS group. The postoperation complication rate, perioperation blood loss, hospitalization time, and operation time were lower/shorter in IPD group than ODS group. However, the reoperation rate in IPD group was higher than ODS group. The results indicated that IPD has better effects and less complication than ODS. However, because of the higher reoperation rate in IPD than ODS, we failed to conclude that IPD could replace ODS as golden standard but may be a viable alternative in treating lumbar spinal stenosis.

From randomized controlled trials to observational studies.

PubMed

Silverman, Stuart L

2009-02-01

Randomized controlled trials are considered the gold standard in the hierarchy of research designs for evaluating the efficacy and safety of a treatment intervention. However, their results can have limited applicability to patients in clinical settings. Observational studies using large health care databases can complement findings from randomized controlled trials by assessing treatment effectiveness in patients encountered in day-to-day clinical practice. Results from these designs can expand upon outcomes of randomized controlled trials because of the use of larger and more diverse patient populations with common comorbidities and longer follow-up periods. Furthermore, well-designed observational studies can identify clinically important differences among therapeutic options and provide data on long-term drug effectiveness and safety.

A Randomized Trial of a Hepatitis Care Coordination Model in Methadone Maintenance Treatment

PubMed Central

Delucchi, Kevin L.; McKnight, Courtney; Hettema, Jennifer; Khalili, Mandana; Min, Albert; Jordan, Ashly E.; Pepper, Nicole; Hall, Jessica; Hengl, Nicholas S.; Young, Christopher; Shopshire, Michael S.; Manuel, Jennifer K.; Coffin, Lara; Hammer, Hali; Shapiro, Bradley; Seewald, Randy M.; Bodenheimer, Henry C.; Sorensen, James L.; Des Jarlais, Don C.; Perlman, David C.

2013-01-01

Objectives. We evaluated the efficacy of a hepatitis care coordination intervention to improve linkage to hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination and clinical evaluation of hepatitis C virus (HCV) infection among methadone maintenance patients. Methods. We conducted a randomized controlled trial of 489 participants from methadone maintenance treatment programs in San Francisco, California, and New York City from February 2008 through June 2011. We randomized participants to a control arm (n = 245) and an intervention arm (n = 244), which included on-site screening, motivational-enhanced education and counseling, on-site vaccination, and case management services. Results. Compared with the control group, intervention group participants were significantly more likely (odds ratio [OR] = 41.8; 95% confidence interval [CI] = 19.4, 90.0) to receive their first vaccine dose within 30 days and to receive an HCV evaluation within 6 months (OR = 4.10; 95% CI = 2.35, 7.17). A combined intervention adherence outcome that measured adherence to HAV–HBV vaccination, HCV evaluation, or both strongly favored the intervention group (OR = 8.70; 95% CI = 5.56, 13.61). Conclusions. Hepatitis care coordination was efficacious in increasing adherence to HAV–HBV vaccination and HCV clinical evaluation among methadone patients. PMID:23947319

Impact of polymer formulations on neointimal proliferation after zotarolimus-eluting stent with different polymers: insights from the RESOLUTE trial.

PubMed

Waseda, Katsuhisa; Ako, Junya; Yamasaki, Masao; Koizumi, Tomomi; Sakurai, Ryota; Hongo, Yoichiro; Koo, Bon-Kwon; Ormiston, John; Worthley, Stephen G; Whitbourn, Robert J; Walters, Darren L; Meredith, Ian T; Fitzgerald, Peter J; Honda, Yasuhiro

2011-06-01

Polymer formulation may affect the efficacy of drug-eluting stents. Resolute, Endeavor, and ZoMaxx are zotarolimus-eluting stents with different stent platforms and different polymer coatings and have been tested in clinical trials. The aim of this analysis was to compare the efficacy of zotarolimus-eluting stents with different polymers. Data were obtained from the first-in man trial or first randomized trials of each stent, The Clinical RESpOnse EvaLUation of the MedTronic Endeavor CR ABT-578 Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (RESOLUTE), Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II), and ZoMaxx I trials. Follow-up intravascular ultrasound analyses (8 to 9 months of follow-up) were possible in 353 patients (Resolute: 88, Endeavor: 98, ZoMaxx: 82, Driver: 85). Volume index (volume/stent length) was obtained for vessel, stent, lumen, peristent plaque, and neointima. Cross-sectional narrowing was defined as neointimal area divided by stent area (%). Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. At baseline, vessel, lumen, and peristent plaque volume index were not significantly different among the 4 stent groups. At follow-up, percent neointimal obstruction was significantly lower in Resolute compared with Endeavor, ZoMaxx, and Driver (Resolute: 3.7±4.0, Endeavor: 17.5±10.1, ZoMaxx: 14.6±8.1, Driver: 29.4±17.2%; P<0.001). Greater maximum cross-sectional narrowing and higher neointima-free frame ratio, suggesting less neointimal coverage, were observed in Resolute compared with other stent groups. Multiple regression analysis confirmed that the biodurable polymer used in Resolute independently correlated with neointimal suppression among 3 zotarolimus-eluting stents. The different polymer formulations significantly affect the relative amount of neointima for zotarolimus-eluting stents. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00248079.

Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials

PubMed Central

2013-01-01

Background Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD) is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia. Methods A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs) involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Results Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information. Conclusions Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed. PMID:23336848

Management of functional dyspepsia: Unsolved problems and new perspectives.

PubMed

Madisch, Ahmed; Miehlke, Stephan; Labenz, Joachim

2005-11-14

The common characteristic criteria of all functional gastrointestinal (GI) disorders are the persistence and recurrence of variable gastrointestinal symptoms that cannot be explained by any structural or biochemical abnormalities. Functional dyspepsia (FD) represents one of the important GI disorders in Western countries because of its remarkably high prevalence in general population and its impact on quality of life. Due to its dependence on both subjective determinants and diverse country-specific circumstances, the definition and management strategies of FD are still variably stated. Clinical trials with several drug classes (e.g., proton pump inhibitors, H2-blockers, prokinetic drugs) have been performed frequently without validated disease-specific test instruments for the outcome measurements. Therefore, the interpretation of such trials remains difficult and controversial with respect to comparability and evaluation of drug efficacy, and definite conclusions can be drawn neither for diagnostic management nor for efficacious drug therapy so far. In view of these unsolved problems, guidelines both on the clinical management of FD and on the performance of clinical trials are needed. In recent years, increasing research work has been done in this area. Clinical trials conducted in adequately diagnosed patients that provided validated outcome measurements may result in better insights leading to more effective treatment strategies. Encouraging perspectives have been recently performed by methodologically well-designed treatment studies with herbal drug preparations. Herbal drugs, given their proven efficacy in clinical trials, offer a safe therapeutic alternative in the treatment of FD which is often favored by both patients and physicians. A fixed combination of peppermint oil and caraway oil in patients suffering from FD could be proven effective by well-designed clinical trials.

Overnight switch from ropinirole to transdermal rotigotine patch in patients with Parkinson disease

PubMed Central

2011-01-01

Background A recent trial involving predominantly Caucasian subjects with Parkinson Disease (PD) showed switching overnight from an oral dopaminergic agonist to the rotigotine patch was well tolerated without loss of efficacy. However, no such data have been generated for Korean patients. Methods This open-label multicenter trial investigated PD patients whose symptoms were not satisfactorily controlled by ropinirole, at a total daily dose of 3 mg to 12 mg, taken as monotherapy or as an adjunct to levodopa. Switching treatment from oral ropinirole to transdermal rotigotine was carried out overnight, with a dosage ratio of 1.5:1. After a 28-day treatment period, the safety and tolerability of switching was evaluated. Due to the exploratory nature of this trial, the effects of rotigotine on motor and nonmotor symptoms of PD were analyzed in a descriptive manner. Results Of the 116 subjects who received at least one treatment, 99 (85%) completed the 28-day trial period. Dose adjustments were required for 11 subjects who completed the treatment period. A total of 76 treatment-emergent adverse events (AEs) occurred in 45 subjects. No subject experienced a serious AE. Thirteen subjects discontinued rotigotine prematurely due to AEs. Efficacy results suggested improvements in both motor and nonmotor symptoms and quality of life after switching. Fifty-two subjects (46%) agreed that they preferred using the patch over oral medications, while 31 (28%) disagreed. Conclusions Switching treatment overnight from oral ropinirole to transdermal rotigotine patch, using a dosage ratio of 1.5:1, was well tolerated in Korean patients with no loss of efficacy. Trial registration This trial is registered with the ClincalTrails.gov Registry (NCT00593606). PMID:21831297

Eligibility for clinical trials in primary Sjögren’s syndrome: lessons from the UK Primary Sjögren’s Syndrome Registry

PubMed Central

Oni, Clare; Mitchell, Sheryl; James, Katherine; Ng, Wan-Fai; Griffiths, Bridget; Hindmarsh, Victoria; Price, Elizabeth; Pease, Colin T.; Emery, Paul; Lanyon, Peter; Jones, Adrian; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Hunter, John; Gupta, Monica; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Barone, Francesca; Fisher, Ben; Rauz, Saaeha; Richards, Andrea; Bowman, Simon J.

2016-01-01

Abstract Objective: To identify numbers of participants in the UK Primary Sjögren’s Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. Methods: We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. Results: In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren’s Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren’s syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren’s Syndrome study (Tocilizumab), 46.3% for the Tolerance and Efficacy of Rituximab in Sjögren’s Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren’s Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. Conclusion: The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters. PMID:26510429

Making Sense of a Negative Clinical Trial Result: A Bayesian Analysis of a Clinical Trial of Lorazepam and Diazepam for Pediatric Status Epilepticus.

PubMed

Chamberlain, Daniel B; Chamberlain, James M

2017-01-01

We demonstrate the application of a Bayesian approach to a recent negative clinical trial result. A Bayesian analysis of such a trial can provide a more useful interpretation of results and can incorporate previous evidence. This was a secondary analysis of the efficacy and safety results of the Pediatric Seizure Study, a randomized clinical trial of lorazepam versus diazepam for pediatric status epilepticus. We included the published results from the only prospective pediatric study of status in a Bayesian hierarchic model, and we performed sensitivity analyses on the amount of pooling between studies. We evaluated 3 summary analyses for the results: superiority, noninferiority (margin <-10%), and practical equivalence (within ±10%). Consistent with the original study's classic analysis of study results, we did not demonstrate superiority of lorazepam over diazepam. There is a 95% probability that the true efficacy of lorazepam is in the range of 66% to 80%. For both the efficacy and safety outcomes, there was greater than 95% probability that lorazepam is noninferior to diazepam, and there was greater than 90% probability that the 2 medications are practically equivalent. The results were largely driven by the current study because of the sample sizes of our study (n=273) and the previous pediatric study (n=61). Because Bayesian analysis estimates the probability of one or more hypotheses, such an approach can provide more useful information about the meaning of the results of a negative trial outcome. In the case of pediatric status epilepticus, it is highly likely that lorazepam is noninferior and practically equivalent to diazepam. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: Protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial.

PubMed

Fan, Dazhi; Wu, Shuzhen; Ye, Shaoxin; Wang, Wen; Guo, Xiaoling; Liu, Zhengping

2017-11-01

Uterine niche is defined as a triangular anechoic structure at the site of the scar or a gap in the myometrium at the site of a previous caesarean section. The main clinical manifestations are postmenstrual spotting and intrauterine infection, which may seriously affect the daily life of nonpregnant women. Trials have shown an excellent safety and efficacy for the potential of mesenchymal stem cells (MSCs) as a therapeutic option for scar reconstruction. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment for the uterine niche. This phase II clinical trial is a single-center, prospective, randomized, double-blind, placebo-controlled with 2 arms. One hundred twenty primiparous participants will be randomly (1:1 ratio) assigned to receive direct intramuscular injection of MSCs (a dose of 1*10 cells in 1 mL of 0.9% saline) (MSCs group) or an identical-appearing 1 mL of 0.9% saline (placebo-controlled group) near the uterine incision. The primary outcome of this trial is to evaluate the proportion of participants at 6 months who is found uterine niche in the uterus by transvaginal utrasonography. Adverse events will be documented in a case report form. The study will be conducted at the Department of Obstetric of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan. This trial is the first investigation of the potential for therapeutic use of MSCs for the management of uterine niche after cesarean delivery. This protocol will help to determine the efficacy and safety of MSCs treatment in uterine niche and bridge the gap with regards to the current preclinical and clinical evidence. NCT02968459 (Clinical Trials.gov: http://clinicaltrials.gov/).

Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche

PubMed Central

Fan, Dazhi; Wu, Shuzhen; Ye, Shaoxin; Wang, Wen; Guo, Xiaoling; Liu, Zhengping

2017-01-01

Abstract Background: Uterine niche is defined as a triangular anechoic structure at the site of the scar or a gap in the myometrium at the site of a previous caesarean section. The main clinical manifestations are postmenstrual spotting and intrauterine infection, which may seriously affect the daily life of nonpregnant women. Trials have shown an excellent safety and efficacy for the potential of mesenchymal stem cells (MSCs) as a therapeutic option for scar reconstruction. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment for the uterine niche. Methods/design: This phase II clinical trial is a single-center, prospective, randomized, double-blind, placebo-controlled with 2 arms. One hundred twenty primiparous participants will be randomly (1:1 ratio) assigned to receive direct intramuscular injection of MSCs (a dose of 1∗107 cells in 1 mL of 0.9% saline) (MSCs group) or an identical-appearing 1 mL of 0.9% saline (placebo-controlled group) near the uterine incision. The primary outcome of this trial is to evaluate the proportion of participants at 6 months who is found uterine niche in the uterus by transvaginal utrasonography. Adverse events will be documented in a case report form. The study will be conducted at the Department of Obstetric of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan. Discussion: This trial is the first investigation of the potential for therapeutic use of MSCs for the management of uterine niche after cesarean delivery. Conclusion: This protocol will help to determine the efficacy and safety of MSCs treatment in uterine niche and bridge the gap with regards to the current preclinical and clinical evidence. Trial registration number: NCT02968459 (Clinical Trials.gov: http://clinicaltrials.gov/). PMID:29095305

A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome

PubMed Central

2009-01-01

Background Irritable Bowel Syndrome (IBS) is a common chronic gastrointestinal disorder and the evidence for efficacy of most drug therapies in the treatment of IBS is weak. A popular alternative is probiotics, which have been used in several conditions. including IBS. Probiotics are live microbial food supplements. The aim of this systematic review and meta-analysis of randomized trials study was to evaluate the efficacy of probiotics in alleviating symptoms in patients with irritable bowel syndrome. We searched Ovid versions of MEDLINE (1950–2007), EMBASE (1980–2007), CINAHL (1982–2007), AMED (1985–2007), the Cochrane library and hand searched retrieved papers. Results We identified 14 randomized placebo controlled trials. Combined data suggested a modest improvement in overall symptoms after several weeks of treatment: for dichotomous data from seven trials the overall Odds Ratio (OR) was 1.6 (95% CI, 1.2 to 2.2); for continuous data from six trials the standardised mean difference (SMD) was 0.23 (95% CI, 0.07 to 0.38). For individual symptoms the results differed between the pooled dichotomous and pooled continuous data. Trials varied in relation to the length of treatment (4–26 weeks), dose, organisms and strengths of probiotics used. Conclusion Probiotics may have a role in alleviating some of the symptoms of IBS, a condition for which currently evidence of efficacy of drug therapies is weak. However, as IBS is a condition that is chronic and usually intermittent longer term trials are recommended. Such research should focus on the type, optimal dose of probiotics and the subgroups of patients who are likely to benefit the most. PMID:19220890

Eligibility for clinical trials in primary Sjögren's syndrome: lessons from the UK Primary Sjögren's Syndrome Registry.

PubMed

Oni, Clare; Mitchell, Sheryl; James, Katherine; Ng, Wan-Fai; Griffiths, Bridget; Hindmarsh, Victoria; Price, Elizabeth; Pease, Colin T; Emery, Paul; Lanyon, Peter; Jones, Adrian; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Hunter, John; Gupta, Monica; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Barone, Francesca; Fisher, Ben; Rauz, Saaeha; Richards, Andrea; Bowman, Simon J

2016-03-01

To identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Curative control of Scirtothrips dorsalis with biological insecticides, 2011

USDA-ARS?s Scientific Manuscript database

The objective of this study was 1) to evaluate the efficacy of the selected entomopathogens against a new invasive thrips pest, chilli thrips Scirtothrips dorsalis, in pepper, and 2) compare potential of entomopathogens with a chemical standard under greenhouse condition. The trial was conducted at ...

Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial.

PubMed Central

Ferrari, M. L. A.; Coelho, P. M. Z.; Antunes, C. M. F.; Tavares, C. A. P.; da Cunha, A. S.

2003-01-01

OBJECTIVE: To evaluate the therapeutic efficacy of oxamniquine and praziquantel, the two most clinically important schistosomicide drugs, and to compare the accuracy of faecal examination with the accuracy of oogram in testing for Schistosoma mansoni infection. METHODS: In a triple-masked and randomized controlled trial, 106 patients infected with S. mansoni were randomly allocated to one of three statistically homogeneous groups. One group was given 60 mg/kg praziquantel per day for three consecutive days, another was given two daily doses of 10 mg/kg oxamniquine, and the placebo group received starch. Faecal examinations (days 15, 30, 60, 90, 120, 150, and 180 after treatment) and biopsy of rectal mucosa by quantitative oogram (days 30, 60, 120, and 180) were used for the initial diagnosis and for evaluating the degree of cure. The chi2 test and the Kruskal-Wallis test were used to compare variables in the three groups. Survival analysis (Kaplan-Meier) and the log-rank test were used to evaluate the efficacy of the treatments. FINDINGS: The sensitivity of stool examinations ranged from 88.9% to 94.4% when patients presented with >5000 S. mansoni eggs per gram of tissue (oogram); when the number of eggs dropped to <1000 eggs per gram, sensitivity was reduced (range, 22.7-34.0%). When cure was evaluated by stool examination, oxamniquine and praziquantel had cure rates of 90.3% and 100%, respectively. However, when the oogram was used as an indicator of sensitivity, the oxamniquine cure rate dropped dramatically (to 42.4%), whereas the rate for praziquantel remained high, at 96.1%. CONCLUSIONS: Praziquantel was significantly more effective than oxamniquine in treating S. mansoni infection. The oogram was markedly more sensitive than stool examinations in detecting S. mansoni eggs and should be recommended for use in clinical trials with schistosomicides. PMID:12764515

Fluvastatin in the prevention of renal transplant vasculopathy: results of a prospective, randomized, double-blind, placebo-controlled trial.

PubMed

Serón, Daniel; Oppenheimer, Federico; Pallardó, Luis M; Lauzurica, Ricardo; Errasti, Pedro; Gomez-Huertas, Ernesto; Bosmans, Jean Louis; Sanchez-Plumed, Jaime; Romero, Rafael; Marques, María; Fulladosa, Xavier; Moreso, Francesc

2008-07-15

Statins prevent the progression of transplant vasculopathy in heart transplants, but its beneficial effect on the transplanted kidney is controversial. The aim is to evaluate the utility of fluvastatin 80 mg/day to reduce the progression of 6-month renal transplant vasculopathy in a multicenter, prospective, randomized, placebo-controlled trial stratified according to donor age. All patients received cyclosporine, mycophenolate mofetil, and prednisone. The progression of transplant vasculopathy was evaluated in paired donor and 6-month protocol biopsies. The primary efficacy variable was the progression of mean arterial intimal volume fraction (deltaVvintima/artery) evaluated with histomorphometry. The minimum sample size to detect a 50% reduction in the progression of deltaVvintima/artery was 62 patients per group. The secondary efficacy variable included the incidence of transplant vasculopathy evaluated according to Banff criteria. A total of 89 patients were included, 74 completed the 6-month study and 57 have paired biopsies with sufficient tissue for histological evaluation. The deltaVvintima/artery was not different between treatment and placebo groups (6.9+/-8.2% vs. 6.9+/-7.4%, P=ns), whereas the incidence of transplant vasculopathy was lower in the fluvastatin group (7% vs. 33%; P=0.02). Because there was a discrepancy between the primary and secondary efficacy variables, post hoc analysis was performed to evaluate the reproducibility of both variables in a subset of 50 biopsies. The reproducibility of transplant vasculopathy was higher than the reproducibility of Vvintima/artery (kappa 0.86 vs. 0.33). In summary, there were no differences in deltaVvintima/artery between groups, but fluvastatin treatment was associated with a reduced incidence of transplant vasculopathy.

Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacy

PubMed Central

Chesi, Marta; Matthews, Geoffrey M.; Garbitt, Victoria M.; Palmer, Stephen E.; Shortt, Jake; Lefebure, Marcus; Stewart, A. Keith; Johnstone, Ricky W.

2012-01-01

The attrition rate for anticancer drugs entering clinical trials is unacceptably high. For multiple myeloma (MM), we postulate that this is because of preclinical models that overemphasize the antiproliferative activity of drugs, and clinical trials performed in refractory end-stage patients. We validate the Vk*MYC transgenic mouse as a faithful model to predict single-agent drug activity in MM with a positive predictive value of 67% (4 of 6) for clinical activity, and a negative predictive value of 86% (6 of 7) for clinical inactivity. We identify 4 novel agents that should be prioritized for evaluation in clinical trials. Transplantation of Vk*MYC tumor cells into congenic mice selected for a more aggressive disease that models end-stage drug-resistant MM and responds only to combinations of drugs with single-agent activity in untreated Vk*MYC MM. We predict that combinations of standard agents, histone deacetylase inhibitors, bromodomain inhibitors, and hypoxia-activated prodrugs will demonstrate efficacy in the treatment of relapsed MM. PMID:22451422

Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials

PubMed Central

Koh, Kim Hwee

2016-01-01

Adhesive capsulitis is a common cause of shoulder pain and limited movement. The objectives of this review were to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis and to evaluate the optimum dose and anatomical site of injections. PubMed and CENTRAL databases were searched for randomised trials and a total of ten trials were included. Results revealed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks). There was no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks. Dosages of intra-articular triamcinolone 20 mg and 40 mg showed identical outcomes, while subacromial and glenohumeral corticosteroid injections had similar efficacy. The use of corticosteroid injections is also generally safe, with infrequent and minor side effects. Physicians may consider corticosteroid injection to treat adhesive capsulitis, especially in the early stages when pain is the predominant presentation. PMID:27570870

Corticosteroid injection for adhesive capsulitis in primary care: a systematic review of randomised clinical trials.

PubMed

Koh, Kim Hwee

2016-12-01

Adhesive capsulitis is a common cause of shoulder pain and limited movement. The objectives of this review were to assess the efficacy and safety of corticosteroid injections for adhesive capsulitis and to evaluate the optimum dose and anatomical site of injections. PubMed and CENTRAL databases were searched for randomised trials and a total of ten trials were included. Results revealed that corticosteroid injection is superior to placebo and physiotherapy in the short-term (up to 12 weeks). There was no difference in outcomes between corticosteroid injection and oral nonsteroidal anti-inflammatory drugs at 24 weeks. Dosages of intra-articular triamcinolone 20 mg and 40 mg showed identical outcomes, while subacromial and glenohumeral corticosteroid injections had similar efficacy. The use of corticosteroid injections is also generally safe, with infrequent and minor side effects. Physicians may consider corticosteroid injection to treat adhesive capsulitis, especially in the early stages when pain is the predominant presentation. Copyright: © Singapore Medical Association.

Targeting Protein Homeostasis in Sporadic Inclusion Body Myositis

PubMed Central

Ahmed, Mhoriam; Machado, Pedro M.; Miller, Adrian; Spicer, Charlotte; Herbelin, Laura; He, Jianghua; Noel, Janelle; Wang, Yunxia; McVey, April L.; Pasnoor, Mamatha; Gallagher, Philip; Statland, Jeffrey; Lu, Ching-Hua; Kalmar, Bernadett; Brady, Stefen; Sethi, Huma; Samandouras, George; Parton, Matt; Holton, Janice L.; Weston, Anne; Collinson, Lucy; Taylor, J. Paul; Schiavo, Giampietro; Hanna, Michael G.; Barohn, Richard J.; Dimachkie, Mazen M.; Greensmith, Linda

2016-01-01

Sporadic inclusion body myositis (sIBM) is the commonest severe myopathy in patients over age 50. Previous therapeutic trials have targeted the inflammatory features of sIBM, but all have failed. Since protein dyshomeostasis may also play a role in sIBM, we tested the effects of targeting this feature of the disease. Using rat myoblast cultures, we found that up-regulation of the heat shock response with Arimoclomol reduced key pathological markers of sIBM in vitro. Furthermore, in mutant valosin-containing protein VCP mice, which develop an inclusion body myopathy (IBM), treatment with Arimoclomol ameliorated disease pathology and improved muscle function. We therefore evaluated the safety and tolerability of Arimoclomol in an investigator-lead, randomised, double-blind, placebo-controlled, proof-of-concept patient trial and gathered exploratory efficacy data which showed that Arimoclomol was safe and well tolerated. Although Arimoclomol improved some IBM-like pathology in vitro and in vivo in the mutant VCP mouse, we did not see statistically significant evidence of efficacy in this proof of concept patient trial. PMID:27009270

Zika vaccines and therapeutics: landscape analysis and challenges ahead.

PubMed

Wilder-Smith, Annelies; Vannice, Kirsten; Durbin, Anna; Hombach, Joachim; Thomas, Stephen J; Thevarjan, Irani; Simmons, Cameron P

2018-06-06

Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines. Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations. In addition to a vaccine, drugs for primary prophylaxis, post-exposure prophylaxis, or treatment should also be developed to prevent or mitigate the severity of congenital Zika syndrome. Establishing the feasibility of immune correlates and/or surrogates are a priority. Given the challenges in conducting phase 3 trials at a time of waning incidence, human challenge trials should be considered to evaluate efficacy. Continued financial support and engagement of industry partners will be essential to the successful development, licensure, and accessibility of Zika vaccines or therapeutics.

Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.

PubMed

Angel, Juana; Steele, A Duncan; Franco, Manuel A

2014-01-01

Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study.

PubMed

Rogawski, Elizabeth T; Platts-Mills, James A; Colgate, E Ross; Haque, Rashidul; Zaman, K; Petri, William A; Kirkpatrick, Beth D

2018-03-05

The low efficacy of rotavirus vaccines in clinical trials performed in low-resource settings may be partially explained by acquired immunity from natural exposure, especially in settings with high disease incidence. In a clinical trial of monovalent rotavirus vaccine in Bangladesh, we compared the original per-protocol efficacy estimate to efficacy derived from a recurrent events survival model in which children were considered naturally exposed and potentially immune after their first rotavirus diarrhea (RVD) episode. We then simulated trial cohorts to estimate the expected impact of prior exposure on efficacy estimates for varying rotavirus incidence rates and vaccine efficacies. Accounting for natural immunity increased the per-protocol vaccine efficacy estimate against severe RVD from 63.1% (95% confidence interval [CI], 33.0%-79.7%) to 70.2% (95% CI, 44.5%-84.0%) in the postvaccination period, and original year 2 efficacy was underestimated by 14%. The simulations demonstrated that this expected impact increases linearly with RVD incidence, will be greatest for vaccine efficacies near 50%, and can reach 20% in settings with high incidence and low efficacy. High rotavirus incidence leads to predictably lower vaccine efficacy estimates due to the acquisition of natural immunity in unvaccinated children, and this phenomenon should be considered when comparing efficacy estimates across settings. NCT01375647.

Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines

PubMed Central

2013-01-01

Background Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. Discussion The Malaria Vaccine Technology Roadmap’s goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%’. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. Conclusions Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine. PMID:24228861

What Makes a Difference: Early Head Start Evaluation Findings in a Developmental Context

ERIC Educational Resources Information Center

Love, John M.; Chazan-Cohen, Rachel; Raikes, Helen; Brooks-Gunn, Jeanne

2013-01-01

The federal Early Head Start (EHS) program began in 1995, and a randomized trial was conducted to evaluate the efficacy of 17 EHS programs. In all, 3,001 low-income families (35% African American, 24% Hispanic, and 37% White) with a pregnant women or an infant under the age of 12 months were randomly assigned to a treatment or control group (with…

Improving mental health of adolescents with Type 1 diabetes: protocol for a randomized controlled trial of the Nothing Ventured Nothing Gained online adolescent and parenting support intervention

PubMed Central

2013-01-01

Background Management of Type 1 diabetes comes with substantial personal and psychological demands particularly during adolescence, placing young people at significant risk for mental health problems. Supportive parenting can mitigate these risks, however the challenges associated with parenting a child with a chronic illness can interfere with a parent’s capacity to parent effectively. Interventions that provide support for both the adolescent and their parents are needed to prevent mental health problems in adolescents; to support positive parent-adolescent relationships; and to empower young people to better self-manage their illness. This paper presents the research protocol for a study evaluating the efficacy of the Nothing Ventured Nothing Gained online adolescent and parenting intervention which aims to improve the mental health outcomes of adolescents with Type 1 diabetes. Method/Design A randomized controlled trial using repeated measures with two arms (intervention and wait-list control) will be used to evaluate the efficacy and acceptability of the online intervention. Approximately 120 adolescents with Type 1 diabetes, aged 13–18 years and one of their parents/guardians will be recruited from pediatric diabetes clinics across Victoria, Australia. Participants will be randomized to receive the intervention immediately or to wait 6 months before accessing the intervention. Adolescent, parent and family outcomes will be assessed via self-report questionnaires at three time points (baseline, 6 weeks and 6 months). The primary outcome is improved adolescent mental health (depression and anxiety). Secondary outcomes include adolescent behavioral (diabetes self-management and risk taking behavior), psychosocial (diabetes relevant quality of life, parent reported child well-being, self-efficacy, resilience, and perceived illness benefits and burdens); metabolic (HbA1c) outcomes; parent psychosocial outcomes (negative affect and fatigue, self-efficacy, and parent experience of child illness); and family outcomes (parent and adolescent reported parent-adolescent communication, responsibility for diabetes care, diabetes related conflict). Process variables including recruitment, retention, intervention completion and intervention satisfaction will also be assessed. Discussion The results of this study will provide valuable information about the efficacy, acceptability and therefore the viability of delivering online interventions to families affected by chronic illnesses such as Type 1 diabetes. Trial registration Australian New Zealand clinical trials registry (ANZCTR); ACTRN12610000170022 PMID:24341465

Clinical efficacy and safety of bevacizumab monotherapy in patients with metastatic melanoma: predictive importance of induced early hypertension.

PubMed

Schuster, Cornelia; Eikesdal, Hans P; Puntervoll, Hanne; Geisler, Jürgen; Geisler, Stephanie; Heinrich, Daniel; Molven, Anders; Lønning, Per E; Akslen, Lars A; Straume, Oddbjørn

2012-01-01

VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12-49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab. ClinicalTrials.gov NCT00139360.

Efficacy of isoniazid prophylactic therapy in prevention of tuberculosis in children: a meta–analysis

PubMed Central

2014-01-01

Background Children are highly susceptible to tuberculosis; thus, there is need for safe and effective preventive interventions. Our objective was to evaluate the efficacy of isoniazid in prevention of tuberculosis morbidity and mortality in children aged 15 years or younger by performing a meta-analysis of randomized controlled trials. To our knowledge, this is the first meta-analysis evaluating efficacy of isoniazid prophylaxis in prevention of tuberculosis in children. Methods A systematic search of the literature was done to identify randomized controlled trials evaluating isoniazid prophylaxis efficacy among children. Each study was evaluated for relevance and validity for inclusion in the analysis. Subgroup analyses were conducted based on study quality, HIV status, tuberculosis endemicity, type of prophylaxis and age of participants. Results Eight studies comprising 10,320 participants were included in this analysis. Upon combining data from all eight studies, isoniazid prophylaxis was found to be efficacious in preventing development of tuberculosis, with a pooled RR of 0.65 (95% CI 0.47, 0.89) p = 0.004 , with confidence intervals adjusted for heterogeneity. Among the sub-group analyses conducted, only age of the participants yielded dramatic differences in the summary estimate of efficacy, suggesting that age might be an effect modifier of the efficacy of isoniazid among children, with no effect realised in children initiating isoniazid at four months of age or earlier and an effect being present in older children. Excluding studies in which isoniazid was initiated at four months of age or earlier yielded an even stronger effect (RR = 0.41 (95% CI 0.31, 0.55) p <0.001). Data on the effect of isoniazid on all-cause mortality, excluding studies in which isoniazid was initiated in infants, yielded an imprecise estimate of mortality benefit (RR = 0.58 (95% CI 0.31, 1.09) p = 0.092). Conclusion Isoniazid prophylaxis reduces the risk of developing tuberculosis by 59% among children aged 15 years or younger excluding children initiated during early infancy for primary prophylaxis (RR = 0.41, 95% CI 0.31, 0.55 p < 0.001) . However, further studies are needed to assess effects on mortality and to determine prophylaxis effectiveness in very young children and among HIV-infected children. PMID:24555539

Study protocol of Prednisone in episodic Cluster Headache (PredCH): a randomized, double-blind, placebo-controlled parallel group trial to evaluate the efficacy and safety of oral prednisone as an add-on therapy in the prophylactic treatment of episodic cluster headache with verapamil

PubMed Central

2013-01-01

Background Episodic cluster headache (ECH) is a primary headache disorder that severely impairs patient’s quality of life. First-line therapy in the initiation of a prophylactic treatment is verapamil. Due to its delayed onset of efficacy and the necessary slow titration of dosage for tolerability reasons prednisone is frequently added by clinicians to the initial prophylactic treatment of a cluster episode. This treatment strategy is thought to effectively reduce the number and intensity of cluster attacks in the beginning of a cluster episode (before verapamil is effective). This study will assess the efficacy and safety of oral prednisone as an add-on therapy to verapamil and compare it to a monotherapy with verapamil in the initial prophylactic treatment of a cluster episode. Methods and design PredCH is a prospective, randomized, double-blind, placebo-controlled trial with parallel study arms. Eligible patients with episodic cluster headache will be randomized to a treatment intervention with prednisone or a placebo arm. The multi-center trial will be conducted in eight German headache clinics that specialize in the treatment of ECH. Discussion PredCH is designed to assess whether oral prednisone added to first-line agent verapamil helps reduce the number and intensity of cluster attacks in the beginning of a cluster episode as compared to monotherapy with verapamil. Trial registration German Clinical Trials Register DRKS00004716 PMID:23889923

Pharmacological interventions for daytime sleepiness and sleep disorders in Parkinson's disease: Systematic review and meta-analysis.

PubMed

Rodrigues, Tiago Martins; Castro Caldas, Ana; Ferreira, Joaquim J

2016-06-01

Daytime sleepiness and sleep disorders are frequently reported in Parkinson's disease (PD). However, their impact on quality of life has been underestimated and few clinical trials have been performed. We aimed to assess the efficacy and safety of pharmacological interventions for daytime sleepiness and sleep disorders in PD. Systematic review of randomized controlled trials comparing any pharmacological intervention with no intervention or placebo for the treatment of daytime sleepiness and sleep problems in PD patients. Ten studies (n = 338 patients) were included. Four trials addressed interventions for excessive daytime sleepiness. Meta-analysis of the three trials evaluating modafinil showed a significant reduction in sleepiness, as assessed by the Epworth Sleepiness Scale (ESS) (- 2.24 points, 95% CI - 3.90 to - 0.57, p < 0.05). In one study, treatment with caffeine was associated with a non-significant improvement of 1.71 points in ESS (95% CI, - 3.57 to 0.13). The six remaining trials assessed interventions for insomnia and REM sleep Behaviour Disorder (RBD). Single study results suggest that doxepin and YXQN granules might be efficacious, while pergolide may be deleterious for insomnia and that rivastigmine may be used to treat RBD in PD patients. However, there is insufficient evidence to support or refute the efficacy of any of these interventions. No relevant side effects were reported. Whilst providing recommendations, this systematic review depicts the lack of a body of evidence regarding the treatment of sleep disorders in PD patients; hence, further studies are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy of Intensive Control of Glucose in Stroke Prevention: A Meta-Analysis of Data from 59197 Participants in 9 Randomized Controlled Trials

PubMed Central

Zhang, Chi; Zhou, Yu-Hao; Xu, Chun-Li; Chi, Feng-Ling; Ju, Hai-Ning

2013-01-01

Background The efficacy of treatments that lower glucose in reducing the risk of incident stroke remains unclear. We therefore did a systematic review and meta-analysis to evaluate the efficacy of intensive control of glucose in the prevention of stroke. Methodology/Principal Findings We systematically searched Medline, EmBase, and the Cochrane Library for trials published between 1950 and June, 2012. We included randomized controlled trials that reported on the effects of intensive control of glucose on incident stroke compared with standard care. Summary estimates of relative risk (RR) reductions were calculated with a random effects model, and the analysis was further stratified by factors that could affect the treatment effects. Of 649 identified studies, we included nine relevant trials, which provided data for 59197 patients and 2037 events of stroke. Overall, intensive control of glucose as compared to standard care had no effect on incident stroke (RR, 0.96; 95%CI 0.88–1.06; P = 0.445). In the stratified analyses, a beneficial effect was seen in those trials when body mass index (BMI) more than 30 (RR, 0.86; 95%CI: 0.75–0.99; P = 0.041). No other significant differences were detected between the effect of intensive control of glucose and standard care when based on other subset factors. Conclusions/Significance Our study indicated intensive control of glucose can effectively reduce the risk of incident stroke when patients with BMI more than 30. PMID:23372729

Three randomized trials of maternal influenza immunization in Mali, Nepal, and South Africa: Methods and expectations.

PubMed

Omer, Saad B; Richards, Jennifer L; Madhi, Shabir A; Tapia, Milagritos D; Steinhoff, Mark C; Aqil, Anushka R; Wairagkar, Niteen

2015-07-31

Influenza infection in pregnancy can have adverse impacts on maternal, fetal, and infant outcomes. Influenza vaccination in pregnancy is an appealing strategy to protect pregnant women and their infants. The Bill & Melinda Gates Foundation is supporting three large, randomized trials in Nepal, Mali, and South Africa evaluating the efficacy and safety of maternal immunization to prevent influenza disease in pregnant women and their infants <6 months of age. Results from these individual studies are expected in 2014 and 2015. While the results from the three maternal immunization trials are likely to strengthen the evidence base regarding the impact of influenza immunization in pregnancy, expectations for these results should be realistic. For example, evidence from previous influenza vaccine studies - conducted in general, non-pregnant populations - suggests substantial geographic and year-to-year variability in influenza incidence and vaccine efficacy/effectiveness. Since the evidence generated from the three maternal influenza immunization trials will be complementary, in this paper we present a side-by-side description of the three studies as well as the similarities and differences between these trials in terms of study location, design, outcome evaluation, and laboratory and epidemiological methods. We also describe the likely remaining knowledge gap after the results from these trials become available along with a description of the analyses that will be conducted when the results from these individual data are pooled. Moreover, we highlight that additional research on logistics of seasonal influenza vaccine supply, surveillance and strain matching, and optimal delivery strategies for pregnant women will be important for informing global policy related to maternal influenza immunization. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Music for medical indications in the neonatal period: a systematic review of randomised controlled trials.

PubMed

Hartling, L; Shaik, M S; Tjosvold, L; Leicht, R; Liang, Y; Kumar, M

2009-09-01

To conduct a systematic review of the efficacy of music for medical indications in term or preterm neonates. We searched 17 electronic databases, subject bibliographies, reference lists and trials registries. Two reviewers independently screened studies for inclusion, assessed methodological quality, and extracted data. Meta-analysis was not feasible due to heterogeneity in outcomes so a qualitative analysis is presented. Nine randomised trials were included. The methodological quality was generally poor (median Jadad score = 1). The outcomes most commonly reported were physiological measures (heart rate (HR), respiratory rate, oxygen saturation (SaO2)), behavioural state and pain. Six studies evaluated music for the painful procedures circumcision (three trials) and heel prick (three trials). For circumcisions, one high quality pilot study (n = 23) showed benefits of music for the outcomes of HR, SaO2 and pain, while two low quality studies showed no difference. For heel prick, three low quality studies provided some evidence that music may be beneficial primarily for measures of behaviour and pain. The remaining studies evaluated the use of music in preterm infants to improve physiological and behavioural parameters (n = 31; benefits observed for behavioural parameters), to reinforce non-nutritive sucking via use of a pacifier activated lullaby (n = 32; significant increase in feeding rates), and to influence physiological stability and behaviours in infants with chronic lung disease (n = 22; no significant differences for outcomes assessed). The heterogeneity in study populations, interventions and outcomes precludes definitive conclusions around efficacy. There is preliminary evidence for some therapeutic benefits of music for specific indications; however, these findings need to be confirmed in methodologically rigorous trials.

Hyperbaric oxygen for neurologic indications--action plan for multicenter trials in: stroke, traumatic brain injury, radiation encephalopathy & status migrainosus.

PubMed

Helms, A; Evans, A W; Chu, J; Sahgal, A; Ostrowski, R; Sosiak, T; Wolf, G; Gillett, J; Whelan, H

2011-01-01

The 2008 Toronto Hyperbaric Medicine Symposium was convened to discuss research into neurologic indications for hyperbaric oxygen therapy (HBO2T). Four topics were particularly addressed: acute ischemic stroke; acute traumatic brain injury; brain radiation necrosis; and status migrainosus. Four multicenter trials were designed and proposed to evaluate the efficacy of HBO2T for these indications and are presented here in addition to brief reviews of the rationale behind each.

CLINICAL EVALUATION OF SAHACHARADI AND NIRGUNDI TAILAS IN SAISAVEEYAVATA (POLIOMYELITIS)

PubMed Central

Nair, P. Ramachandran; Vijayan, N. P.; Madhavikutty, P.; Nair, C. N. B.; Chandrika, A.

1988-01-01

A research trial was conducted at in-patient level to compare the efficacy of Sahacharadi taila with that of Nirgundi taila in Saisaveeyavata (Poliomyelitis). Forty cases were selected for the trial and grouped into two at random and treated with Sahacharadi taila and Nirgundi taila respectively. Results in both groups were highly encouraging and statistically significant. The study also revealed that 25% of patients had undergone Polio vaccination and it was not helpful to prevent the disease. PMID:22557625

Emerging Minimally Invasive Treatment Options for Male Lower Urinary Tract Symptoms.

PubMed

Magistro, Giuseppe; Chapple, Christopher R; Elhilali, Mostafa; Gilling, Peter; McVary, Kevin T; Roehrborn, Claus G; Stief, Christian G; Woo, Henry H; Gratzke, Christian

2017-12-01

Lower urinary tract symptoms (LUTS) are one of the most common and troublesome nonmalignant conditions affecting quality of life in aging men. A spectrum of established medical and surgical options is available to provide relief of bothersome LUTS. Both the adverse events of medication and the morbidity with surgical treatment modalities have to be counterbalanced against efficacy. Novel minimally invasive treatment options aim to be effective, ideally to be performed in an ambulatory setting under local anaesthesia and to offer a more favourable safety profile than existing reference techniques. A comprehensive, narrative review of novel minimally invasive treatment modalities for the management of male LUTS due to benign prostatic enlargement is presented. Medline, PubMed, Cochrane database, and Embase were screened for randomised controlled trials (RCTs), clinical trials, and reviews on novel minimally invasive treatment options for male LUTS due to benign prostatic enlargement. With regard to newly devised intraprostatic injectables (botulinum neurotoxin A, NX1207, PRX302), PRX302 is currently the only substance that was superior to placebo in a phase 3 RCT providing proof of efficacy and safety. The prostatic urethral lift technique has been evaluated in several phase 3 trials showing rapid and durable relief of LUTS without compromising sexual function in carefully selected patients without a prominent median lobe. The first clinical experience of the temporary implantable nitinol device demonstrated that implantation of this novel device is a safe procedure, easy, and fast to perform. Further studies are required to evaluate efficacy, durability, and to define appropriate patient selection. New ablative approaches like the image guided robotic waterjet ablation (AquaBeam) or procedures based on convective water vapour energy (Rezūm) are in the early stages of development. Prostatic artery embolization performed by interventional radiologists at specialised centres shows a high technical success rate in the treatment of bothersome LUTS. However, a substantial clinical failure rate and a particular spectrum of complications not commonly seen after urologic interventions do occur and need to be critically evaluated. Initial promising clinical results on novel minimally invasive treatment options indicate efficacy comparable to standard techniques, often associated with a more favourable safety profile, in particular with preservation of sexual function. Many of these techniques are in their infancy and based on experience of new developments in the past. Further RCTs are required to evaluate efficacy, safety, and durability of novel techniques with long-term follow-up and careful evaluation of the selection criteria, which have been applied in clinical trials. The prostatic urethral lift is the only procedure with Level 1 evidence data and that can therefore be recommended for treatment of male LUTS in clinical practice for selected patients. Minimally invasive treatment options have been developed to provide relief of lower urinary tract symptoms comparable to standard surgical techniques with a more favourable safety profile. However, long-term clinical evaluation is still needed for most of these innovations before they can be recommended to be an effective replacement for standard surgical treatment. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Efficacy of customised foot orthoses in the treatment of Achilles tendinopathy: study protocol for a randomised trial

PubMed Central

Munteanu, Shannon E; Landorf, Karl B; Menz, Hylton B; Cook, Jill L; Pizzari, Tania; Scott, Lisa A

2009-01-01

Background Achilles tendinopathy is a common condition that can cause marked pain and disability. Numerous non-surgical treatments have been proposed for the treatment of this condition, but many of these treatments have a poor or non-existent evidence base. The exception to this is eccentric calf muscle exercises, which have become a standard non-surgical intervention for Achilles tendinopathy. Foot orthoses have also been advocated as a treatment for Achilles tendinopathy, but the long-term efficacy of foot orthoses for this condition is unknown. This manuscript describes the design of a randomised trial to evaluate the efficacy of customised foot orthoses to reduce pain and improve function in people with Achilles tendinopathy. Methods One hundred and forty community-dwelling men and women aged 18 to 55 years with Achilles tendinopathy (who satisfy inclusion and exclusion criteria) will be recruited. Participants will be randomised, using a computer-generated random number sequence, to either a control group (sham foot orthoses made from compressible ethylene vinyl acetate foam) or an experimental group (customised foot orthoses made from semi-rigid polypropylene). Both groups will be prescribed a calf muscle eccentric exercise program, however, the primary difference between the groups will be that the experimental group receive customised foot orthoses, while the control group receive sham foot orthoses. The participants will be instructed to perform eccentric exercises 2 times per day, 7 days per week, for 12 weeks. The primary outcome measure will be the total score of the Victorian Institute of Sport Assessment - Achilles (VISA-A) questionnaire. The secondary outcome measures will be participant perception of treatment effect, comfort of the foot orthoses, use of co-interventions, frequency and severity of adverse events, level of physical activity and health-related quality of life (assessed using the Short-Form-36 questionnaire - Version two). Data will be collected at baseline, then at 1, 3, 6 and 12 months. Data will be analysed using the intention to treat principle. Discussion This study is the first randomised trial to evaluate the long-term efficacy of customised foot orthoses for the treatment of Achilles tendinopathy. The study has been pragmatically designed to ensure that the study findings are generalisable to clinical practice. Trial registration Australian New Zealand Clinical Trials Registry Number: ACTRN12609000829213. PMID:19852853

Oral ondansetron versus domperidone for symptomatic treatment of vomiting during acute gastroenteritis in children: multicentre randomized controlled trial.

PubMed

Marchetti, Federico; Maestro, Alessandra; Rovere, Francesca; Zanon, Davide; Arrighini, Alberto; Bertolani, Paolo; Biban, Paolo; Da Dalt, Liviana; Di Pietro, Pasquale; Renna, Salvatore; Guala, Andrea; Mannelli, Francesco; Pazzaglia, Anna; Messi, Gianni; Perri, Francesco; Reale, Antonino; Urbino, Antonio Francesco; Valletta, Enrico; Vitale, Antonio; Zangardi, Tiziana; Tondelli, Maria Teresa; Clavenna, Antonio; Bonati, Maurizio; Ronfani, Luca

2011-02-10

Vomiting in children with acute gastroenteritis (AG) is not only a direct cause of fluid loss but it is also a major factor of failure of oral rehydration therapy (ORT). Physicians who provide care to paediatric patients in the emergency department (ED) usually prescribe intravenous fluid therapy (IVT) for mild or moderate dehydration when vomiting is the major symptom. Thus, effective symptomatic treatment of vomiting would lead to an important reduction in the use of IVT and, consequently, of the duration of hospital stay and of frequency of hospital admission. Available evidence on symptomatic treatment of vomiting shows the efficacy of the most recently registered molecule (ondansetron) but a proper evaluation of antiemetics drugs largely used in clinical practice, such as domperidone, is lacking. To compare the efficacy of ondansetron and domperidone for the symptomatic treatment of vomiting in children with AG who have failed ORT. Multicentre, double-blind randomized controlled trial conducted in paediatric EDs. Children aged from 1 to 6 years who vomiting, with a presumptive clinical diagnosis of AG, and without severe dehydration will be included. After the failure of a initial ORS administration in ED, eligible children will be randomized to receive: 1) ondansetron syrup (0,15 mg/Kg of body weight); 2) domperidone syrup (0,5 mg/Kg of body weight); 3) placebo. The main study outcome will be the percentage of patients needing nasogastric or IVT after symptomatic oral treatment failure, defined as vomiting or fluid refusal after a second attempt of ORT. Data relative to study outcomes will be collected at 30 minute intervals for a minimum of 6 hours. A telephone follow up call will be made 48 hours after discharge. A total number of 540 children (i.e. 180 patients in each arm) will be enrolled. The trial results would provide evidence on the efficacy of domperidone, which is largely used in clinical practice despite the lack of proper evaluation and a controversial safety profile, as compared to ondansetron, which is not yet authorized in Italy despite evidence supporting its efficacy in treating vomiting. The trial results would contribute to a reduction in the use of IVT and, consequently, in hospital admissions in children with AG. The design of this RCT, which closely reflect current clinical practice in EDs, will allow immediate transferability of results. ClinicalTrials.gov: NCT01257672.

The comparative evidence basis for the efficacy of second-generation antidepressants in the treatment of depression in the US: A Bayesian meta-analysis of Food and Drug Administration reviews.

PubMed

Monden, Rei; Roest, Annelieke M; van Ravenzwaaij, Don; Wagenmakers, Eric-Jan; Morey, Richard; Wardenaar, Klaas J; de Jonge, Peter

2018-08-01

Studies have shown similar efficacy of different antidepressants in the treatment of depression. Data of phase-2 and -3 clinical-trials for 16 antidepressants (levomilnacipran, desvenlafaxine, duloxetine, venlafaxine, paroxetine, escitalopram, vortioxetine, mirtazapine, venlafaxine XR, sertraline, fluoxetine, citalopram, paroxetine CR, nefazodone, bupropion, vilazodone), approved by the FDA for the treatment of depression between 1987 and 2016, were extracted from the FDA reviews that were used to evaluate efficacy prior to marketing approval, which are less liable to reporting biases. Meta-analytic Bayes factors, which quantify the strength of evidence for efficacy, were calculated. In addition, posterior pooled effect-sizes were calculated and compared with classical estimations. The resulted Bayes factors showed that the evidence load for efficacy varied strongly across antidepressants. However, all tested drugs except for bupropion and vilazodone showed strong evidence for their efficacy. The posterior effect-size distributions showed variation across antidepressants, with the highest pooled estimated effect size for venlafaxine followed by paroxetine, and the lowest for bupropion and vilazodone. Not all published trials were included in the study. The results illustrate the importance of considering both the effect size and the evidence-load when judging the efficacy of a treatment. In doing so, the currently employed Bayesian approach provided clear insights on top of those gained with traditional approaches. Copyright © 2018 Elsevier B.V. All rights reserved.

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Reiss, Ulrike M

2016-12-20

Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. This is an update of a published Cochrane Review. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 18 August 2016. Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: A meta-analysis

PubMed Central

Li, Li; Tao, Sun; Bo, Lin; Lin, Chen

2017-01-01

Purpose The aim of this study was to evaluate the therapeutic efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of patients with knee osteoarthritis (OA). Materials We performed a meta-analysis of relevant published clinical studies. An electronic search was conducted for randomized controlled trials (RCTs) of MSC-based therapy in knee OA. The visual analogue scale (VAS), International Knee Documentation Committee (IKDC) form, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne algofunctional indices (Lequesne), Lysholm knee scale (Lysholm), Tegner activity scale (Tegner) and adverse events (AEs) were evaluated. Results Eleven eligible trials with 582 knee OA patients were included in the present meta-analysis. We demonstrated that MSC treatment could significantly decrease VAS and increase IKDC scoresafter a 24-month follow-up compared with controls (P<0.05). MSC therapy also showed significant decreases in WOMAC and Lequesne scores after the 12-month follow-up (P<0.01). Analysis of Lysholm (24-month) and Tegner (12- and 24-month) scores also demonstrated favorable results for MSC treatment (P<0.05). Conclusion Overall, MSC transplantation treatment was shown to be safe and has great potential as an efficacious clinical therapy for patients with knee OA. PMID:28448518

Advances in the treatment of invasive neonatal candidiasis

PubMed Central

Botero-Calderon, Lorena; Benjamin, Daniel K.; Cohen-Wolkowiez, Michael

2015-01-01

Introduction Invasive candidiasis is responsible for approximately 10% of nosocomial sepsis in very-low-birth-weight (VLBW) infants and is associated with substantial morbidity and mortality. Over the last 2 decades, the antifungal armamentarium against Candida spp. has increased; however, efficacy and safety studies in this population are lacking. Areas covered We reviewed the medical literature and extracted information on clinical and observational studies evaluating the use of antifungal agents in neonates with invasive candidiasis. Expert opinion Efficacy and safety data for antifungals in neonates are lacking, and the majority of studies conducted to date have concentrated on pharmacokinetic/pharmacodynamic evaluations. Unlike other anti-infective agents, efficacy data in the setting of neonatal candidiasis cannot be extrapolated from adult studies due to differences in the pathophysiology of the disease in this population relative to older children and adults. Data collected thus far or data submitted to regulatory agencies for amphotericin B deoxycholate, fluconazole, and micafungin suggest that these are the current agents of choice for this disease in neonates until data for newer antifungal agents become available. For prophylaxis, data from fluconazole randomized controlled trials will be submitted to the regulatory agencies for labeling. Ultimately, the field of therapeutics for neonatal candidiasis will require multidisciplinary collaboration given the numerous challenges associated with conducting clinical trials in neonates. PMID:25842986