Reliability of surface electromyography activity of gluteal and hamstring muscles during sub-maximal and maximal voluntary isometric contractions.

PubMed

Bussey, Melanie D; Aldabe, Daniela; Adhia, Divya; Mani, Ramakrishnan

2018-04-01

Normalizing to a reference signal is essential when analysing and comparing electromyography signals across or within individuals. However, studies have shown that MVC testing may not be as reliable in persons with acute and chronic pain. The purpose of this study was to compare the test-retest reliability of the muscle activity in the biceps femoris and gluteus maximus between a novel sub-MVC and standard MVC protocols. This study utilized a single individual repeated measures design with 12 participants performing multiple trials of both the sub-MVC and MVC tasks on two separate days. The participant position in the prone leg raise task was standardised with an ultrasonic sensor to improve task precession between trials/days. Day-to-day and trial-to-trial reliability of the maximal muscle activity was examined using ICC and SEM. Day-to-day and trial-to-trial reliability of the EMG activity in the BF and GM were high (0.70-0.89) to very high (≥0.90) for both test procedures. %SEM was <5-10% for both tests on a given day but higher in the day-to-day comparisons. The lower amplitude of the sub-MVC is a likely contributor to increased %SEM (8-13%) in the day-to-day comparison. The findings show that the sub-MVC modified prone double leg raise results in GM and BF EMG measures similar in reliability and precision to the standard MVC tasks. Therefore, the modified prone double leg raise may be a useful substitute for traditional MVC testing for normalizing EMG signals of the BF and GM. Copyright © 2017 Elsevier Ltd. All rights reserved.

The application of active side arm controllers in helicopters

NASA Technical Reports Server (NTRS)

Knorr, R.; Melz, C.; Faulkner, A.; Obermayer, M.

1993-01-01

Eurocopter Deutschland (ECD) started simulation trials to investigate the particular problems of Side Arm Controllers (SAC) applied to helicopters. Two simulation trials have been performed. In the first trial, the handling characteristics of a 'passive' SAC and the basic requirements for the application of an 'active' SAC were evaluated in pilot-in-the-loop simulations, performing the tasks in a realistic scenario representing typical phases of a transport mission. The second simulation trial investigated the general control characteristics of the 'active' in comparison to the 'passive' control principle. A description of the SACs developed by ECD and the principle of the 'passive' and 'active' control concept is given, as well as specific ratings for the investigated dynamic and ergonomic parameters effecting SAC characteristics. The experimental arrangements, as well as the trials procedures of both simulation phases, are described and the results achieved are discussed emphasizing the advantages of the 'active' as opposed to the 'passive' SAC concept. This also includes the presentation of some critical aspects still to be improved and proposals to solve them.

Multisite Randomized Trial of Behavioral Interventions for Women with Co-Occurring PTSD and Substance Use Disorders

ERIC Educational Resources Information Center

Hien, Denise A.; Wells, Elizabeth A.; Jiang, Huiping; Suarez-Morales, Lourdes; Campbell, Aimee N. C.; Cohen, Lisa R.; Miele, Gloria M.; Killeen, Therese; Brigham, Gregory S.; Zhang, Yulei; Hansen, Cheri; Hodgkins, Candace; Hatch-Maillette, Mary; Brown, Chanda; Kulaga, Agatha; Kristman-Valente, Allison; Chu, Melissa; Sage, Robert; Robinson, James A.; Liu, David; Nunes, Edward V.

2009-01-01

The authors compared the effectiveness of the Seeking Safety group, cognitive-behavioral treatment for substance use disorder and posttraumatic stress disorder (PTSD), to an active comparison health education group (Women's Health Education [WHE]) within the National Institute on Drug Abuse's Clinical Trials Network. The authors randomized 353…

The ethics of placebo-controlled trials: a comparison of inert and active placebo controls.

PubMed

Edward, Sarah J L; Stevens, Andrew J; Braunholtz, David A; Lilford, Richard J; Swift, Teresa

2005-05-01

Because of the recent and controversial example of sham surgery for the evaluation of fetal tissue transplants for Parkinson's disease, there is renewed interest in the ethics of using "active" placebos in surgical trials, where otherwise there are no inert procedures available, and in pharmacological trials, where there are inert substances, but where patients may guess to which arm they have been allocated. This paper seeks to clarify the ethical arguments surrounding the use of active placebos in trials, and to set up a notation for assessing the ethics of trials more generally. We first establish an framework by which ethics committees can analyze such trials. We examine (1) the scientific value of the research; (2) the expected risks and benefits to individual patients, and (3) the voluntary nature of consent. We then contrast the implications of this framework for inert and active placebo-controlled trials, respectively. In particular, we analyze their relative expected utility using three main utility factors, namely, treatment effects, placebo effects, and altruism. We conclude that, when the intervention is already widely available, active placebo trials rely more heavily on altruism than do inert placebo trials and, when the intervention is restricted, this excess reliance may not be needed. What our analysis provides is the explicit justification for the apparent caution of Institutional Review Boards or ethics committees when reviewing sham operations, especially when the expected harm is not trivial and the risk of exploitation is high.

Physical and psychologic effects of aromatherapy inhalation on pregnant women: a randomized controlled trial.

PubMed

Igarashi, Toshiko

2013-10-01

Stress reduction care is important for pregnant women to decrease obstetric complications and children's health problems after birth. The aim of this study is to clarify the physical and psychologic effects of inhalation aromatherapy on pregnant women. Essential oils with high linalool and linalyl acetate content that may be used during pregnancy were selected and among these, and the one preferred by the participant was used. This was a prospective, randomized, controlled trial. This trial was performed at a gynecology outpatient department in a hospital in Kyoto, Japan. The study included pregnant women in week 28 of a single pregnancy with a normal course. Participants were randomly assigned into an aromatherapy group and a control group. They were seated in the resting, seated position for 10 minutes. During the latter 5 minutes of each 10-minute session, aromatherapy inhalation was performed for the aromatherapy group. Before and after the intervention, the Profile of Mood States (POMS) was measured. During the trial, the heart-rate fluctuations were measured for the autonomic nervous system regulation. A total of 13 pregnant women participated in the trial. Seven (7) participants were assigned to the aromatherapy group and 6 participants to the control group. The results of the POMS were such that based on an intragroup comparison, significant differences were observed in the Tension-Anxiety score (p<0.05) and the Anger-Hostility score (p<0.05), and the respective improvements observed were due to aromatherapy. The results of the autonomic nervous system regulation were such that based on an intragroup comparison within the aromatherapy group, the parasympathetic nerve activity increased significantly (p<0.05). Aromatherapy inhalation using essential oils containing linalyl acetate and linalool was found to be effective for the POMS and parasympathetic nerve activity, based on an intragroup comparison. However, based on a comparison between the groups, no substantial difference was observed; hence, further study is necessary in the future.

Pelvic floor muscle training added to another active treatment versus the same active treatment alone for urinary incontinence in women.

PubMed

Ayeleke, Reuben Olugbenga; Hay-Smith, E Jean C; Omar, Muhammad Imran

2015-11-03

Pelvic floor muscle training (PFMT) is a first-line conservative treatment for urinary incontinence in women. Other active treatments include: physical therapies (e.g. vaginal cones); behavioural therapies (e.g. bladder training); electrical or magnetic stimulation; mechanical devices (e.g. continence pessaries); drug therapies (e.g. anticholinergics (solifenacin, oxybutynin, etc.) and duloxetine); and surgical interventions including sling procedures and colposuspension. This systematic review evaluated the effects of adding PFMT to any other active treatment for urinary incontinence in women To compare the effects of pelvic floor muscle training combined with another active treatment versus the same active treatment alone in the management of women with urinary incontinence. We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 5 May 2015), and CINAHL (January 1982 to 6 May 2015), and the reference lists of relevant articles. We included randomised or quasi-randomised trials with two or more arms, of women with clinical or urodynamic evidence of stress urinary incontinence, urgency urinary incontinence or mixed urinary incontinence. One arm of the trial included PFMT added to another active treatment; the other arm included the same active treatment alone. Two review authors independently assessed trials for eligibility and methodological quality and resolved any disagreement by discussion or consultation with a third party. We extracted and processed data in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Other potential sources of bias we incorporated into the 'Risk of bias' tables were ethical approval, conflict of interest and funding source. Thirteen trials met the inclusion criteria, comprising women with stress urinary incontinence (SUI), urgency urinary incontinence (UUI) or mixed urinary incontinence (MUI); they compared PFMT added to another active treatment (585 women) with the same active treatment alone (579 women). The pre-specified comparisons were reported by single trials, except bladder training, which was reported by two trials, and electrical stimulation, which was reported by three trials. However, only two of the three trials reporting electrical stimulation could be pooled, as one of the trials did not report any relevant data. We considered the included trials to be at unclear risk of bias for most of the domains, predominantly due to the lack of adequate information in a number of trials. This affected our rating of the quality of evidence. The majority of the trials did not report the primary outcomes specified in the review (cure or improvement, quality of life) or measured the outcomes in different ways. Effect estimates from small, single trials across a number of comparisons were indeterminate for key outcomes relating to symptoms, and we rated the quality of evidence, using the GRADE approach, as either low or very low. More women reported cure or improvement of incontinence in two trials comparing PFMT added to electrical stimulation to electrical stimulation alone, in women with SUI, but this was not statistically significant (9/26 (35%) versus 5/30 (17%); risk ratio (RR) 2.06, 95% confidence interval (CI) 0.79 to 5.38). We judged the quality of the evidence to be very low. There was moderate-quality evidence from a single trial investigating women with SUI, UUI or MUI that a higher proportion of women who received a combination of PFMT and heat and steam generating sheet reported a cure compared to those who received the sheet alone: 19/37 (51%) versus 8/37 (22%) with a RR of 2.38, 95% CI 1.19 to 4.73). More women reported cure or improvement of incontinence in another trial comparing PFMT added to vaginal cones to vaginal cones alone, but this was not statistically significant (14/15 (93%) versus 14/19 (75%); RR 1.27, 95% CI 0.94 to 1.71). We judged the quality of the evidence to be very low. Only one trial evaluating PFMT when added to drug therapy provided information about adverse events (RR 0.84, 95% CI 0.45 to 1.60; very low-quality evidence).With regard to condition-specific quality of life, there were no statistically significant differences between women (with SUI, UUI or MUI) who received PFMT added to bladder training and those who received bladder training alone at three months after treatment, on either the Incontinence Impact Questionnaire-Revised scale (mean difference (MD) -5.90, 95% CI -35.53 to 23.73) or on the Urogenital Distress Inventory scale (MD -18.90, 95% CI -37.92 to 0.12). A similar pattern of results was observed between women with SUI who received PFMT plus either a continence pessary or duloxetine and those who received the continence pessary or duloxetine alone. In all these comparisons, the quality of the evidence for the reported critical outcomes ranged from moderate to very low. This systematic review found insufficient evidence to state whether or not there were additional effects by adding PFMT to other active treatments when compared with the same active treatment alone for urinary incontinence (SUI, UUI or MUI) in women. These results should be interpreted with caution as most of the comparisons were investigated in small, single trials. None of the trials in this review were large enough to provide reliable evidence. Also, none of the included trials reported data on adverse events associated with the PFMT regimen, thereby making it very difficult to evaluate the safety of PFMT.

Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial

PubMed Central

2012-01-01

Background Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological and practical issues arising with (1) stopping recruitment to research arms following a pre-planned intermediate analysis and (2) adding a new research arm during the trial. Methods STAMPEDE recruits men who have locally advanced or metastatic prostate cancer who are starting standard long-term hormone therapy. Originally there were five research and one control arms, each undergoing a pilot stage (focus: safety, feasibility), three intermediate ‘activity’ stages (focus: failure-free survival), and a final ‘efficacy’ stage (focus: overall survival). Lack-of-sufficient-activity guidelines support the pairwise interim comparisons of each research arm against the control arm; these pre-defined activity cut-off becomes increasingly stringent over the stages. Accrual of further patients continues to the control arm and to those research arms showing activity and an acceptable safety profile. The design facilitates adding new research arms should sufficiently interesting agents emerge. These new arms are compared only to contemporaneously recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is subject to adequate recruitment rates to support the overall trial aims. Results (1) Stopping Existing Therapy: After the second intermediate activity analysis, recruitment was discontinued to two research arms for lack-of-sufficient activity. Detailed preparations meant that changes were implemented swiftly at 100 international centers and recruitment continued seamlessly into Activity Stage III with 3 remaining research arms and the control arm. Further regulatory and ethical approvals were not required because this was already included in the initial trial design. (2) Adding New Therapy: An application to add a new research arm was approved by the funder, (who also organized peer review), industrial partner and regulatory and ethical bodies. This was all done in advance of any decision to stop current therapies. Conclusions The STAMPEDE experience shows that recruitment to a MAMS trial and mid-flow changes its design are achievable with good planning. This benefits patients and the scientific community as research treatments are evaluated in a more efficient and cost-effective manner. Trial registration ISRCTN78818544, NCT00268476 First patient into trial: 17 October 2005 First patient into abiraterone comparison: 15 November 2011 PMID:22978443

Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial.

PubMed

Sydes, Matthew R; Parmar, Mahesh K B; Mason, Malcolm D; Clarke, Noel W; Amos, Claire; Anderson, John; de Bono, Johann; Dearnaley, David P; Dwyer, John; Green, Charlene; Jovic, Gordana; Ritchie, Alastair W S; Russell, J Martin; Sanders, Karen; Thalmann, George; James, Nicholas D

2012-09-15

Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological and practical issues arising with (1) stopping recruitment to research arms following a pre-planned intermediate analysis and (2) adding a new research arm during the trial. STAMPEDE recruits men who have locally advanced or metastatic prostate cancer who are starting standard long-term hormone therapy. Originally there were five research and one control arms, each undergoing a pilot stage (focus: safety, feasibility), three intermediate 'activity' stages (focus: failure-free survival), and a final 'efficacy' stage (focus: overall survival). Lack-of-sufficient-activity guidelines support the pairwise interim comparisons of each research arm against the control arm; these pre-defined activity cut-off becomes increasingly stringent over the stages. Accrual of further patients continues to the control arm and to those research arms showing activity and an acceptable safety profile. The design facilitates adding new research arms should sufficiently interesting agents emerge. These new arms are compared only to contemporaneously recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is subject to adequate recruitment rates to support the overall trial aims. (1) Stopping Existing Therapy: After the second intermediate activity analysis, recruitment was discontinued to two research arms for lack-of-sufficient activity. Detailed preparations meant that changes were implemented swiftly at 100 international centers and recruitment continued seamlessly into Activity Stage III with 3 remaining research arms and the control arm. Further regulatory and ethical approvals were not required because this was already included in the initial trial design.(2) Adding New Therapy: An application to add a new research arm was approved by the funder, (who also organized peer review), industrial partner and regulatory and ethical bodies. This was all done in advance of any decision to stop current therapies. The STAMPEDE experience shows that recruitment to a MAMS trial and mid-flow changes its design are achievable with good planning. This benefits patients and the scientific community as research treatments are evaluated in a more efficient and cost-effective manner. ISRCTN78818544, NCT00268476. First patient into trial: 17 October 2005. First patient into abiraterone comparison: 15 November 2011.

Effect of cocoa on blood pressure.

PubMed

Ried, Karin; Fakler, Peter; Stocks, Nigel P

2017-04-25

High blood pressure is an important risk factor for cardiovascular disease, contributing to about 50% of cardiovascular events worldwide and 37% of cardiovascular-related deaths in Western populations. Epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. Flavanols found in cocoa have been shown to increase the formation of endothelial nitric oxide which promotes vasodilation and therefore blood pressure reduction. Here we update previous meta-analyses on the effect of cocoa on blood pressure. To assess the effects on blood pressure of chocolate or cocoa products versus low-flavanol products or placebo in adults with or without hypertension when consumed for two weeks or longer. This is an updated version of the review initially published in 2012. In this updated version, we searched the following electronic databases from inception to November 2016: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE and Embase. We also searched international trial registries, and the reference lists of review articles and included trials. Randomised controlled trials (RCTs) investigating the effects of chocolate or cocoa products on systolic and diastolic blood pressure in adults for a minimum of two weeks duration. Two review authors independently extracted data and assessed the risks of bias in each trial. We conducted random-effects meta-analyses on the included studies using Review Manager 5. We explored heterogeneity with subgroup analyses by baseline blood pressure, flavanol content of control group, blinding, age and duration. Sensitivity analyses explored the influence of unusual study design. Thirty-five trials (including 40 treatment comparisons) met the inclusion criteria. Of these, we added 17 trials (20 treatment comparisons) to the 18 trials (20 treatment comparisons) in the previous version of this updated review.Trials provided participants with 30 to 1218 mg of flavanols (mean = 670 mg) in 1.4 to 105 grams of cocoa products per day in the active intervention group. The control group received either a flavanol-free product (n = 26 treatment comparisons) or a low-flavanol-containing cocoa powder (range 6.4 to 88 mg flavanols (mean = 55 mg, 13 treatment comparisons; 259 mg, 1 trial).Meta-analyses of the 40 treatment comparisons involving 1804 mainly healthy participants revealed a small but statistically significant blood pressure-reducing effect of flavanol-rich cocoa products compared with control in trials of two to 18 weeks duration (mean nine weeks):Mean difference systolic blood pressure (SBP) (95% confidence interval (CI): -1.76 (-3.09 to -0.43) mmHg, P = 0.009, n = 40 treatment comparisons, 1804 participants;Mean difference diastolic blood pressure (DBP) (95% CI): -1.76 (-2.57 to -0.94) mmHg, P < 0.001, n = 39 treatment comparisons, 1772 participants.Baseline blood pressure may play a role in the effect of cocoa on blood pressure. While systolic blood pressure was reduced significantly by 4 mmHg in hypertensive people (n = 9 treatment comparisons, 401 participants), and tended to be lowered in prehypertensive people (n= 8 treatment comparisons, 340 participants), there was no significant difference in normotensive people (n = 23 treatment comparisons, 1063 participants); however, the test for subgroup differences was of borderline significance (P = 0.08; I 2 = 60%), requiring further research to confirm the findings.Subgroup meta-analysis by blinding suggested a trend towards greater blood pressure reduction in unblinded trials compared to double-blinded trials, albeit statistically not significant. Further research is needed to confirm whether participant expectation may influence blood pressure results. Subgroup analysis by type of control (flavanol-free versus low-flavanol control) did not reveal a significant difference.Whether the age of participants plays a role in the effect of cocoa on blood pressure, with younger participants responding with greater blood pressure reduction, needs to be further investigated.Sensitivity analysis excluding trials with authors employed by trials sponsoring industry (33 trials, 1482 participants) revealed a small reduction in effect size, indicating some reporting bias.Due to the remaining heterogeneity, which we could not explain in terms of blinding, flavanol content of the control groups, age of participants, or study duration, we downgraded the quality of the evidence from high to moderate.Results of subgroup analyses should be interpreted with caution and need to be confirmed or refuted in trials using direct randomised comparisons.Generally, cocoa products were highly tolerable, with adverse effects including gastrointestinal complaints and nausea being reported by 1% of participants in the active cocoa intervention group and 0.4% of participants in the control groups (moderate-quality evidence). This review provides moderate-quality evidence that flavanol-rich chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering effect in mainly healthy adults in the short term.These findings are limited by the heterogeneity between trials, which could not be explained by prespecified subgroup analyses, including blinding, flavanol content of the control groups, age of participants, or study duration. However, baseline blood pressure may play a role in the effect of cocoa on blood pressure; subgroup analysis of trials with (pre)hypertensive participants revealed a greater blood pressure-reducing effect of cocoa compared to normotensive participants with borderline significance.Long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products.

Therapeutic Drug Monitoring of Asparaginase Activity-Method Comparison of MAAT and AHA Test Used in the International AIEOP-BFM ALL 2009 Trial.

PubMed

Lanvers-Kaminsky, Claudia; Rüffer, Andrea; Würthwein, Gudrun; Gerss, Joachim; Zucchetti, Massimo; Ballerini, Andrea; Attarbaschi, Andishe; Smisek, Petr; Nath, Christa; Lee, Samiuela; Elitzur, Sara; Zimmermann, Martin; Möricke, Anja; Schrappe, Martin; Rizzari, Carmelo; Boos, Joachim

2018-02-01

In the international AIEOP-BFM ALL 2009 trial, asparaginase (ASE) activity was monitored after each dose of pegylated Escherichia coli ASE (PEG-ASE). Two methods were used: the aspartic acid β-hydroxamate (AHA) test and medac asparaginase activity test (MAAT). As the latter method overestimates PEG-ASE activity because it calibrates using E. coli ASE, method comparison was performed using samples from the AIEOP-BFM ALL 2009 trial. PEG-ASE activities were determined using MAAT and AHA test in 2 sets of samples (first set: 630 samples and second set: 91 samples). Bland-Altman analysis was performed on ratios between MAAT and AHA tests. The mean difference between both methods, limits of agreement, and 95% confidence intervals were calculated and compared for all samples and samples grouped according to the calibration ranges of the MAAT and the AHA test. PEG-ASE activity determined using the MAAT was significantly higher than when determined using the AHA test (P < 0.001; Wilcoxon signed-rank test). Within the calibration range of the MAAT (30-600 U/L), PEG-ASE activities determined using the MAAT were on average 23% higher than PEG-ASE activities determined using the AHA test. This complies with the mean difference reported in the MAAT manual. With PEG-ASE activities >600 U/L, the discrepancies between MAAT and AHA test increased. Above the calibration range of the MAAT (>600 U/L) and the AHA test (>1000 U/L), a mean difference of 42% was determined. Because more than 70% of samples had PEG-ASE activities >600 U/L and required additional sample dilution, an overall mean difference of 37% was calculated for all samples (37% for the first and 34% for the second set). Comparison of the MAAT and AHA test for PEG-ASE activity confirmed a mean difference of 23% between MAAT and AHA test for PEG-ASE activities between 30 and 600 U/L. The discrepancy increased in samples with >600 U/L PEG-ASE activity, which will be especially relevant when evaluating high PEG-ASE activities in relation to toxicity, efficacy, and population pharmacokinetics.

Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions.

PubMed

Johns, Claire; Seav, Susan M; Dominick, Sally A; Gorman, Jessica R; Li, Hongying; Natarajan, Loki; Mao, Jun James; Irene Su, H

2016-04-01

Patient-centered decision making about hot flash treatments often incorporates a balance of efficacy and side effects in addition to patient preference. This systematic review examines randomized controlled trials (RCTs) comparing at least two non-hormonal hot flash treatments in breast cancer survivors. In July 2015, PubMed, SCOPUS, CINAHL, Cochrane, and Web of Science databases were searched for RCTs comparing active, non-hormonal hot flash treatments in female breast cancer survivors. Thirteen trials were included after identifying 906 potential studies. Four trials were dose comparison studies of pharmacologic treatments citalopram, venlafaxine, gabapentin, and paroxetine. Hot flash reduction did not differ by tamoxifen or aromatase inhibitor use. Citalopram 10, 20, and 30 mg daily had comparable outcomes. Venlafaxine 75 mg daily improved hot flashes without additional side effects from higher dosing. Gabapentin 900 mg daily improved hot flashes more than 300 mg. Paroxetine 10 mg daily had fewer side effects than 20 mg. Among four trials comparing different pharmacologic treatments, venlafaxine alleviated hot flash symptoms faster than clonidine; participants preferred venlafaxine over gabapentin. Five trials compared pharmacologic to non-pharmacologic treatments. Acupuncture had similar efficacy to venlafaxine and gabapentin but may have longer durability after completing treatment and fewer side effects. We could not perform a pooled meta-analysis because outcomes were not reported in comparable formats. Clinical trial data on non-hormonal hot flash treatments provide comparisons of hot flash efficacy and other patient important outcomes to guide clinical management. Clinicians can use the information to help patients select hot flash interventions.

Standardizing clinical trials workflow representation in UML for international site comparison.

PubMed

de Carvalho, Elias Cesar Araujo; Jayanti, Madhav Kishore; Batilana, Adelia Portero; Kozan, Andreia M O; Rodrigues, Maria J; Shah, Jatin; Loures, Marco R; Patil, Sunita; Payne, Philip; Pietrobon, Ricardo

2010-11-09

With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows.

Standardizing Clinical Trials Workflow Representation in UML for International Site Comparison

PubMed Central

de Carvalho, Elias Cesar Araujo; Jayanti, Madhav Kishore; Batilana, Adelia Portero; Kozan, Andreia M. O.; Rodrigues, Maria J.; Shah, Jatin; Loures, Marco R.; Patil, Sunita; Payne, Philip; Pietrobon, Ricardo

2010-01-01

Background With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. Methods Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. Results Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. Conclusions This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows. PMID:21085484

A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

PubMed

Bell, Stuart A; Tudur Smith, Catrin

2014-11-26

To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials.

PubMed

Massari, Francesco; Modena, Alessandra; Ciccarese, Chiara; Pilotto, Sara; Maines, Francesca; Bracarda, Sergio; Sperduti, Isabella; Giannarelli, Diana; Carlini, Paolo; Santini, Daniele; Tortora, Giampaolo; Porta, Camillo; Bria, Emilio

2016-02-01

We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations. An overall survival (OS) significant difference according to therapeutic strategy was more likely be determined in RCTs evaluating hormonal drugs versus those studies testing immunotherapy, chemotherapy or other strategies. With regard to control arm, an OS significant effect was found for placebo-controlled trials versus studies comparing experimental treatment with active therapies. Finally, regarding to docetaxel (DOC) timing, the OS benefit was more likely to be proved in Post-DOC setting in comparison with DOC and Pre-DOC. These data suggest that clinical trial design should take into account new benchmarks such as the type of treatment strategy, the choice of the comparator and the phase of the disease in relation to the administration of standard chemotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Active Inference, Epistemic Value, and Vicarious Trial and Error

ERIC Educational Resources Information Center

Pezzulo, Giovanni; Cartoni, Emilio; Rigoli, Francesco; io-Lopez, Léo; Friston, Karl

2016-01-01

Balancing habitual and deliberate forms of choice entails a comparison of their respective merits--the former being faster but inflexible, and the latter slower but more versatile. Here, we show that arbitration between these two forms of control can be derived from first principles within an Active Inference scheme. We illustrate our arguments…

Randomized clinical trial of bright light therapy for antepartum depression: preliminary findings.

PubMed

Epperson, C Neill; Terman, Michael; Terman, Jiuan Su; Hanusa, Barbara H; Oren, Dan A; Peindl, Kathleen S; Wisner, Katherine L

2004-03-01

Bright light therapy was shown to be a promising treatment for depression during pregnancy in a recent open-label study. In an extension of this work, we report findings from a double-blind placebo-controlled pilot study. Ten pregnant women with DSM-IV major depressive disorder were randomly assigned from April 2000 to January 2002 to a 5-week clinical trial with either a 7000 lux (active) or 500 lux (placebo) light box. At the end of the randomized controlled trial, subjects had the option of continuing in a 5-week extension phase. The Structured Interview Guide for the Hamilton Depression Scale-Seasonal Affective Disorder Version was administered to assess changes in clinical status. Salivary melatonin was used to index circadian rhythm phase for comparison with antidepressant results. Although there was a small mean group advantage of active treatment throughout the randomized controlled trial, it was not statistically significant. However, in the longer 10-week trial, the presence of active versus placebo light produced a clear treatment effect (p =.001) with an effect size (0.43) similar to that seen in antidepressant drug trials. Successful treatment with bright light was associated with phase advances of the melatonin rhythm. These findings provide additional evidence for an active effect of bright light therapy for antepartum depression and underscore the need for an expanded randomized clinical trial.

Efficacy of individualised diets in patients with irritable bowel syndrome: a randomised controlled trial

PubMed Central

Ali, Ather; Weiss, Theresa R; McKee, Douglas; Scherban, Alisa; Khan, Sumiya; Fields, Maxine R; Apollo, Damian; Mehal, Wajahat Z

2017-01-01

Background Patients with irritable bowel syndrome (IBS) are often placed on diets guided by food intolerance assays, although these have not been validated. We assessed the effects of individualised diets in patients with IBS guided by a leucocyte activation test. Methods This is a parallel-group, double-blind, randomised controlled trial of 58 adults with IBS seen at an academic health centre in Northeast USA. Peripheral venous blood was analysed using a leucocyte activation test; individual foods were reported to produce positive or negative results. Participants were randomised to a 4-week diet with either individualised guidance to eliminate foods with positive assay results and allow foods with negative assay results (intervention), or with individualised guidance, matched in rigour and complexity, to eliminate foods with negative assay results and allow foods with positive assay results (comparison). The primary outcome was between-group differences in the IBS Global Improvement Scale (GIS). Secondary outcomes included reductions in IBS Symptom Severity Scale (SSS) scores and increases in IBS Adequate Relief (AR) and Quality of Life (QOL) scores. An aptamer-based proteomic analysis was conducted in strong responders. Results The intervention group had significantly greater increases in mean GIS score after 4 weeks (0.86 vs comparison; 95% CI 0.05 to 1.67; p=0.04) and 8 weeks (1.22 vs comparison; 95% CI 0.22 to 2.22; p=0.02). The intervention group also had significantly greater reductions in mean SSS score at 4 weeks (–61.78 vs comparison; 95% CI –4.43 to –119.14; p=0.04) and 8 weeks (–66.42 vs comparison; 95% CI –5.75 to –127.09; p=0.03). There were no significant differences between intervention and comparison groups in mean AR or QOL scores. A reduction in neutrophil elastase concentration was associated with reduced symptoms. Conclusions Elimination diets guided by leucocyte activation tests reduced symptoms. These findings could lead to insights into the pathophysiology of IBS. Trial registration number NCT02186743. PMID:29018540

A Model-Based Product Evaluation Protocol for Comparison of Safety-Engineered Protection Mechanisms of Winged Blood Collection Needles.

PubMed

Haupt, C; Spaeth, J; Ahne, T; Goebel, U; Steinmann, D

2016-05-01

To evaluate differences in product characteristics and user preferences of safety-engineered protection mechanisms of winged blood collection needles. Randomized model-based simulation study. University medical center. A total of 33 third-year medical students. Venipuncture was performed using winged blood collection needles with 4 different safety mechanisms: (a) Venofix Safety, (b) BD Vacutainer Push Button, (c) Safety-Multifly, and (d) Surshield Surflo. Each needle type was used in 3 consecutive tries: there was an uninstructed first handling, then instructions were given according to the operating manual; subsequently, a first trial and second trial were conducted. Study end points included successful activation, activation time, single-handed activation, correct activation, possible risk of needlestick injury, possibility of deactivation, and preferred safety mechanism. The overall successful activation rate during the second trial was equal for all 4 devices (94%-100%). Median activation time was (a) 7 s, (b) 2 s, (c) 9 s, and (d) 7 s. Single-handed activation during the second trial was (a) 18%, (b) 82%, (c) 15%, and (d) 45%. Correct activation during the second trial was (a) 3%, (b) 64%, (c) 15%, and (d) 39%. Possible risk of needlestick injury during the second trial was highest with (d). Possibility of deactivation was (a) 0%, (b) 12%, (c) 9%, and (d) 18%. Individual preferences for each system were (a) 11, (b) 17, (c) 5, and (d) 0. The main reason for preference was the comprehensive safety mechanism. Significant differences exist between safety mechanisms of winged blood collection needles.

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

PubMed

Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C; Dworkin, Robert H; Katz, Nathaniel P; Kehlet, Henrik; Ballantyne, Jane C; Burke, Laurie B; Carragee, Eugene; Cowan, Penney; Croll, Scott; Dionne, Raymond A; Farrar, John T; Gilron, Ian; Gordon, Debra B; Iyengar, Smriti; Jay, Gary W; Kalso, Eija A; Kerns, Robert D; McDermott, Michael P; Raja, Srinivasa N; Rappaport, Bob A; Rauschkolb, Christine; Royal, Mike A; Segerdahl, Märta; Stauffer, Joseph W; Todd, Knox H; Vanhove, Geertrui F; Wallace, Mark S; West, Christine; White, Richard E; Wu, Christopher

2016-02-01

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.

Physical and Psychologic Effects of Aromatherapy Inhalation on Pregnant Women: A Randomized Controlled Trial

PubMed Central

2013-01-01

Abstract Objectives Stress reduction care is important for pregnant women to decrease obstetric complications and children's health problems after birth. The aim of this study is to clarify the physical and psychologic effects of inhalation aromatherapy on pregnant women. Essential oils with high linalool and linalyl acetate content that may be used during pregnancy were selected and among these, and the one preferred by the participant was used. Design This was a prospective, randomized, controlled trial. Settings/location This trial was performed at a gynecology outpatient department in a hospital in Kyoto, Japan. Participants The study included pregnant women in week 28 of a single pregnancy with a normal course. Interventions Participants were randomly assigned into an aromatherapy group and a control group. They were seated in the resting, seated position for 10 minutes. During the latter 5 minutes of each 10-minute session, aromatherapy inhalation was performed for the aromatherapy group. Outcome measures Before and after the intervention, the Profile of Mood States (POMS) was measured. During the trial, the heart-rate fluctuations were measured for the autonomic nervous system regulation. Results A total of 13 pregnant women participated in the trial. Seven (7) participants were assigned to the aromatherapy group and 6 participants to the control group. The results of the POMS were such that based on an intragroup comparison, significant differences were observed in the Tension-Anxiety score (p<0.05) and the Anger-Hostility score (p<0.05), and the respective improvements observed were due to aromatherapy. The results of the autonomic nervous system regulation were such that based on an intragroup comparison within the aromatherapy group, the parasympathetic nerve activity increased significantly (p<0.05). Conclusions Aromatherapy inhalation using essential oils containing linalyl acetate and linalool was found to be effective for the POMS and parasympathetic nerve activity, based on an intragroup comparison. However, based on a comparison between the groups, no substantial difference was observed; hence, further study is necessary in the future. PMID:23410527

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.

Trial-to-trial Adaptation: Parsing out the Roles of Cerebellum and BG in Predictive Motor Timing.

PubMed

Lungu, Ovidiu V; Bares, Martin; Liu, Tao; Gomez, Christopher M; Cechova, Ivica; Ashe, James

2016-07-01

We previously demonstrated that predictive motor timing (i.e., timing requiring visuomotor coordination in anticipation of a future event, such as catching or batting a ball) is impaired in patients with spinocerebellar ataxia (SCA) types 6 and 8 relative to healthy controls. Specifically, SCA patients had difficulties postponing their motor response while estimating the target kinematics. This behavioral difference relied on the activation of both cerebellum and striatum in healthy controls, but not in cerebellar patients, despite both groups activating certain parts of cerebellum during the task. However, the role of these two key structures in the dynamic adaptation of the motor timing to target kinematic properties remained unexplored. In the current paper, we analyzed these data with the aim of characterizing the trial-by-trial changes in brain activation. We found that in healthy controls alone, and in comparison with SCA patients, the activation in bilateral striatum was exclusively associated with past successes and that in the left putamen, with maintaining a successful performance across successive trials. In healthy controls, relative to SCA patients, a larger network was involved in maintaining a successful trial-by-trial strategy; this included cerebellum and fronto-parieto-temporo-occipital regions that are typically part of attentional network and action monitoring. Cerebellum was also part of a network of regions activated when healthy participants postponed their motor response from one trial to the next; SCA patients showed reduced activation relative to healthy controls in both cerebellum and striatum in the same contrast. These findings support the idea that cerebellum and striatum play complementary roles in the trial-by-trial adaptation in predictive motor timing. In addition to expanding our knowledge of brain structures involved in time processing, our results have implications for the understanding of BG disorders, such as Parkinson disease where feedback processing or reward learning is affected.

Perceived Activities and Participation Outcomes of a Yoga Intervention for Individuals with Parkinson's Disease: A Mixed Methods Study.

PubMed

Hawkins, Brent L; Van Puymbroeck, Marieke; Walter, Alysha; Sharp, Julia; Woshkolup, Kathleen; Urrea-Mendoza, Enrique; Revilla, Fredy; Schmid, Arlene A

2018-04-09

Parkinson's disease (PD) often leads to poor balance, increased falls, and fear of falling, all of which can reduce participation in life activities. Yoga, which usually includes physical exercise, can improve functioning and life participation; however, limited research has been conducted on the effects of yoga on life participation of individuals with PD. This study had two purposes: (1) to identify and understand the perceived activities and participation outcomes associated a therapeutic yoga intervention for individuals with PD; and (2) to compare the perceived activities and participation outcomes with the outcomes measured in the clinical trial. A single-blind, randomized, waitlist-controlled, phase II exploratory pilot study using an after-trial embedded mixed methods design (clinical trial Pro00041068) evaluated the effect of an 8-week Hatha Yoga intervention on individuals with PD. Directed content analysis was used to analyze focus group interviews with participants who completed the yoga intervention. Quantitative and qualitative data were merged and compared using a data comparison matrix. Qualitative analysis indicated many activities and participation outcomes. Comparison of qualitative and quantitative data indicated the yoga intervention led to improved balance, mobility, and functional gait, and fewer falls. These outcomes reached beyond the intervention and into participants' daily lives. Results support the use of Hatha Yoga as a community-based rehabilitation intervention for individuals with PD. Yoga, as part of an interdisciplinary approach to treatment, can improve many types of activities and participation outcomes (e.g., mobility, social relationships, self-care, handling stress, recreation).

Searching ClinicalTrials.gov did not change the conclusions of a systematic review.

PubMed

Wilson, Lisa M; Sharma, Ritu; Dy, Sydney M; Waldfogel, Julie M; Robinson, Karen A

2017-10-01

We assessed the effect of searching ClinicalTrials.gov on the conclusions of a systematic review. We conducted this case study concurrently with a systematic review. We searched ClinicalTrials.gov on March 9, 2016, to identify trial records eligible for inclusion in the review. Two independent reviewers screened ClinicalTrials.gov records. We compared conclusions and strength of evidence grade with and without ClinicalTrials.gov records for 31 comparisons and 2 outcomes. We identified 106 trials (53 in the peer-reviewed literature only, 23 in ClinicalTrials.gov only, and 30 in both sources). For one comparison, the addition of results identified through ClinicalTrials.gov reduced the pooled effect size. We found evidence of selective outcome reporting for two comparisons and suspected publication bias for another two comparisons. For all other comparisons, searching ClinicalTrials.gov did not change conclusions or the strength of evidence grading for the two outcomes. Our search of ClinicalTrials.gov bolstered suspicions of reporting biases but did not change either the conclusions or the strength of evidence grading. Further research is needed to determine the effect of searching ClinicalTrials.gov on the conclusions of systematic reviews in different topic areas and as the new rules for registration of trial results take effect. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

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

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

An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

PubMed

Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

2013-11-01

To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

A Comparison of Nurses’ Activities Under Two Models of Administration

DTIC Science & Technology

1985-08-01

Angela Sheehan, "Innovation in Cancer Nursing and the Role of the Nurse in Clinical Trials," Progress in Clinical and Biological Research 121 (1983): 87...by Diagnosis-Related Groups,* Annals of Internal Medicine 100 (April 1984): 576. 12Tony DeCrosta, " Megatrends in Nursing: 10 New Directions that are...in Clinical Trials." Progress in Clinical and Biological Research 121 (1983): 87-92. Beyers, Marjorie: Byre, Calvin: Levy, Paul: Mallin, Katherine

A Comparison of Randomised Controlled Trials in Health and Education

ERIC Educational Resources Information Center

Torgerson, Carole J.; Torgerson, David J.; Birks, Yvonne F.; Porthouse, Jill

2005-01-01

Health care and educational trials face similar methodological challenges. Methodological reviews of health care trials have shown that a significant proportion have methodological flaws. Whether or not educational trials have a similar proportion of poor-quality trials is unknown. The authors undertook a methodological comparison between health…

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study

PubMed Central

Fair, Damien A.; Choi, Alexander H.; Dosenbach, Yannic B.L.; Coalson, Rebecca S.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

2009-01-01

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we use an event-related design, which allowed us to isolate trial related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single-subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. PMID:19819000

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study.

PubMed

Fair, Damien A; Choi, Alexander H; Dosenbach, Yannic B L; Coalson, Rebecca S; Miezin, Francis M; Petersen, Steven E; Schlaggar, Bradley L

2010-08-01

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we used an event-related design, which allowed us to isolate trial-related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial-related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. 2009 Elsevier Inc. All rights reserved.

Outcome measurement in clinical trials for Ulcerative Colitis: towards standardisation

PubMed Central

Cooney, Rachel M; Warren, Bryan F; Altman, Douglas G; Abreu, Maria T; Travis, Simon PL

2007-01-01

Clinical trials on novel drug therapies require clear criteria for patient selection and agreed definitions of disease remission. This principle has been successfully applied in the field of rheumatology where agreed disease scoring systems have allowed multi-centre collaborations and facilitated audit across treatment centres. Unfortunately in ulcerative colitis this consensus is lacking. Thirteen scoring systems have been developed but none have been properly validated. Most trials choose different endpoints and activity indices, making comparison of results from different trials extremely difficult. International consensus on endoscopic, clinical and histological scoring systems is essential as these are the key components used to determine entry criteria and outcome measurements in clinical trials on ulcerative colitis. With multiple new therapies under development, there is a pressing need for consensus to be reached. PMID:17592647

Sequential parallel comparison design with binary and time-to-event outcomes.

PubMed

Silverman, Rachel Kloss; Ivanova, Anastasia; Fine, Jason

2018-04-30

Sequential parallel comparison design (SPCD) has been proposed to increase the likelihood of success of clinical trials especially trials with possibly high placebo effect. Sequential parallel comparison design is conducted with 2 stages. Participants are randomized between active therapy and placebo in stage 1. Then, stage 1 placebo nonresponders are rerandomized between active therapy and placebo. Data from the 2 stages are pooled to yield a single P value. We consider SPCD with binary and with time-to-event outcomes. For time-to-event outcomes, response is defined as a favorable event prior to the end of follow-up for a given stage of SPCD. We show that for these cases, the usual test statistics from stages 1 and 2 are asymptotically normal and uncorrelated under the null hypothesis, leading to a straightforward combined testing procedure. In addition, we show that the estimators of the treatment effects from the 2 stages are asymptotically normal and uncorrelated under the null and alternative hypothesis, yielding confidence interval procedures with correct coverage. Simulations and real data analysis demonstrate the utility of the binary and time-to-event SPCD. Copyright © 2018 John Wiley & Sons, Ltd.

Advice to stay active as a single treatment for low back pain and sciatica.

PubMed

Hilde, G; Hagen, K B; Jamtvedt, G; Winnem, M

2002-01-01

Low back pain is one of the most common conditions managed in primary care. Restricted activity, rest, and symptomatic analgesics are the most commonly prescribed treatment for low back pain and sciatica. To assess the effects of advice to stay active as single treatment for patients with low back pain. Computerised searches in MEDLINE, EMBASE, Sport, The Cochrane Controlled Trials Register, Musculoskeletal Group's Trials Register and Scisearch, and scanning of reference lists from relevant articles were undertaken. Relevant studies were also traced by contacting authors. Date of the most recent searches: December 1998. We included all randomised trials or quasi-randomised trials where the study population consisted of adult patients with low back pain or sciatica, in which one comparison group was advised to stay active. The main outcomes of interest were pain, functional status, recovery and return to work. Two reviewers independently selected trials for inclusion, assessed the validity of included trials and extracted data. Investigators were contacted to collect missing data or for clarification when needed. Four trials, with a total of 491 patients, were included. Advice to stay active was compared to advice to rest in bed in all trials. Two trials were assessed to have low risk of bias and two to have moderate to high risk of bias. The results were heterogeneous. Results from one high quality trial of patients with acute simple LBP found small differences in functional status [Weighted Mean Difference (on a 0-100 scale) 6.0 (95% CI: 1.5, 10.5)] and length of sick leave [WMD 3.4 days (95% CI: 1.6, 5.2)] in favour of staying active compared to advice to stay in bed for two days. The other high quality trial compared advice to stay active with advice to rest in bed for 14 days for patients with sciatic syndrome, and found no differences between the groups. One of the high quality trials also compared advice to stay active with exercises for patients with acute simple LBP, and found improvement in functional status and reduction in sick leave in favour of advice to stay active. The best available evidence suggests that advice to stay active alone has small beneficial effects for patients with acute simple low back pain, and little or no effect for patients with sciatica. There is no evidence that advice to stay active is harmful for either acute low back pain or sciatica. If there is no major difference between advice to stay active and advice to rest in bed, and there is potential harmful effects of prolonged bed rest, then it is reasonable to advise people with acute low back pain and sciatica to stay active. These conclusions are based on single trials.

WITHDRAWN: Advice to stay active as a single treatment for low-back pain and sciatica.

PubMed

Hilde, G; Hagen, K B; Jamtvedt, G; Winnem, M

2007-07-18

Low back pain is one of the most common conditions managed in primary care. Restricted activity, rest, and symptomatic analgesics are the most commonly prescribed treatment for low back pain and sciatica. To assess the effects of advice to stay active as single treatment for patients with low back pain. Computerised searches in MEDLINE, EMBASE, Sport, The Cochrane Controlled Trials Register, Musculoskeletal Group's Trials Register and Scisearch, and scanning of reference lists from relevant articles were undertaken. Relevant studies were also traced by contacting authors. Date of the most recent searches: December 1998. We included all randomised trials or quasi-randomised trials where the study population consisted of adult patients with low back pain or sciatica, in which one comparison group was advised to stay active. The main outcomes of interest were pain, functional status, recovery and return to work. Two reviewers independently selected trials for inclusion, assessed the validity of included trials and extracted data. Investigators were contacted to collect missing data or for clarification when needed. Four trials, with a total of 491 patients, were included. Advice to stay active was compared to advice to rest in bed in all trials. Two trials were assessed to have low risk of bias and two to have moderate to high risk of bias. The results were heterogeneous. Results from one high quality trial of patients with acute simple LBP found small differences in functional status [Weighted Mean Difference (on a 0-100 scale) 6.0 (95% CI: 1.5, 10.5)] and length of sick leave [WMD 3.4 days (95% CI: 1.6, 5.2)] in favour of staying active compared to advice to stay in bed for two days. The other high quality trial compared advice to stay active with advice to rest in bed for 14 days for patients with sciatic syndrome, and found no differences between the groups. One of the high quality trials also compared advice to stay active with exercises for patients with acute simple LBP, and found improvement in functional status and reduction in sick leave in favour of advice to stay active. The best available evidence suggests that advice to stay active alone has small beneficial effects for patients with acute simple low back pain, and little or no effect for patients with sciatica. There is no evidence that advice to stay active is harmful for either acute low back pain or sciatica. If there is no major difference between advice to stay active and advice to rest in bed, and there is potential harmful effects of prolonged bed rest, then it is reasonable to advise people with acute low back pain and sciatica to stay active. These conclusions are based on single trials.

Effectiveness and cost-effectiveness of erlotinib versus gefitinib in first-line treatment of epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients in Hong Kong.

PubMed

Lee, Vivian W Y; Schwander, Bjoern; Lee, Victor H F

2014-06-01

To compare the effectiveness and cost-effectiveness of erlotinib versus gefitinib as first-line treatment of epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients. DESIGN. Indirect treatment comparison and a cost-effectiveness assessment. Hong Kong. Those having epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer. Erlotinib versus gefitinib use was compared on the basis of four relevant Asian phase-III randomised controlled trials: one for erlotinib (OPTIMAL) and three for gefitinib (IPASS; NEJGSG; WJTOG). The cost-effectiveness assessment model simulates the transition between the health states: progression-free survival, progression, and death over a lifetime horizon. The World Health Organization criterion (incremental cost-effectiveness ratio <3 times of gross domestic product/capita:

Valx: A system for extracting and structuring numeric lab test comparison statements from text

PubMed Central

Hao, Tianyong; Liu, Hongfang; Weng, Chunhua

2017-01-01

Objectives To develop an automated method for extracting and structuring numeric lab test comparison statements from text and evaluate the method using clinical trial eligibility criteria text. Methods Leveraging semantic knowledge from the Unified Medical Language System (UMLS) and domain knowledge acquired from the Internet, Valx takes 7 steps to extract and normalize numeric lab test expressions: 1) text preprocessing, 2) numeric, unit, and comparison operator extraction, 3) variable identification using hybrid knowledge, 4) variable - numeric association, 5) context-based association filtering, 6) measurement unit normalization, and 7) heuristic rule-based comparison statements verification. Our reference standard was the consensus-based annotation among three raters for all comparison statements for two variables, i.e., HbA1c and glucose, identified from all of Type 1 and Type 2 diabetes trials in ClinicalTrials.gov. Results The precision, recall, and F-measure for structuring HbA1c comparison statements were 99.6%, 98.1%, 98.8% for Type 1 diabetes trials, and 98.8%, 96.9%, 97.8% for Type 2 Diabetes trials, respectively. The precision, recall, and F-measure for structuring glucose comparison statements were 97.3%, 94.8%, 96.1% for Type 1 diabetes trials, and 92.3%, 92.3%, 92.3% for Type 2 diabetes trials, respectively. Conclusions Valx is effective at extracting and structuring free-text lab test comparison statements in clinical trial summaries. Future studies are warranted to test its generalizability beyond eligibility criteria text. The open-source Valx enables its further evaluation and continued improvement among the collaborative scientific community. PMID:26940748

Valx: A System for Extracting and Structuring Numeric Lab Test Comparison Statements from Text.

PubMed

Hao, Tianyong; Liu, Hongfang; Weng, Chunhua

2016-05-17

To develop an automated method for extracting and structuring numeric lab test comparison statements from text and evaluate the method using clinical trial eligibility criteria text. Leveraging semantic knowledge from the Unified Medical Language System (UMLS) and domain knowledge acquired from the Internet, Valx takes seven steps to extract and normalize numeric lab test expressions: 1) text preprocessing, 2) numeric, unit, and comparison operator extraction, 3) variable identification using hybrid knowledge, 4) variable - numeric association, 5) context-based association filtering, 6) measurement unit normalization, and 7) heuristic rule-based comparison statements verification. Our reference standard was the consensus-based annotation among three raters for all comparison statements for two variables, i.e., HbA1c and glucose, identified from all of Type 1 and Type 2 diabetes trials in ClinicalTrials.gov. The precision, recall, and F-measure for structuring HbA1c comparison statements were 99.6%, 98.1%, 98.8% for Type 1 diabetes trials, and 98.8%, 96.9%, 97.8% for Type 2 diabetes trials, respectively. The precision, recall, and F-measure for structuring glucose comparison statements were 97.3%, 94.8%, 96.1% for Type 1 diabetes trials, and 92.3%, 92.3%, 92.3% for Type 2 diabetes trials, respectively. Valx is effective at extracting and structuring free-text lab test comparison statements in clinical trial summaries. Future studies are warranted to test its generalizability beyond eligibility criteria text. The open-source Valx enables its further evaluation and continued improvement among the collaborative scientific community.

Support or competition? How online social networks increase physical activity: A randomized controlled trial.

PubMed

Zhang, Jingwen; Brackbill, Devon; Yang, Sijia; Becker, Joshua; Herbert, Natalie; Centola, Damon

2016-12-01

To identify what features of online social networks can increase physical activity, we conducted a 4-arm randomized controlled trial in 2014 in Philadelphia, PA. Students (n = 790, mean age = 25.2) at an university were randomly assigned to one of four conditions composed of either supportive or competitive relationships and either with individual or team incentives for attending exercise classes. The social comparison condition placed participants into 6-person competitive networks with individual incentives. The social support condition placed participants into 6-person teams with team incentives. The combined condition with both supportive and competitive relationships placed participants into 6-person teams, where participants could compare their team's performance to 5 other teams' performances. The control condition only allowed participants to attend classes with individual incentives. Rewards were based on the total number of classes attended by an individual, or the average number of classes attended by the members of a team. The outcome was the number of classes that participants attended. Data were analyzed using multilevel models in 2014. The mean attendance numbers per week were 35.7, 38.5, 20.3, and 16.8 in the social comparison, the combined, the control, and the social support conditions. Attendance numbers were 90% higher in the social comparison and the combined conditions (mean = 1.9, SE = 0.2) in contrast to the two conditions without comparison (mean = 1.0, SE = 0.2) (p = 0.003). Social comparison was more effective for increasing physical activity than social support and its effects did not depend on individual or team incentives.

Lounging with robots--social spaces of residents in care: A comparison trial.

PubMed

Peri, Kathryn; Kerse, Ngaire; Broadbent, Elizabeth; Jayawardena, Chandimal; Kuo, Tony; Datta, Chandan; Stafford, Rebecca; MacDonald, Bruce

2016-03-01

To investigate whether robots could reduce resident sleeping and stimulate activity in the lounges of an older persons' care facility. Non-randomised controlled trial over a 12-week period. The intervention involved situating robots in low-level and high-dependency ward lounges and a comparison with similar lounges without robots. A time sampling observation method was utilised to observe resident behaviour, including sleep and activities over periods of time, to compare interactions in robot and no robot lounges. The use of robots was modest; overall 13% of residents in robot lounges used the robot. Utilisation was higher in the low-level care lounges; on average, 23% used the robot, whereas in high-level care lounges, the television being on was the strongest predictor of sleep. This study found that having robots in lounges was mostly a positive experience. The amount of time residents slept during the day was significantly less in low-level care lounges that had a robot. © 2015 AJA Inc.

A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure

PubMed Central

McMurray, John; Packer, Milton; Desai, Akshay; Gong, Jianjian; Greenlaw, Nicola; Lefkowitz, Martin; Rizkala, Adel; Shi, Victor; Rouleau, Jean; Solomon, Scott; Swedberg, Karl; Zile, Michael R.; Andersen, Karl; Arango, Juan Luis; Arnold, Malcolm; Be˘lohlávek, Jan; Böhm, Michael; Boytsov, Sergey; Burgess, Lesley; Cabrera, Walter; Chen, Chen-Huan; Erglis, Andrejs; Fu, Michael; Gomez, Efrain; Gonzalez, Angel; Hagege, Albert-Alain; Katova, Tzvetana; Kiatchoosakun, Songsak; Kim, Kee-Sik; Bayram, Edmundo; Martinez, Felipe; Merkely, Bela; Mendoza, Iván; Mosterd, Arend; Negrusz-Kawecka, Marta; Peuhkurinen, Keijo; Ramires, Felix; Refsgaard, Jens; Senni, Michele; Sibulo, Antonio S.; Silva-Cardoso, José; Squire, Iain; Starling, Randall C.; Vinereanu, Dragos; Teerlink, John R.; Wong, Raymond

2015-01-01

Aims Although active-controlled trials with renin–angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos. Methods and results We used the treatment-arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity-Alternative trial (CHARM-Alternative) as the reference trial for comparison of an ARB to placebo. The hazard ratio of LCZ696 vs. a putative placebo was estimated through the product of the hazard ratio of LCZ696 vs. enalapril (active-control) and that of the historical active-control (enalapril or candesartan) vs. placebo. For the primary composite outcome of cardiovascular death or heart failure hospitalization in PARADIGM-HF, the relative risk reduction with LCZ696 vs. a putative placebo from SOLVD-T was 43% (95%CI 34–50%; P < 0.0001) with similarly large effects on cardiovascular death (34%, 21–44%; P < 0.0001) and heart failure hospitalization (49%, 39–58%; P < 0.0001). For all-cause mortality, the reduction compared with a putative placebo was 28% (95%CI 15–39%; P < 0.0001). Putative placebo analyses based on CHARM-Alternative gave relative risk reductions of 39% (95%CI 27–48%; P < 0.0001) for the composite outcome of cardiovascular death or heart failure hospitalization, 32% (95%CI 16–45%; P < 0.0001) for cardiovascular death, 46% (33–56%; P < 0.0001) for heart failure hospitalization, and 26% (95%CI 11–39%; P < 0.0001) for all-cause mortality. Conclusion These indirect comparisons of LCZ696 with a putative placebo show that the strategy of combined angiotensin receptor blockade and neprilysin inhibition led to striking reductions in cardiovascular and all-cause mortality, as well as heart failure hospitalization. These benefits were obtained even though LCZ696 was added to comprehensive background beta-blocker and mineralocorticoid receptor antagonist therapy. PMID:25416329

Comparison of short-term energy intake and appetite responses to active and seated video gaming, in 8-11-year-old boys.

PubMed

Allsop, Susan; Green, Benjamin P; Dodd-Reynolds, Caroline J; Barry, Gillian; Rumbold, Penny L S

2016-03-28

The acute effects of active and seated video gaming on energy intake (EI), blood glucose, plasma glucagon-like peptide-1 (GLP-17-36) and subjective appetite (hunger, prospective food consumption and fullness) were examined in 8-11-year-old boys. In a randomised, crossover manner, twenty-two boys completed one 90-min active and one 90-min seated video gaming trial during which food and drinks were provided ad libitum. EI, plasma GLP-17-36, blood glucose and subjective appetite were measured during and following both trials. Time-averaged AUC blood glucose was increased (P=0·037); however, EI was lower during active video gaming (1·63 (sem 0·26) MJ) compared with seated video gaming (2·65 (sem 0·32) MJ) (P=0·000). In a post-gaming test meal 1 h later, there were no significant differences in EI between the active and seated gaming trials. Although estimated energy expenditure was significantly higher during active video gaming, there was still no compensation for the lower EI. At cessation of the trials, relative EI (REI) was significantly lower following active video gaming (2·06 (sem 0·30) MJ) v. seated video gaming (3·34 (sem 0·35) MJ) (P=0·000). No significant differences were detected in time-averaged AUC GLP-17-36 or subjective appetite. At cessation of the active video gaming trial, EI and REI were significantly less than for seated video gaming. In spite of this, the REI established for active video gaming was a considerable amount when considering the total daily estimated average requirement for 8-11-year-old boys in the UK (7·70 MJ).

Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis.

PubMed

Sundström, Johan; Arima, Hisatomi; Jackson, Rod; Turnbull, Fiona; Rahimi, Kazem; Chalmers, John; Woodward, Mark; Neal, Bruce

2015-02-03

Effects of blood pressure reduction in persons with grade 1 hypertension are unclear. To investigate whether pharmacologic blood pressure reduction prevents cardiovascular events and deaths in persons with grade 1 hypertension. Trials included in the BPLTTC (Blood Pressure Lowering Treatment Trialists' Collaboration) and trials identified from a previous review and electronic database searches. Patients without cardiovascular disease with blood pressures in the grade 1 hypertension range (140 to 159/90 to 99 mm Hg) who were randomly assigned to an active (antihypertensive drug or more intensive regimen) or control (placebo or less intensive regimen) blood pressure-lowering regimen. Individual-patient data from BPLTTC trials and aggregate data from other trials were extracted. Risk of bias was assessed for all trials. Individual-patient data involved 10 comparisons from trials where most patients had diabetes, and aggregate data involved 3 comparisons from trials of patients without diabetes. The average blood pressure reduction was about 3.6/2.4 mm Hg. Over 5 years, odds ratios were 0.86 (95% CI, 0.74 to 1.01) for total cardiovascular events, 0.72 (CI, 0.55 to 0.94) for strokes, 0.91 (CI, 0.74 to 1.12) for coronary events, 0.80 (CI, 0.57 to 1.12) for heart failure, 0.75 (CI, 0.57 to 0.98) for cardiovascular deaths, and 0.78 (CI, 0.67 to 0.92) for total deaths. Results were similar in secondary analyses. Withdrawal from treatment due to adverse effects was more common in the active groups. Blood pressure reductions and numbers of events were small. Blood pressure-lowering therapy is likely to prevent stroke and death in patients with uncomplicated grade 1 hypertension. Swedish Heart-Lung Foundation, Swedish Research Council, Australian Research Council, and National Health and Medical Research Council of Australia.

A Comparison Between Caucasians and African Americans in Willingness to Participate in Cancer Clinical Trials: The Roles of Knowledge, Distrust, Information Sources, and Religiosity.

PubMed

Meng, Jingbo; McLaughlin, Margaret; Pariera, Katrina; Murphy, Sheila

2016-06-01

This study aims to (a) examine the roles of knowledge, distrust in medical professionals, information sources, and 2 dimensions of religiosity (i.e., religious activity and religious belief) in influencing willingness to participate (WTP) in cancer clinical trials and to (b) compare the results for Caucasians and African Americans in order to inform future recruitment. An online survey was fielded via a Knowledge Networks panel with a nationally representative sample including 478 Caucasians and 173 African Americans. The results showed that distrust in medical professionals was a strong barrier to WTP for both ethnic groups, whereas factual knowledge about trial procedures was not associated with WTP for either ethnic group. Seeking trial information from doctors was positively associated with WTP for Caucasians; seeking trial information from hospitals was positively associated with WTP for African Americans. More interestingly, levels of religious activity negatively predicted WTP for Caucasians but positively predicted WTP for African Americans. Self-reported religious belief was not associated with WTP for either ethnic group. In sum, although distrust is a common barrier to WTP, the influence of preferred information sources and religious activity on WTP varies as a function of ethnicity.

Efficacy of individualised diets in patients with irritable bowel syndrome: a randomised controlled trial.

PubMed

Ali, Ather; Weiss, Theresa R; McKee, Douglas; Scherban, Alisa; Khan, Sumiya; Fields, Maxine R; Apollo, Damian; Mehal, Wajahat Z

2017-01-01

Patients with irritable bowel syndrome (IBS) are often placed on diets guided by food intolerance assays, although these have not been validated. We assessed the effects of individualised diets in patients with IBS guided by a leucocyte activation test. This is a parallel-group, double-blind, randomised controlled trial of 58 adults with IBS seen at an academic health centre in Northeast USA. Peripheral venous blood was analysed using a leucocyte activation test; individual foods were reported to produce positive or negative results. Participants were randomised to a 4-week diet with either individualised guidance to eliminate foods with positive assay results and allow foods with negative assay results (intervention), or with individualised guidance, matched in rigour and complexity, to eliminate foods with negative assay results and allow foods with positive assay results (comparison). The primary outcome was between-group differences in the IBS Global Improvement Scale (GIS). Secondary outcomes included reductions in IBS Symptom Severity Scale (SSS) scores and increases in IBS Adequate Relief (AR) and Quality of Life (QOL) scores. An aptamer-based proteomic analysis was conducted in strong responders. The intervention group had significantly greater increases in mean GIS score after 4 weeks (0.86 vs comparison; 95% CI 0.05 to 1.67; p=0.04) and 8 weeks (1.22 vs comparison; 95% CI 0.22 to 2.22; p=0.02). The intervention group also had significantly greater reductions in mean SSS score at 4 weeks (-61.78 vs comparison; 95% CI -4.43 to -119.14; p=0.04) and 8 weeks (-66.42 vs comparison; 95% CI -5.75 to -127.09; p=0.03). There were no significant differences between intervention and comparison groups in mean AR or QOL scores. A reduction in neutrophil elastase concentration was associated with reduced symptoms. Elimination diets guided by leucocyte activation tests reduced symptoms. These findings could lead to insights into the pathophysiology of IBS. NCT02186743.

Comparison of Infant and Adult P300 from Auditory Stimuli.

ERIC Educational Resources Information Center

McIsaac, Heather; Polich, John

1992-01-01

Recorded electroencephalographic activity of infants and adults who heard 1 unique tone in a series of 10 tones. The amplitude of event-related brain potentials in response to the unique tone was smaller, and its latency longer, for infants than for adults. Evoked potentials remained stable across trials. (BC)

Dissociable neural effects of stimulus valence and preceding context during the inhibition of responses to emotional faces.

PubMed

Schulz, Kurt P; Clerkin, Suzanne M; Halperin, Jeffrey M; Newcorn, Jeffrey H; Tang, Cheuk Y; Fan, Jin

2009-09-01

Socially appropriate behavior requires the concurrent inhibition of actions that are inappropriate in the context. This self-regulatory function requires an interaction of inhibitory and emotional processes that recruits brain regions beyond those engaged by either processes alone. In this study, we isolated brain activity associated with response inhibition and emotional processing in 24 healthy adults using event-related functional magnetic resonance imaging (fMRI) and a go/no-go task that independently manipulated the context preceding no-go trials (ie, number of go trials) and the valence (ie, happy, sad, and neutral) of the face stimuli used as trial cues. Parallel quadratic trends were seen in correct inhibitions on no-go trials preceded by increasing numbers of go trials and associated activation for correct no-go trials in inferior frontal gyrus pars opercularis, pars triangularis, and pars orbitalis, temporoparietal junction, superior parietal lobule, and temporal sensory association cortices. Conversely, the comparison of happy versus neutral faces and sad versus neutral faces revealed valence-dependent activation in the amygdala, anterior insula cortex, and posterior midcingulate cortex. Further, an interaction between inhibition and emotion was seen in valence-dependent variations in the quadratic trend in no-go activation in the right inferior frontal gyrus and left posterior insula cortex. These results suggest that the inhibition of response to emotional cues involves the interaction of partly dissociable limbic and frontoparietal networks that encode emotional cues and use these cues to exert inhibitory control over the motor, attention, and sensory functions needed to perform the task, respectively. 2008 Wiley-Liss, Inc.

Bioassays and field immersion tests: a comparison of the antifouling activity of copper-free poly(methacrylic)-based coatings containing tertiary amines and ammonium salt groups.

PubMed

Bressy, C; Hellio, C; Marechal, J P; Tanguy, B; Margaillan, A

2010-10-01

This paper focuses on the activity spectrum of three dimethylalkyl tertiary amines as potential active molecules and the corresponding ammonium salt-based antifouling (AF) paints. Bioassays (using marine bacteria, microalgae and barnacles) and field tests were combined to assess the AF activity of coatings. Bioassay results demonstrated that the ammonium salt-based paints did not inhibit the growth of microorganisms (except the dimethyldodecylammonium-based coatings) and that the tertiary amines were potent towards bacteria, diatoms, and barnacle larvae at non-toxic concentrations (therapeutic ratio, LC50/EC50, <1). The results from field tests indicated that the ammonium salt-based coatings inhibited the settlement of macrofouling and the dimethylhexadecylammonium-based coatings provided protection against slime in comparison with PVC blank panels. Thus, results from laboratory assays did not fully concur with the AF activity of the paints in the field trial.

Optimistic Biases in Observational Learning of Value

ERIC Educational Resources Information Center

Nicolle, A.; Symmonds, M.; Dolan, R. J.

2011-01-01

Action-outcome contingencies can be learnt either by active trial-and-error, or vicariously, by observing the outcomes of actions performed by others. The extant literature is ambiguous as to which of these modes of learning is more effective, as controlled comparisons of operant and observational learning are rare. Here, we contrasted human…

Meta-Analysis of Dropout in Treatments for Posttraumatic Stress Disorder

ERIC Educational Resources Information Center

Imel, Zac E.; Laska, Kevin; Jakupcak, Matthew; Simpson, Tracy L.

2013-01-01

Objective: Many patients drop out of treatments for posttraumatic stress disorder (PTSD); some clinicians believe that trauma-focused treatments increase dropout. Method: We conducted a meta-analysis of dropout among active treatments in clinical trials for PTSD (42 studies; 17 direct comparisons). Results: The average dropout rate was 18%, but it…

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

Design and analysis of three-arm trials with negative binomially distributed endpoints.

PubMed

Mütze, Tobias; Munk, Axel; Friede, Tim

2016-02-20

A three-arm clinical trial design with an experimental treatment, an active control, and a placebo control, commonly referred to as the gold standard design, enables testing of non-inferiority or superiority of the experimental treatment compared with the active control. In this paper, we propose methods for designing and analyzing three-arm trials with negative binomially distributed endpoints. In particular, we develop a Wald-type test with a restricted maximum-likelihood variance estimator for testing non-inferiority or superiority. For this test, sample size and power formulas as well as optimal sample size allocations will be derived. The performance of the proposed test will be assessed in an extensive simulation study with regard to type I error rate, power, sample size, and sample size allocation. For the purpose of comparison, Wald-type statistics with a sample variance estimator and an unrestricted maximum-likelihood estimator are included in the simulation study. We found that the proposed Wald-type test with a restricted variance estimator performed well across the considered scenarios and is therefore recommended for application in clinical trials. The methods proposed are motivated and illustrated by a recent clinical trial in multiple sclerosis. The R package ThreeArmedTrials, which implements the methods discussed in this paper, is available on CRAN. Copyright © 2015 John Wiley & Sons, Ltd.

Metrics Survey of Industry-Sponsored Clinical Trials in Canada and Comparator Jurisdictions between 2005 and 2010

PubMed Central

Leclerc, Jean-Marie; Laberge, Normand; Marion, Jean

2012-01-01

Industry-sponsored clinical trials play a key role in the development of therapies. This survey suggests that between 2005 and 2010, research-based pharmaceutical firms worldwide initiated fewer trials and recruited fewer subjects annually. In contrast, at the country level, the clinical trial activity of such firms increased in emerging countries and in Japan. Canada's trend in the number of new trials followed that of the global industry, but the trend in new sites and newly recruited subjects fell below the global rate. Informal comparisons point to potential issues for Canada in such areas as site capacity, cost per subject and time to first subject-in. When compared to certain Western European countries and the United States, Canada remained well positioned on a number of metrics. Nonetheless, Canada faces mounting challenges from both traditional locations and emerging countries and may require coordinated efforts to remain a place of choice to conduct trials. PMID:23968618

Biologic agents in rheumatology: unmet issues after 200 trials and $200 billion sales.

PubMed

Ioannidis, John P A; Karassa, Fotini B; Druyts, Eric; Thorlund, Kristian; Mills, Edward J

2013-11-01

Anti-TNF agents and other biologic therapies are widely prescribed for a variety of indications, with total sales that exceed $200 billion to date. In rheumatic diseases, biologic agents have now been studied in more than 200 randomized clinical trials and over 100 subsequent meta-analyses; however, the information obtained does not always meet the needs of patients and clinicians. In this Review, we discuss the current issues concerning the evidence derived from such studies: potential biases favouring positive results; a paucity of head-to-head comparisons between biologically active agents; overwhelming involvement of manufacturer sponsors in trials and in the synthesis of the evidence; the preference for trials with limited follow-up; and the potential for spurious findings on adverse events, leading to endless debates about malignancy risk. We debate the responsibilities of regulatory authorities, the pharmaceutical industry and academia in attempting to solve these shortcomings and challenges. We propose that improvements in the evidence regarding biologic treatments that are continually being added to the therapeutic armamentarium for rheumatic diseases might require revisiting the design and conduct of studies. For example, trials with long-term follow-up that are independent of the pharmaceutical industry, head-to-head comparisons of therapeutic agents and the use of rigorous clinical outcomes should be considered, and public availability of raw data endorsed.

Fe en Accion/Faith in Action: Design and implementation of a church-based randomized trial to promote physical activity and cancer screening among churchgoing Latinas

PubMed Central

Arredondo, Elva M.; Haughton, Jessica; Ayala, Guadalupe X.; Slymen, Donald J.; Sallis, James F.; Burke, Kari; Holub, Christina; Chanson, Dayana; Perez, Lilian G.; Valdivia, Rodrigo; Ryan, Sherry; Elder, John

2015-01-01

Objectives To describe both conditions of a two-group randomized trial, one that promotes physical activity and one that promotes cancer screening, among churchgoing Latinas. The trial involves promotoras (community health workers) targeting multiple levels of the Ecological Model. This trial builds on formative and pilot research findings. Design Sixteen churches were randomly assigned to either the physical activity intervention or cancer screening comparison condition (approximately 27 women per church). In both conditions, promotoras from each church intervened at the individual- (e.g., beliefs), interpersonal- (e.g., social support), and environmental- (e.g., park features and access to health care) levels to affect change on target behaviors. Measurements The study’s primary outcome is min/wk of moderate-to-vigorous physical activity (MVPA) at baseline and 12 and 24 months following implementation of intervention activities. We enrolled 436 Latinas (aged 18–65 years) who engaged in less than 250 min/wk of MVPA at baseline as assessed by accelerometer, attended church at least four times per month, lived near their church, and did not have a health condition that could prevent them from participating in physical activity. Participants were asked to complete measures assessing physical activity and cancer screening as well as their correlates at 12- and 24-months. Summary Findings from the current study will address gaps in research by showing the long term effectiveness of multi-level faith-based interventions promoting physical activity and cancer screening among Latino communities. PMID:26358535

Follow-up of blood-pressure lowering and glucose control in type 2 diabetes.

PubMed

Zoungas, Sophia; Chalmers, John; Neal, Bruce; Billot, Laurent; Li, Qiang; Hirakawa, Yoichiro; Arima, Hisatomi; Monaghan, Helen; Joshi, Rohina; Colagiuri, Stephen; Cooper, Mark E; Glasziou, Paul; Grobbee, Diederick; Hamet, Pavel; Harrap, Stephen; Heller, Simon; Lisheng, Liu; Mancia, Giuseppe; Marre, Michel; Matthews, David R; Mogensen, Carl E; Perkovic, Vlado; Poulter, Neil; Rodgers, Anthony; Williams, Bryan; MacMahon, Stephen; Patel, Anushka; Woodward, Mark

2014-10-09

In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up. We invited surviving participants, who had previously been assigned to perindopril-indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events. The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure-lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively. The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events. (Funded by the National Health and Medical Research Council of Australia and others; ADVANCE-ON ClinicalTrials.gov number, NCT00949286.).

Family, Community and Clinic Collaboration to Treat Overweight and Obese Children: Stanford GOALS -- a Randomized Controlled Trial of a Three-Year, Multi-Component, Multi-Level, Multi-Setting Intervention

PubMed Central

Robinson, Thomas N.; Matheson, Donna; Desai, Manisha; Wilson, Darrell M.; Weintraub, Dana L.; Haskell, William L.; McClain, Arianna; McClure, Samuel; Banda, Jorge; Sanders, Lee M.; Haydel, K. Farish; Killen, Joel D.

2013-01-01

Objective To test the effects of a three-year, community-based, multi-component, multi-level, multi-setting (MMM) approach for treating overweight and obese children. Design Two-arm, parallel group, randomized controlled trial with measures at baseline, 12, 24, and 36 months after randomization. Participants Seven through eleven year old, overweight and obese children (BMI ≥ 85th percentile) and their parents/caregivers recruited from community locations in low-income, primarily Latino neighborhoods in Northern California. Interventions Families are randomized to the MMM intervention versus a community health education active-placebo comparison intervention. Interventions last for three years for each participant. The MMM intervention includes a community-based after school team sports program designed specifically for overweight and obese children, a home-based family intervention to reduce screen time, alter the home food/eating environment, and promote self-regulatory skills for eating and activity behavior change, and a primary care behavioral counseling intervention linked to the community and home interventions. The active-placebo comparison intervention includes semi-annual health education home visits, monthly health education newsletters for children and for parents/guardians, and a series of community-based health education events for families. Main Outcome Measure Body mass index trajectory over the three-year study. Secondary outcome measures include waist circumference, triceps skinfold thickness, accelerometer-measured physical activity, 24-hour dietary recalls, screen time and other sedentary behaviors, blood pressure, fasting lipids, glucose, insulin, hemoglobin A1c, C-reactive protein, alanine aminotransferase, and psychosocial measures. Conclusions The Stanford GOALS trial is testing the efficacy of a novel community-based multi-component, multi-level, multi-setting treatment for childhood overweight and obesity in low-income, Latino families. PMID:24028942

Family, community and clinic collaboration to treat overweight and obese children: Stanford GOALS-A randomized controlled trial of a three-year, multi-component, multi-level, multi-setting intervention.

PubMed

Robinson, Thomas N; Matheson, Donna; Desai, Manisha; Wilson, Darrell M; Weintraub, Dana L; Haskell, William L; McClain, Arianna; McClure, Samuel; Banda, Jorge A; Sanders, Lee M; Haydel, K Farish; Killen, Joel D

2013-11-01

To test the effects of a three-year, community-based, multi-component, multi-level, multi-setting (MMM) approach for treating overweight and obese children. Two-arm, parallel group, randomized controlled trial with measures at baseline, 12, 24, and 36 months after randomization. Seven through eleven year old, overweight and obese children (BMI ≥ 85th percentile) and their parents/caregivers recruited from community locations in low-income, primarily Latino neighborhoods in Northern California. Families are randomized to the MMM intervention versus a community health education active-placebo comparison intervention. Interventions last for three years for each participant. The MMM intervention includes a community-based after school team sports program designed specifically for overweight and obese children, a home-based family intervention to reduce screen time, alter the home food/eating environment, and promote self-regulatory skills for eating and activity behavior change, and a primary care behavioral counseling intervention linked to the community and home interventions. The active-placebo comparison intervention includes semi-annual health education home visits, monthly health education newsletters for children and for parents/guardians, and a series of community-based health education events for families. Body mass index trajectory over the three-year study. Secondary outcome measures include waist circumference, triceps skinfold thickness, accelerometer-measured physical activity, 24-hour dietary recalls, screen time and other sedentary behaviors, blood pressure, fasting lipids, glucose, insulin, hemoglobin A1c, C-reactive protein, alanine aminotransferase, and psychosocial measures. The Stanford GOALS trial is testing the efficacy of a novel community-based multi-component, multi-level, multi-setting treatment for childhood overweight and obesity in low-income, Latino families. © 2013 Elsevier Inc. All rights reserved.

The Mental Activity and eXercise (MAX) trial: a randomized controlled trial to enhance cognitive function in older adults.

PubMed

Barnes, Deborah E; Santos-Modesitt, Wendy; Poelke, Gina; Kramer, Arthur F; Castro, Cynthia; Middleton, Laura E; Yaffe, Kristine

2013-05-13

The prevalence of cognitive impairment and dementia are projected to rise dramatically during the next 40 years, and strategies for maintaining cognitive function with age are critically needed. Physical or mental activity alone result in relatively small, domain-specific improvements in cognitive function in older adults; combined interventions may have more global effects. To examine the combined effects of physical plus mental activity on cognitive function in older adults. Randomized controlled trial with a factorial design. San Francisco, California. A total of 126 inactive, community-residing older adults with cognitive complaints. All participants engaged in home-based mental activity (1 h/d, 3 d/wk) plus class-based physical activity (1 h/d, 3 d/wk) for 12 weeks and were randomized to either mental activity intervention (MA-I; intensive computer) or mental activity control (MA-C; educational DVDs) plus exercise intervention (EX-I; aerobic) or exercise control (EX-C; stretching and toning); a 2 × 2 factorial design was used so that there were 4 groups: MA-I/EX-I, MA-I/EX-C, MA-C/EX-1, and MA-C/EX-C. Global cognitive change based on a comprehensive neuropsychological test battery. Participants had a mean age of 73.4 years; 62.7% were women, and 34.9% were Hispanic or nonwhite. There were no significant differences between the groups at baseline. Global cognitive scores improved significantly over time (mean, 0.16 SD; P < .001) but did not differ between groups in the comparison between MA-I and MA-C (ignoring exercise, P = .17), the comparison between EX-I and EX-C (ignoring mental activity, P = .74), or across all 4 randomization groups (P = .26). In inactive older adults with cognitive complaints, 12 weeks of physical plus mental activity was associated with significant improvements in global cognitive function with no evidence of difference between intervention and active control groups. These findings may reflect practice effects or may suggest that the amount of activity is more important than the type in this subject population. clinicaltrials.gov Identifier: NCT00522899.

Acquisition of an instrumental activity of daily living in patients with Korsakoff's syndrome: a comparison of trial and error and errorless learning.

PubMed

Oudman, Erik; Nijboer, Tanja C W; Postma, Albert; Wijnia, Jan W; Kerklaan, Sandra; Lindsen, Karen; Van der Stigchel, Stefan

2013-01-01

Patients with Korsakoff's syndrome show devastating amnesia and executive deficits. Consequently, the ability to perform instrumental activities such as making coffee is frequently diminished. It is currently unknown whether patients with Korsakoff's syndrome are able to (re)learn instrumental activities. A good candidate for an effective teaching technique in Korsakoff's syndrome is errorless learning as it is based on intact implicit memory functioning. Therefore, the aim of the current study was two-fold: to investigate whether patients with Korsakoff's syndrome are able to (re)learn instrumental activities, and to compare the effectiveness of errorless learning with trial and error learning in the acquisition and maintenance of an instrumental activity, namely using a washing machine to do the laundry. Whereas initial learning performance in the errorless learning condition was superior, both intervention techniques resulted in similar improvement over eight learning sessions. Moreover, performance in a different spatial layout showed a comparable improvement. Notably, in follow-up sessions starting after four weeks without practice, performance was still elevated in the errorless learning condition, but not in the trial and error condition. The current study demonstrates that (re)learning and maintenance of an instrumental activity is possible in patients with Korsakoff's syndrome.

The influence of a consumer-wearable activity tracker on sedentary time and prolonged sedentary bouts: secondary analysis of a randomized controlled trial.

PubMed

Sloan, Robert A; Kim, Youngdeok; Sahasranaman, Aarti; Müller-Riemenschneider, Falk; Biddle, Stuart J H; Finkelstein, Eric A

2018-03-22

A recent meta-analysis surmised pedometers were a useful panacea to independently reduce sedentary time (ST). To further test and expand on this deduction, we analyzed the ability of a consumer-wearable activity tracker to reduce ST and prolonged sedentary bouts (PSB). We originally conducted a 12-month randomized control trial where 800 employees from 13 organizations were assigned to control, activity tracker, or one of two activity tracker plus incentive groups designed to increase step count. The primary outcome was accelerometer measured moderate-to-vigorous physical activity. We conducted a secondary analysis on accelerometer measured daily ST and PSB bouts. A general linear mixed model was used to examine changes in ST and prolonged sedentary bouts, followed by between-group pairwise comparisons. Regression analyses were conducted to examine the association of changes in step counts with ST and PSB. The changes in ST and PSB were not statistically significant and not different between the groups (P < 0.05). Increases in step counts were concomitantly associated with decreases in ST and PSB, regardless of intervention (P < 0.05). Caution should be taken when considering consumer-wearable activity trackers as a means to reduce sedentary behavior. Trial registration NCT01855776 Registered: August 8, 2012.

The efficacy of cognitive-behavioral therapy for eating disorders: A systematic review and meta-analysis.

PubMed

Linardon, Jake; Wade, Tracey D; de la Piedad Garcia, Xochitl; Brennan, Leah

2017-11-01

This meta-analysis examined the efficacy of cognitive-behavioral therapy (CBT) for eating disorders. Randomized controlled trials of CBT were searched. Seventy-nine trials were included. Therapist-led CBT was more efficacious than inactive (wait-lists) and active (any psychotherapy) comparisons in individuals with bulimia nervosa and binge eating disorder. Therapist-led CBT was most efficacious when manualized CBT-BN or its enhanced version was delivered. No significant differences were observed between therapist-led CBT for bulimia nervosa and binge eating disorder and antidepressants at posttreatment. CBT was also directly compared to other specific psychological interventions, and therapist-led CBT resulted in greater reductions in behavioral and cognitive symptoms than interpersonal psychotherapy at posttreatment. At follow-up, CBT outperformed interpersonal psychotherapy only on cognitive symptoms. CBT for binge eating disorder also resulted in greater reductions in behavioral symptoms than behavioral weight loss interventions. There was no evidence that CBT was more efficacious than behavior therapy or nonspecific supportive therapies. CBT is efficacious for eating disorders. Although CBT was equally efficacious to certain psychological treatments, the fact that CBT outperformed all active psychological comparisons and interpersonal psychotherapy specifically, offers some support for the specificity of psychological treatments for eating disorders. Conclusions from this study are hampered by the fact that many trials were of poor quality. Higher quality RCTs are essential. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effectiveness of a Group Support Lifestyle Modification (GSLiM) Programme among Obese Adults in Workplace: A Randomised Controlled Trial

PubMed Central

Azmi Mohamed, Mohd Nahar; Mukhtar, Firdaus

2016-01-01

Background There was an increasing trend in the prevalence of obesity and its comorbidities over the past decades in Malaysia. Effective intervention for obesity remains limited. This study aimed to compare the effectiveness of a group based lifestyle modification programme amongst obese individuals with an existing dietary counseling programme. Methods We recruited one hundred and ninety four overweight and obese (BMI>27.5 kg/m2) employees from a local university. They were randomly allocated to either Group Support Lifestyle Modification (GSLiM) (intervention)(n = 97) or dietary counseling (comparison)(n = 97). The GSLIM activities included self monitoring, cognitive-behaviour sessions, exercise as well as dietary change advocacy, which were conducted through seminars and group sessions over 24 weeks. The comparison group was given dietary counselling once in 12 weeks. Both groups were followed up for additional 12 weeks to check for intervention effect sustenance. Anthropometric and biochemical parameters were measured at baseline, 12, 24 and 36 weeks; while dietary intake, physical activities, psychological measures and quality of life measured at baseline, 24 and 36 weeks. Data analysis was conducted using ANOVA repeated measures with intention to treat principle. Results The participants were predominantly women with mean (standard deviation) age of 40.5 (9.3) years. A total of 19.6% of the participants in GSLiM achieved 6% weight loss compared to 4.1% in the comparison group (Risk Ratio 4.75; 95% CI: 1.68, 13.45). At 24 weeks, the retention rate was 83.5% for GSLiM and 82.5% for comparison group. GSLiM participants also achieved significant improvement in total weight self-efficacy score, negative emotions and physical discomfort subscales, MDPSS friend subscale and all domains in quality of life. Participants in the comparison group experienced reduction in negative self-thoughts. Conclusion The GSLiM programme proved to be more effective in achieving targeted weight loss, improving weight self-efficacy, friend social support, and quality of life compared to dietary counseling. Trial Registration Iranian Registry of Clinical Trials IRCT201104056127N1 PMID:27537687

Multigroup Propensity Score Approach to Evaluating an Effectiveness Trial of the New Beginnings Program.

PubMed

Tein, Jenn-Yun; Mazza, Gina L; Gunn, Heather J; Kim, Hanjoe; Stuart, Elizabeth A; Sandler, Irwin N; Wolchik, Sharlene A

2018-06-01

We used a multigroup propensity score approach to evaluate a randomized effectiveness trial of the New Beginnings Program (NBP), an intervention targeting divorced or separated families. Two features of effectiveness trials, high nonattendance rates and inclusion of an active control, make program effects harder to detect. To estimate program effects based on actual intervention participation, we created a synthetic inactive control comprised of nonattenders and assessed the impact of attending the NBP or active control relative to no intervention (inactive control). We estimated propensity scores using generalized boosted models and applied inverse probability of treatment weighting for the comparisons. Relative to the inactive control, NBP strengthened parenting quality as well as reduced child exposure to interparental conflict, parent psychological distress, and child internalizing problems. Some effects were moderated by parent gender, parent ethnicity, or child age. On the other hand, the effects of active versus inactive control were minimal for parenting and in the unexpected direction for child internalizing problems. Findings from the propensity score approach complement and enhance the interpretation of findings from the intention-to-treat approach.

A cluster randomised controlled trial of a staff-training intervention in residential units for people with long-term mental illness in Portugal: the PromQual trial.

PubMed

Cardoso, Graça; Papoila, Ana; Tomé, Gina; Killaspy, Helen; King, Michael; Caldas-de-Almeida, José Miguel

2017-11-01

This study aimed to assess the efficacy of a staff-training intervention to improve service users' engagement in activities and quality of care, by means of a cluster randomised controlled trial. All residential units with at least 12-h a day staff support (n = 23) were invited to participate. Quality of care was assessed with the Quality Indicator for Rehabilitative Care (QuIRC) filled online by the unit's manager. Half the units (n = 12) were randomly assigned to continue providing treatment as usual, and half (n = 11) received a staff-training intervention that focused on skills for engaging service users in activities, with trainers working alongside staff to embed this learning in the service. The primary outcome was service users' level of activity (measured with the Time Use Diary), reassessed at 4 and 8 months. Secondary outcomes were the quality of care provided (QuIRC), and service users' quality of life (Manchester Short Assessment of Quality of Life) reassessed at 8 months. Generalized linear mixed effect models were used to assess the difference in outcomes between units in the two trial arms. The trial was registered with Current Controlled Trials (Ref NCT02366117). Knowledge acquired by the staff during the initial workshops increased significantly (p ≤ 0.01). However, the intervention and comparison units did not differ significantly in primary and secondary outcomes at either follow-up. The intervention increased the level of knowledge of staff without leading to an improvement in service users' engagement in activities, quality of life, or quality of care in the units.

Weight management for overweight and obese men delivered through professional football clubs: a pilot randomized trial

PubMed Central

2013-01-01

Background The prevalence of male obesity is increasing, but men are less likely than women to attend existing weight management programmes. We have taken a novel approach to reducing perceived barriers to weight loss for men by using professional football (soccer) clubs to encourage participation in a weight management group programme, gender-sensitised in content and style of delivery. Football Fans in Training (FFIT) provides 12 weeks of weight loss, physical activity and healthy eating advice at top professional football clubs in Scotland. This pilot randomized trial explored the feasibility of using these clubs as a setting for a randomized controlled trial of 12 month weight loss following men’s participation in FFIT. Methods A two-arm pilot trial at two Scottish Premier League football clubs (one large, one smaller), with 103 men (aged 35–65, body mass index (BMI) ≥27 kg/m2) individually randomized to the intervention (n=51, received the pilot programme (p-FFIT) immediately) and waitlist comparison (n=52, received p-FFIT after four months) groups. Feasibility of recruitment, randomization, data collection and retention were assessed. Objective physical measurements (weight, waist circumference, blood pressure, body composition) and questionnaires (self-reported physical activity, diet, alcohol consumption, psychological outcomes) were obtained from both groups by fieldworkers trained to standard protocols at baseline and 12 weeks, and from the intervention group at 6 and 12 months. Qualitative methods elicited men’s experiences of participation in the pilot trial. Results Following a short recruitment period, the recruitment target was achieved at the large, but not smaller, club. Participants’ mean age was 47.1±8.4 years; mean BMI 34.5±5.0 kg/m2. Retention through the trial was good (>80% at 12 weeks and 6 months; >75% at 12 months), and 76% attended at least 80% of available programme delivery sessions. At 12 weeks, the intervention group lost significantly more weight than the comparison group (4.6% c.f. -0.6%, p<.001) and many maintained this to 12 months (intervention group baseline-12 month weight loss: 3.5%, p<.001). There were also improvements in self-reported physical activity and diet, many sustained long term. Conclusions The results demonstrated the feasibility of trial procedures and the potential of FFIT to engage men in sustained weight loss and positive lifestyle change. They supported the conduct of a fully-powered randomized controlled trial. PMID:24171842

Interventions for paracetamol (acetaminophen) overdose.

PubMed

Chiew, Angela L; Gluud, Christian; Brok, Jesper; Buckley, Nick A

2018-02-23

Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various interventions to treat paracetamol poisoning, depending on the clinical status of the person. These interventions include inhibiting the absorption of paracetamol from the gastrointestinal tract (decontamination), removal of paracetamol from the vascular system, and antidotes to prevent the formation of, or to detoxify, metabolites. To assess the benefits and harms of interventions for paracetamol overdosage irrespective of the cause of the overdose. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2017), CENTRAL (2016, Issue 11), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), and Science Citation Index Expanded (1900 to January 2017). We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov database (US National Institute of Health) for any ongoing or completed trials (January 2017). We examined the reference lists of relevant papers identified by the search and other published reviews. Randomised clinical trials assessing benefits and harms of interventions in people who have ingested a paracetamol overdose. The interventions could have been gastric lavage, ipecacuanha, or activated charcoal, or various extracorporeal treatments, or antidotes. The interventions could have been compared with placebo, no intervention, or to each other in differing regimens. Two review authors independently extracted data from the included trials. We used fixed-effect and random-effects Peto odds ratios (OR) with 95% confidence intervals (CI) for analysis of the review outcomes. We used the Cochrane 'Risk of bias' tool to assess the risks of bias (i.e. systematic errors leading to overestimation of benefits and underestimation of harms). We used Trial Sequential Analysis to control risks of random errors (i.e. play of chance) and GRADE to assess the quality of the evidence and constructed 'Summary of findings' tables using GRADE software. We identified 11 randomised clinical trials (of which one acetylcysteine trial was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol, or acetylcysteine. There were no randomised clinical trials of agents that inhibit cytochrome P-450 to decrease the activation of the toxic metabolite N-acetyl-p-benzoquinone imine.Of the 11 trials, only two had two common outcomes, and hence, we could only meta-analyse two comparisons. Each of the remaining comparisons included outcome data from one trial only and hence their results are presented as described in the trials. All trial analyses lack power to access efficacy. Furthermore, all the trials were at high risk of bias. Accordingly, the quality of evidence was low or very low for all comparisons. Interventions that prevent absorption, such as gastric lavage, ipecacuanha, or activated charcoal were compared with placebo or no intervention and with each other in one four-armed randomised clinical trial involving 60 participants with an uncertain randomisation procedure and hence very low quality. The trial presented results on lowering plasma paracetamol levels. Activated charcoal seemed to reduce the absorption of paracetamol, but the clinical benefits were unclear. Activated charcoal seemed to have the best risk:benefit ratio among gastric lavage, ipecacuanha, or supportive treatment if given within four hours of ingestion. There seemed to be no difference between gastric lavage and ipecacuanha, but gastric lavage and ipecacuanha seemed more effective than no treatment (very low quality of evidence). Extracorporeal interventions included charcoal haemoperfusion compared with conventional treatment (supportive care including gastric lavage, intravenous fluids, and fresh frozen plasma) in one trial with 16 participants. The mean cumulative amount of paracetamol removed was 1.4 g. One participant from the haemoperfusion group who had ingested 135 g of paracetamol, died. There were no deaths in the conventional treatment group. Accordingly, we found no benefit of charcoal haemoperfusion (very low quality of evidence). Acetylcysteine appeared superior to placebo and had fewer adverse effects when compared with dimercaprol or cysteamine. Acetylcysteine superiority to methionine was unproven. One small trial (low quality evidence) found that acetylcysteine may reduce mortality in people with fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The most recent randomised clinical trials studied different acetylcysteine regimens, with the primary outcome being adverse events. It was unclear which acetylcysteine treatment protocol offered the best efficacy, as most trials were underpowered to look at this outcome. One trial showed that a modified 12-hour acetylcysteine regimen with a two-hour acetylcysteine 100 mg/kg bodyweight loading dose was associated with significantly fewer adverse reactions compared with the traditional three-bag 20.25-hour regimen (low quality of evidence). All Trial Sequential Analyses showed lack of sufficient power. Children were not included in the majority of trials. Hence, the evidence pertains only to adults. These results highlight the paucity of randomised clinical trials comparing different interventions for paracetamol overdose and their routes of administration and the low or very low level quality of the evidence that is available. Evidence from a single trial found activated charcoal seemed the best choice to reduce absorption of paracetamol. Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure. Further randomised clinical trials with low risk of bias and adequate number of participants are required to determine which regimen results in the fewest adverse effects with the best efficacy. Current management of paracetamol poisoning worldwide involves the administration of intravenous or oral acetylcysteine which is based mainly on observational studies. Results from these observational studies indicate that treatment with acetylcysteine seems to result in a decrease in morbidity and mortality, However, further evidence from randomised clinical trials comparing different treatments are needed.

A diet and physical activity intervention for preventing weight retention among Taiwanese childbearing women: a randomised controlled trial.

PubMed

Huang, Tzu-ting; Yeh, Chieh-Ying; Tsai, Yc-Chen

2011-04-01

to examine the effect of individual counselling on diet and physical activity from pregnancy to six months post partum, or from birth to six months post partum, on weight retention among Taiwanese women. a randomised controlled trial assigned participants to two experimental groups [from pregnancy to six months post partum (EP) and from birth to six months post partum (EPP)] and one comparison group. a 3900-bed medical centre in northern Taiwan with around 3000 births annually. a sample of 189 women who had regular check-ups during pregnancy and gave birth at the medical centre. the comparison group received the routine outpatient department obstetric educational programme. The EP group attended regularly scheduled clinic visits with individualised dietary and physical activity education plans from 16 gestational weeks to six months post partum, and received on brochure. The EPP group received the same educational intervention as the EP group from 24-48 hours after birth to six months post partum. body weight, body mass index, health-promoting behaviour and psycho-social variables (self-efficacy, body image, depression and social support). average gestational weight gain was 14.02, 15.27 and 16.22 kg in the three EP, EPP and comparison groups respectively, and average weight retention at six months post partum was 2.34, 4.06 and 5.08 kg in the three groups, respectively. a diet and physical activity intervention from pregnancy is effective for reducing post-pregnancy weight retention. the findings of the present study should be taken into consideration when incorporating significant others and weight-loss maintenance strategies with interventions for a healthier family lifestyle. Copyright © 2009 Elsevier Ltd. All rights reserved.

Comparison of rheumatoid arthritis clinical trial outcome measures: a simulation study.

PubMed

Anderson, Jennifer J; Bolognese, James A; Felson, David T

2003-11-01

Isolated studies have suggested that continuous measures of response may be better than predefined, dichotomous definitions (e.g., the American College of Rheumatology 20% improvement criteria [ACR20]) for discriminating between rheumatoid arthritis (RA) treatments. Our goal was to determine the statistical power of predefined dichotomous outcome measures (termed "a priori"), compared with that of continuous measures derived from trial data in which there was no predefined response threshold (termed "data driven"), and to evaluate the sensitivity to change of these measures in the context of different treatments and early versus later-stage disease. In order to generalize beyond results from a single trial, we performed simulation studies. We obtained summary data from trials comparing disease-modifying antirheumatic drugs (DMARDs) and from comparative coxib-placebo trials to test the power of 2 a priori outcomes, the ACR20 and improvement of the Disease Activity Score (DDAS), as well as 2 data-driven outcomes. We studied patients with early RA and those with later-stage RA (duration of <4 years and 4-9 years, respectively). We performed simulation studies, using the interrelationship of ACR core set measures in the trials to generate multiple trial data sets consistent with the original data. The data-driven outcomes had greater power than did the a priori measures. The DMARD comparison was more powerful in early disease than in later-stage disease (the sample sizes needed to achieve 80% power for the most powerful test were 64 for early disease versus 100 for later disease), but the coxib-versus-placebo comparison was less powerful in early disease than in later disease (the sample sizes needed to achieve 80% power were 200 and 100, respectively). When the effects of treatment on core set items were small and/or inconsistent, power was reduced, particularly for a less broadly based outcome (e.g., DDAS) compared with the ACR20. The simulation studies demonstrate that data-driven outcome definitions can provide better sensitivity to change than does the ACR20 or DDAS. Using such methods would improve power, but at the expense of trial standardization. The studies also show how patient population and treatment characteristics affect the power of specific outcome measures in RA clinical trials, and provide quantification of those effects.

Impact of managed care on cancer trial enrollment.

PubMed

Gross, C P; Krumholz, H M

2005-06-01

To determine the relationship between managed care market activity and cancer trial enrollment. Trial participant data were obtained from the National Cancer Institute. Participants in cooperative group trials of breast, colorectal, lung, or prostate cancer during the years 1996 through 2001 were assigned to counties based on their zip code of residence. Linear regression was used to determine the relationship between county enrollment rate and two measures of county managed care activity (penetration and index of competition [IOC]), adjusting for other county characteristics. In bivariate analysis, there was a strong inverse correlation between trial enrollment rate and IOC (r = -0.23; P < .001) as well as the proportion of the population uninsured (-0.31; P < .001) and the percentage below poverty (-0.16; P < .001). In the multivariate model, greater county managed care competition (IOC) was inversely related to trial enrollment rate (P < .008 for comparison of each quartile v lowest quartile) after accounting for managed care penetration, proportion uninsured, and other county characteristics. Counties in the lowest quartile of managed care penetration tended to have lower enrollment rates than the remaining counties (r = -0.05; P = .048), while counties in the second, third, and fourth quartiles of penetration all had similar enrollment rates to one another. Cancer trial enrollment rates were suboptimal across all counties, and counties with higher levels of managed care competition had significantly lower enrollment rates. The relationship between managed care penetration and trial enrollment was less consistent. Future efforts to enhance trial participation should address the potential negative influence of market factors.

[Augmentin in the clinical picture of infectious diseases].

PubMed

Gracheva, N M; Petrova, M S; Avakov, A A; Bobovnikova, V T

1992-09-01

Augmentin is a new combination manufactured by Smith Kline Beecham (Great Britain). It is composed of amoxycillin and clavulanic acid and has antibacterial activity. Augmentin was used in clinical trials in the therapy of 50 adult patients with suppurations after surgical operations on the organs of the abdominal cavity, general staphylococcal infections, pneumonia and prophylactically during the preoperative period. It was also used in the treatment of 30 children patients with bronchopulmonary affections and inflammatory otorhinolaryngological diseases. The clinical trials were performed in the Clinic of Infectious Diseases of the N. G. Gabrichevskiĭ Moscow Research Institute of Epidemiology and Microbiology. For comparison ampicillin was used in the trials. Augmentin was shown to be an efficient formulation with antibacterial activity which could be successfully used in the parenteral therapy of severe affections due to organisms sensitive to it. In the treatment of the children patients with pneumonia augmentin by its therapeutic efficacy proved to be superior to ampicillin. The tolerance of augmentin was good.

Separating the Laparoscopic Camera Cord From the Monopolar "Bovie" Cord Reduces Unintended Thermal Injury From Antenna Coupling: A Randomized Controlled Trial.

PubMed

Robinson, Thomas N; Jones, Edward L; Dunn, Christina L; Dunne, Bruce; Johnson, Elizabeth; Townsend, Nicole T; Paniccia, Alessandro; Stiegmann, Greg V

2015-06-01

The monopolar "Bovie" is used in virtually every laparoscopic operation. The active electrode and its cord emit radiofrequency energy that couples (or transfers) to nearby conductive material without direct contact. This phenomenon is increased when the active electrode cord is oriented parallel to another wire/cord. The parallel orientation of the "Bovie" and laparoscopic camera cords cause transfer of energy to the camera cord resulting in cutaneous burns at the camera trocar incision. We hypothesized that separating the active electrode/camera cords would reduce thermal injury occurring at the camera trocar incision in comparison to parallel oriented active electrode/camera cords. In this prospective, blinded, randomized controlled trial, patients undergoing standardized laparoscopic cholecystectomy were randomized to separated active electrode/camera cords or parallel oriented active electrode/camera cords. The primary outcome variable was thermal injury determined by histology from skin biopsied at the camera trocar incision. Eighty-four patients participated. Baseline demographics were similar in the groups for age, sex, preoperative diagnosis, operative time, and blood loss. Thermal injury at the camera trocar incision was lower in the separated versus parallel group (31% vs 57%; P = 0.027). Separation of the laparoscopic camera cord from the active electrode cord decreases thermal injury from antenna coupling at the camera trocar incision in comparison to the parallel orientation of these cords. Therefore, parallel orientation of these cords (an arrangement promoted by integrated operating rooms) should be abandoned. The findings of this study should influence the operating room setup for all laparoscopic cases.

Separating Spike Count Correlation from Firing Rate Correlation

PubMed Central

Vinci, Giuseppe; Ventura, Valérie; Smith, Matthew A.; Kass, Robert E.

2016-01-01

Populations of cortical neurons exhibit shared fluctuations in spiking activity over time. When measured for a pair of neurons over multiple repetitions of an identical stimulus, this phenomenon emerges as correlated trial-to-trial response variability via spike count correlation (SCC). However, spike counts can be viewed as noisy versions of firing rates, which can vary from trial to trial. From this perspective, the SCC for a pair of neurons becomes a noisy version of the corresponding firing-rate correlation (FRC). Furthermore, the magnitude of the SCC is generally smaller than that of the FRC, and is likely to be less sensitive to experimental manipulation. We provide statistical methods for disambiguating time-averaged drive from within-trial noise, thereby separating FRC from SCC. We study these methods to document their reliability, and we apply them to neurons recorded in vivo from area V4, in an alert animal. We show how the various effects we describe are reflected in the data: within-trial effects are largely negligible, while attenuation due to trial-to-trial variation dominates, and frequently produces comparisons in SCC that, because of noise, do not accurately reflect those based on the underlying FRC. PMID:26942746

Inconsistency between direct and indirect comparisons of competing interventions: meta-epidemiological study.

PubMed

Song, Fujian; Xiong, Tengbin; Parekh-Bhurke, Sheetal; Loke, Yoon K; Sutton, Alex J; Eastwood, Alison J; Holland, Richard; Chen, Yen-Fu; Glenny, Anne-Marie; Deeks, Jonathan J; Altman, Doug G

2011-08-16

To investigate the agreement between direct and indirect comparisons of competing healthcare interventions. Meta-epidemiological study based on sample of meta-analyses of randomised controlled trials. Data sources Cochrane Database of Systematic Reviews and PubMed. Inclusion criteria Systematic reviews that provided sufficient data for both direct comparison and independent indirect comparisons of two interventions on the basis of a common comparator and in which the odds ratio could be used as the outcome statistic. Inconsistency measured by the difference in the log odds ratio between the direct and indirect methods. The study included 112 independent trial networks (including 1552 trials with 478,775 patients in total) that allowed both direct and indirect comparison of two interventions. Indirect comparison had already been explicitly done in only 13 of the 85 Cochrane reviews included. The inconsistency between the direct and indirect comparison was statistically significant in 16 cases (14%, 95% confidence interval 9% to 22%). The statistically significant inconsistency was associated with fewer trials, subjectively assessed outcomes, and statistically significant effects of treatment in either direct or indirect comparisons. Owing to considerable inconsistency, many (14/39) of the statistically significant effects by direct comparison became non-significant when the direct and indirect estimates were combined. Significant inconsistency between direct and indirect comparisons may be more prevalent than previously observed. Direct and indirect estimates should be combined in mixed treatment comparisons only after adequate assessment of the consistency of the evidence.

Inconsistency between direct and indirect comparisons of competing interventions: meta-epidemiological study

PubMed Central

Xiong, Tengbin; Parekh-Bhurke, Sheetal; Loke, Yoon K; Sutton, Alex J; Eastwood, Alison J; Holland, Richard; Chen, Yen-Fu; Glenny, Anne-Marie; Deeks, Jonathan J; Altman, Doug G

2011-01-01

Objective To investigate the agreement between direct and indirect comparisons of competing healthcare interventions. Design Meta-epidemiological study based on sample of meta-analyses of randomised controlled trials. Data sources Cochrane Database of Systematic Reviews and PubMed. Inclusion criteria Systematic reviews that provided sufficient data for both direct comparison and independent indirect comparisons of two interventions on the basis of a common comparator and in which the odds ratio could be used as the outcome statistic. Main outcome measure Inconsistency measured by the difference in the log odds ratio between the direct and indirect methods. Results The study included 112 independent trial networks (including 1552 trials with 478 775 patients in total) that allowed both direct and indirect comparison of two interventions. Indirect comparison had already been explicitly done in only 13 of the 85 Cochrane reviews included. The inconsistency between the direct and indirect comparison was statistically significant in 16 cases (14%, 95% confidence interval 9% to 22%). The statistically significant inconsistency was associated with fewer trials, subjectively assessed outcomes, and statistically significant effects of treatment in either direct or indirect comparisons. Owing to considerable inconsistency, many (14/39) of the statistically significant effects by direct comparison became non-significant when the direct and indirect estimates were combined. Conclusions Significant inconsistency between direct and indirect comparisons may be more prevalent than previously observed. Direct and indirect estimates should be combined in mixed treatment comparisons only after adequate assessment of the consistency of the evidence. PMID:21846695

Effective nationwide school-based participatory extramural program on adolescent body mass index, health knowledge and behaviors.

PubMed

Heo, Moonseong; Jimenez, Camille C; Lim, Jean; Isasi, Carmen R; Blank, Arthur E; Lounsbury, David W; Fredericks, Lynn; Bouchard, Michelle; Faith, Myles S; Wylie-Rosett, Judith

2018-01-16

Adolescent obesity is a major public health concern. Open to all high school students regardless of weight status, HealthCorps is a nationwide program offering a comprehensive high school-based participatory educational program to indirectly address obesity. We tested a hypothesis that the HealthCorps program would decrease BMI z-scores among overweight or obese students, and reduce obesity rates, and evaluated its effects on health knowledge and behaviors. HealthCorps aimed to improve student knowledge and behaviors regarding nutrition quality, physical activity, sleep, breakfast intake, and mental resilience. Participating students received through HealthCorps coordinators weekly or bi-weekly classroom lessons either for a semester or a year in addition to various during- and after-school health-promoting activities and mentorship. Self-reported height and weight were collected along with questionnaires assessing knowledge and behaviors during 2013-2014 academic year among 14 HealthCorps-participating New York City high schools. This quasi experimental two-arm pre-post trial included 611 HealthCorps and 221 comparison arm students for the analytic sample. Sex-specific analyses stratified by weight status were adjusted for age and Hispanic ethnicity with clustering effects of schools and students taken into account. HealthCorps female overweight/obese and obese student had a significant decrease in BMI z-scores (post-pre delta BMI z-score = -0.16 (95%CI = (-0.26, -0.05), p = 0.004 for the former; and = -0.23 (-0.44, -0.03), p = 0.028, for the latter) whereas comparison female counterparts did not. The HealthCorps students, but not the comparison students, had a significant increase for all knowledge domains except for the breakfast realm, and reported a greater number of significant behavior changes including fruit and vegetable intake and physical activities. The HealthCorps program was associated with reduced BMI z-score in overweight/obese and obese female adolescents, with enhanced health knowledge and behavior for both sexes. With its wide reach, this may be a promising program to help combat adolescent obesity in schools. This study is registered as a clinical trial at the ClinicalTrials.gov registry with trial number NCT02277496 on September 10, 2014 (Retrospectively registered).

Paired-housing selectively facilitates within-session extinction of avoidance behavior, and increases c-Fos expression in the medial prefrontal cortex, in anxiety vulnerable Wistar-Kyoto rats.

PubMed

Smith, Ian M; Pang, Kevin C H; Servatius, Richard J; Jiao, Xilu; Beck, Kevin D

2016-10-01

The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC). One means of reducing physiological responses to anxiety, and conditioned fear, in social species is the presence of a conspecific animal. The current study investigates whether or not pair-housed WKY rats would show facilitated extinction of avoidance in comparison to individual-housed WKY rats, and whether or not pair-housing influences mPFC activation during lever-press avoidance. Male WKY rats were assigned to individual-housed and pair-housed conditions. Rats were trained in lever-press avoidance. Each session of lever-press avoidance consisted of 20 trials, where pressing a lever in response to a warning tone prevented foot-shocks. Rats received 12 acquisition sessions over 4weeks; followed by 6 extinction sessions over 2weeks, where foot-shocks ceased to be delivered. Brains were harvested 90min after trials 1 and 10 of extinction sessions 1 and 6, and mPFC sections underwent c-Fos staining as a measure of activation. Pair-housed rats showed facilitated lever-press avoidance extinction rates, but the main cause for this overall difference was a selective facilitation of within-session extinction. Similar to individual-housed rats, pair-housed rats continued to avoid during trial 1 of extinction even when the avoidance responding had been significantly reduced by the end of the previous session. Pair-housed rats sacrificed on trial 1 showed greater c-Fos expression in the anterior cingulate cortex and prelimbic cortex subregions of the mPFC compared individual-housed rats sacrificed on trial 1. This data shows pair-housing to facilitate the extinction of avoidance, and to influence activity of the mPFC, in WKY rats. Despite this environmental manipulation, the pair-housed WKY rats continued to show avoidance responding on trial 1 of extinction sessions. This demonstrates that within-session extinction can be dissociated from between-session extinction-resistance in WKY rats. Furthermore, it suggests the individual-housing of WKY rats selectively slows within-session extinction, possibly by reducing neuronal activity of the mPFC during the testing situation. Published by Elsevier Inc.

Dose finding with the sequential parallel comparison design.

PubMed

Wang, Jessie J; Ivanova, Anastasia

2014-01-01

The sequential parallel comparison design (SPCD) is a two-stage design recommended for trials with possibly high placebo response. A drug-placebo comparison in the first stage is followed in the second stage by placebo nonresponders being re-randomized between drug and placebo. We describe how SPCD can be used in trials where multiple doses of a drug or multiple treatments are compared with placebo and present two adaptive approaches. We detail how to analyze data in such trials and give recommendations about the allocation proportion to placebo in the two stages of SPCD.

A mixed treatment comparison of gabapentin enacarbil, pramipexole, ropinirole and rotigotine in moderate-to-severe restless legs syndrome.

PubMed

Sun, Ying; van Valkenhoef, Gert; Morel, Thomas

2014-11-01

A mixed treatment comparison (MTC) was performed to investigate the relative efficacy and safety of licensed pharmaceuticals for moderate-to-severe restless legs syndrome (RLS). RLS trials published over the past 10 years were identified via systematic literature searches of MEDLINE, Embase, Cochrane CENTRAL, and manufacturers' websites. MTC was performed with WinBUGS software using a Bayesian approach. Identified primary outcomes: change in International RLS Study Group Rating Scale (IRLS) at week 12 and end of maintenance (EoM). IRLS and Clinical Global Impression - Improvement Scale (CGI-I) responders, RLS-6 items and adverse events (AEs). Twenty-eight clinical trials were identified. Fifteen were included in the primary analysis. Indirect comparisons were established among gabapentin enacarbil, pramipexole, ropinirole, rotigotine and placebo. Overall, the four active treatments showed similar efficacies as assessed by changes in IRLS scores, IRLS responders, CGI-I responders, and RLS-6 scores. The sole exception was change in IRLS at week 12, for which rotigotine was likely more efficacious than ropinirole (mean difference: -2.52 [95% CrI: -4.74, -0.40]). Indirect comparisons on safety endpoints indicated ropinirole was associated with a higher risk of nausea than the other agents, and was more likely to result in discontinuations due to lack of efficacy than pramipexole. Nausea was likely more frequent with pramipexole than gabapentin enacarbil, and rotigotine was more likely to result in discontinuation due to AEs than ropinirole and pramipexole. This MTC confirmed the superiority of gabapentin enacarbil, pramipexole, ropinirole, and rotigotine above placebo in alleviating RLS symptoms. Compared to ropinirole, rotigotine showed some additional benefit in terms of change in IRLS at Week 12. Choice of RLS drugs requires careful evaluation of effectiveness and safety profiles in clinical practice. Due to lack of head-to-head trials, inconsistency could not be assessed in our analysis. Head-to-head trials on a more homogeneous population are needed to validate the MTC results.

Comprehensive nutrition and lifestyle education improves weight loss and physical activity in Hispanic Americans following gastric bypass surgery: a randomized controlled trial.

PubMed

Nijamkin, Monica Petasne; Campa, Adriana; Sosa, Jorge; Baum, Marianna; Himburg, Susan; Johnson, Paulette

2012-03-01

As morbid obesity increasingly affects Hispanic Americans, the incidence of bariatric procedures among this population is rising. Despite this, prospective research on the effects of comprehensive postoperative education-centered interventions on weight loss and physical activity focused on Hispanic Americans is lacking. To examine whether a comprehensive nutrition education and behavior modification intervention improves weight loss and physical activity in Hispanic Americans with obesity following Roux-en-Y gastric bypass surgery (RYGB). A prospective randomized-controlled trial was conducted between November 2008 and April 2010. At 6 months following RYGB, 144 Hispanic Americans with obesity were randomly assigned to a comprehensive nutrition and lifestyle educational intervention (n=72) or a noncomprehensive approach (comparison group n=72). Those in the comprehensive group received education sessions every other week for 6 weeks in small groups and frequent contact with a registered dietitian. Those in the comparison group received brief, printed healthy lifestyle guidelines. Patients were reassessed at 12 months following surgery. Main outcome measures were excess weight loss and physical activity changes over time. Statistical analyses used t test, ?(2) test, Wilcoxon signed rank, Mann-Whitney U test, and intent-to-treat analysis, significance P<0.05. Participants (mean age 44.5 ± 13.5 years) were mainly Cuban-born women (83.3%). Mean preoperative excess weight and body mass index (calculated as kg/m(2)) were 72.20 ± 27.81 kg and 49.26 ± 9.06, respectively. At 12 months following surgery, both groups lost weight significantly, but comprehensive group participants experienced greater excess weight loss (80% vs 64% from preoperative excess weight; P<0.001) and greater body mass index reduction (6.48 ± 4.37 vs 3.63 ± 3.41; P<0.001) than comparison group participants. Comprehensive group participants were significantly more involved in physical activity (+14 min/wk vs ?4 min/wk; P<0.001) than comparison group participants. Mean protein intake was significantly lower in the comparison group than that in the comprehensive group (P<0.024). Findings support the importance of comprehensive nutrition education for achieving more effective weight reduction in Hispanic Americans following RYGB. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Methodological problems in the use of indirect comparisons for evaluating healthcare interventions: survey of published systematic reviews.

PubMed

Song, Fujian; Loke, Yoon K; Walsh, Tanya; Glenny, Anne-Marie; Eastwood, Alison J; Altman, Douglas G

2009-04-03

To investigate basic assumptions and other methodological problems in the application of indirect comparison in systematic reviews of competing healthcare interventions. Survey of published systematic reviews. Inclusion criteria Systematic reviews published between 2000 and 2007 in which an indirect approach had been explicitly used. Identified reviews were assessed for comprehensiveness of the literature search, method for indirect comparison, and whether assumptions about similarity and consistency were explicitly mentioned. The survey included 88 review reports. In 13 reviews, indirect comparison was informal. Results from different trials were naively compared without using a common control in six reviews. Adjusted indirect comparison was usually done using classic frequentist methods (n=49) or more complex methods (n=18). The key assumption of trial similarity was explicitly mentioned in only 40 of the 88 reviews. The consistency assumption was not explicit in most cases where direct and indirect evidence were compared or combined (18/30). Evidence from head to head comparison trials was not systematically searched for or not included in nine cases. Identified methodological problems were an unclear understanding of underlying assumptions, inappropriate search and selection of relevant trials, use of inappropriate or flawed methods, lack of objective and validated methods to assess or improve trial similarity, and inadequate comparison or inappropriate combination of direct and indirect evidence. Adequate understanding of basic assumptions underlying indirect and mixed treatment comparison is crucial to resolve these methodological problems. APPENDIX 1: PubMed search strategy. APPENDIX 2: Characteristics of identified reports. APPENDIX 3: Identified studies. References of included studies.

[Assessment on the short-term impact regarding the community-based interventions to improve physical activities in three urban areas of Hangzhou city].

PubMed

Gao, Fang; Liu, Qing-min; Ren, Yan-jun; He, Ping-ping; LV, Jun; Li, Li-ming

2013-06-01

To evaluate the short-term impact of comprehensive community based intervention on physical activity (PA) of adults living in the three urban communities of Hangzhou city. Within the framework of Community Interventions for Health (CIH) Program, a community trial was conducted in two urban areas (Xiacheng district and Gongshu district)and an urban area(Xihu district)as control, by a parallel comparison and random grouping based quasi-experimental design. Two independent questionnaire-based surveys of cross-sectional samples in the intervention and comparison areas were used to assess the short-term impact of the intervention program. A total of 2016 adults at baseline and 2016 adults at follow-up stages, completed the survey, including 1016 adults from the intervention areas and 1000 from the comparison area. Over the two-year intervention period, the cognitive level on benefits of physical activity in the intervention areas were trending downward. The changes observed in the comparison area did not show statistical significance. Intervention areas showed a statistically significant increase (1204 vs. 1386, P = 0.023) in the level of physical activity(metabolic equivalent, MET-minutes/week)compared with the comparison area(918 vs. 924, P = 0.201). And results remained the same after eliminating the possible effects of age factor. After a two-year intervention, beneficial changes were noted in the intervention areas with respect to the level of physical activity. A community-based intervention program on physical activity seemed feasible and effective in the urban areas of Hangzhou.

An adaptive, individualized fMRI delay discounting procedure to increase flexibility and optimize scanner time.

PubMed

Koffarnus, Mikhail N; Deshpande, Harshawardhan U; Lisinski, Jonathan M; Eklund, Anders; Bickel, Warren K; LaConte, Stephen M

2017-11-01

Research on the rate at which people discount the value of future rewards has become increasingly prevalent as discount rate has been shown to be associated with many unhealthy patterns of behavior such as drug abuse, gambling, and overeating. fMRI research points to a fronto-parietal-limbic pathway that is active during decisions between smaller amounts of money now and larger amounts available after a delay. Researchers in this area have used different variants of delay discounting tasks and reported various contrasts between choice trials of different types from these tasks. For instance, researchers have compared 1) choices of delayed monetary amounts to choices of the immediate monetary amounts, 2) 'hard' choices made near one's point of indifference to 'easy' choices that require little thought, and 3) trials where an immediate choice is available versus trials where one is unavailable, regardless of actual eventual choice. These differences in procedure and analysis make comparison of results across studies difficult. In the present experiment, we designed a delay discounting task with the intended capability of being able to construct contrasts of all three comparisons listed above while optimizing scanning time to reduce costs and avoid participant fatigue. This was accomplished with an algorithm that customized the choice trials presented to each participant with the goal of equalizing choice trials of each type. We compared this task, which we refer to here as the individualized discounting task (IDT), to two other delay discounting tasks previously reported in the literature (McClure et al., 2004; Amlung et al., 2014) in 18 participants. Results show that the IDT can examine each of the three contrasts mentioned above, while yielding a similar degree of activation as the reference tasks. This suggests that this new task could be used in delay discounting fMRI studies to allow researchers to more easily compare their results to a majority of previous research while minimizing scanning duration. Copyright © 2017 Elsevier Inc. All rights reserved.

Interventions for treating inadvertent postoperative hypothermia.

PubMed

Warttig, Sheryl; Alderson, Phil; Campbell, Gillian; Smith, Andrew F

2014-11-20

Inadvertent postoperative hypothermia (a drop in core body temperature to below 36°C) occurs as an effect of surgery when anaesthetic drugs and exposure of the skin for long periods of time during surgery result in interference with normal temperature regulation. Once hypothermia has occurred, it is important that patients are rewarmed promptly to minimise potential complications. Several different interventions are available for rewarming patients. To estimate the effectiveness of treating inadvertent perioperative hypothermia through postoperative interventions to decrease heat loss and apply passive and active warming systems in adult patients who have undergone surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE (Ovid SP) (1956 to 21 February 2014), EMBASE (Ovid SP) (1982 to 21 February 2014), the Institute for Scientific Information (ISI) Web of Science (1950 to 21 February 2014) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EBSCO host (1980 to 21 February 2014), as well as reference lists of articles. We also searched www.controlled-trials.com and www.clincialtrials.gov. Randomized controlled trials of postoperative warming interventions aiming to reverse hypothermia compared with control or with each other. Three review authors identified studies for inclusion in this review. One review author extracted data and completed risk of bias assessments; two review authors checked the details. Meta-analysis was conducted when appropriate by using standard methodological procedures as expected by The Cochrane Collaboration. We included 11 trials with 699 participants. Ten trials provided data for analysis. Trials varied in the numbers and types of participants included and in the types of surgery performed. Most trials were at high or unclear risk of bias because of inappropriate or unclear randomization procedures, and because blinding of assessors and participants generally was not possible. This may have influenced results, but it is unclear how the results may have been influenced. Active warming was found to reduce the mean time taken to achieve normothermia by about 30 minutes in comparison with use of warmed cotton blankets (mean difference (MD) -32.13 minutes, 95% confidence interval (CI) -42.55 to -21.71; moderate-quality evidence), but no significant difference in shivering was noted. Active warming was found to reduce mean time taken to achieve normothermia by almost an hour and a half in comparison with use of unwarmed cotton blankets (MD -88.86 minutes, 95% CI -123.49 to -54.23; moderate-quality evidence), and people in the active warming group were less likely to shiver than those in the unwarmed cotton blanket group (Relative Risk=0.61 95% CI= 0.42 to 0.86; low quality evidence). There was no effect on mean temperature difference in degrees celsius at 60 minutes (MD=0.18°C, 95% CI=-0.10 to 0.46; moderate quality evidence), and no data were available in relation to major cardiovascular complications. Forced air warming was found to reduce time taken to achieve normothermia by about one hour in comparison to circulating hot water devices (MD=-54.21 minutes 95% CI= -94.95, -13.47). There was no statistically significant difference between thermal insulation and cotton blankets on mean time to achieve normothermia (MD =-0.29 minutes, 95% CI=-25.47 to 24.89; moderate quality evidence) or shivering (Relative Risk=1.36 95% CI= 0.69 to 2.67; moderate quality evidence), and no data were available for mean temperature difference or major cardiovascular complications. Insufficient evidence was available about other comparisons, adverse effects or any other secondary outcomes. Active warming, particularly forced air warming, appears to offer a clinically important reduction in mean time taken to achieve normothermia (normal body temperature between 36°C and 37.5°C) in patients with postoperative hypothermia. However, high-quality evidence on other important clinical outcomes is lacking; therefore it is unclear whether active warming offers other benefits and harms. High-quality evidence on other warming methods is also lacking; therefore it is unclear whether other rewarming methods are effective in reversing postoperative hypothermia.

A community trial of the impact of improved sexually transmitted disease treatment on the HIV epidemic in rural Tanzania: 2. Baseline survey results.

PubMed

Grosskurth, H; Mosha, F; Todd, J; Senkoro, K; Newell, J; Klokke, A; Changalucha, J; West, B; Mayaud, P; Gavyole, A

1995-08-01

To determine baseline HIV prevalence in a trial of improved sexually transmitted disease (STD) treatment, and to investigate risk factors for HIV. To assess comparability of intervention and comparison communities with respect to HIV/STD prevalence and risk factors. To assess adequacy of sample size. Twelve communities in Mwanza Region, Tanzania: one matched pair of roadside communities, four pairs of rural communities, and one pair of island communities. One community from each pair was randomly allocated to receive the STD intervention following the baseline survey. Approximately 1000 adults aged 15-54 years were randomly sampled from each community. Subjects were interviewed, and HIV and syphilis serology performed. Men with a positive leucocyte esterase dipstick test on urine, or reporting a current STD, were tested for urethral infections. A total of 12,534 adults were enrolled. Baseline HIV prevalences were 7.7% (roadside), 3.8% (rural) and 1.8% (islands). Associations were observed with marital status, injections, education, travel, history of STD and syphilis serology. Prevalence was higher in circumcised men, but not significantly after adjusting for confounders. Intervention and comparison communities were similar in the prevalence of HIV (3.8 versus 4.4%), active syphilis (8.7 versus 8.2%), and most recorded risk factors. Within-pair variability in HIV prevalence was close to the value assumed for sample size calculations. The trial cohort was successfully established. Comparability of intervention and comparison communities at baseline was confirmed for most factors. Matching appears to have achieved a trial of adequate sample size. The apparent lack of a protective effect of male circumcision contrasts with other studies in Africa.

Effectiveness of Placebo Therapy for Maintaining Masking in a Clinical Trial of Vergence/Accommodative Therapy

PubMed Central

Kulp, Marjean; Mitchell, G. Lynn; Borsting, Eric; Scheiman, Mitchell; Cotter, Susan; Rouse, Michael; Tamkins, Susanna; Mohney, Brian G.; Toole, Andrew; Reuter, Kathleen

2009-01-01

Purpose To evaluate the effectiveness of the Convergence Insufficiency Treatment Trial (CITT) placebo therapy program in maintaining masking of patients randomized to the office-based treatment arms, determine whether demographic variables affect masking, and determine whether perception of assigned treatment group was associated with treatment outcome or adherence to treatment. Methods Patients (n = 221, ages, 9–17 years) were randomized to one of four treatment groups, two of which were office-based and masked to treatment (n = 114). The placebo therapy program was designed to appear to be real vergence/accommodative therapy, without stimulating vergence, accommodation, or fine saccades (beyond levels of daily visual activities). After treatment, patients in the office-based groups were asked whether they thought they had received real or placebo therapy and how confident they were in their answers. Results Ninety-three percent of patients assigned to real therapy and 85% assigned to placebo therapy thought they were in the real therapy group (P = 0.17). No significant differences were found between the two groups in adherence to the therapy (P ≥ 0.22 for all comparisons). The percentage of patients who thought they were assigned to real therapy did not differ by age, sex, race, or ethnicity (P > 0.30 for all comparisons). No association was found between patients' perception of group assignment and symptoms or signs at outcome (P ≥ 0.38 for all comparisons). Conclusions The CITT placebo therapy program was effective in maintaining patient masking in this study and therefore may have potential for use in future clinical trials using vergence/accommodative therapy. Masking was not affected by demographic variables. Perception of group assignment was not related to symptoms or signs at outcome (ClinicalTrials.gov number, NCT00338611). PMID:19151384

Multiple linear regression to estimate time-frequency electrophysiological responses in single trials

PubMed Central

Hu, L.; Zhang, Z.G.; Mouraux, A.; Iannetti, G.D.

2015-01-01

Transient sensory, motor or cognitive event elicit not only phase-locked event-related potentials (ERPs) in the ongoing electroencephalogram (EEG), but also induce non-phase-locked modulations of ongoing EEG oscillations. These modulations can be detected when single-trial waveforms are analysed in the time-frequency domain, and consist in stimulus-induced decreases (event-related desynchronization, ERD) or increases (event-related synchronization, ERS) of synchrony in the activity of the underlying neuronal populations. ERD and ERS reflect changes in the parameters that control oscillations in neuronal networks and, depending on the frequency at which they occur, represent neuronal mechanisms involved in cortical activation, inhibition and binding. ERD and ERS are commonly estimated by averaging the time-frequency decomposition of single trials. However, their trial-to-trial variability that can reflect physiologically-important information is lost by across-trial averaging. Here, we aim to (1) develop novel approaches to explore single-trial parameters (including latency, frequency and magnitude) of ERP/ERD/ERS; (2) disclose the relationship between estimated single-trial parameters and other experimental factors (e.g., perceived intensity). We found that (1) stimulus-elicited ERP/ERD/ERS can be correctly separated using principal component analysis (PCA) decomposition with Varimax rotation on the single-trial time-frequency distributions; (2) time-frequency multiple linear regression with dispersion term (TF-MLRd) enhances the signal-to-noise ratio of ERP/ERD/ERS in single trials, and provides an unbiased estimation of their latency, frequency, and magnitude at single-trial level; (3) these estimates can be meaningfully correlated with each other and with other experimental factors at single-trial level (e.g., perceived stimulus intensity and ERP magnitude). The methods described in this article allow exploring fully non-phase-locked stimulus-induced cortical oscillations, obtaining single-trial estimate of response latency, frequency, and magnitude. This permits within-subject statistical comparisons, correlation with pre-stimulus features, and integration of simultaneously-recorded EEG and fMRI. PMID:25665966

The experience of older patients with cancer in phase 1 clinical trials: a qualitative case series.

PubMed

Kvale, Elizabeth A; Woodby, Lesa; Williams, Beverly Rosa

2010-11-01

This article explores the experiences of older patients with cancer in phase 1 clinical trials. Conducting a case series of face-to-face, in-depth, open-ended interviews and using qualitative methods of analysis, we find that the psychosocial process of social comparison is relevant for understanding older adults' phase 1 clinical trial participation. Social comparison influences decisions to enroll in a phase 1 clinical trial, shapes perceptions of supportive care needs, and encourages the utilization of hope. Additional research should develop strategies for addressing supportive care needs among this patient cohort whose use of social comparison can inhibit articulation of pain, suffering, and symptom burden as well as use of informal support systems.

An mHealth App for Supporting Quitters to Manage Cigarette Cravings With Short Bouts of Physical Activity: A Randomized Pilot Feasibility and Acceptability Study

PubMed Central

Lintunen, Taru; Heikkinen, Risto; Vanhala, Mauno; Kettunen, Tarja

2017-01-01

Background While gains in reducing smoking rates in Finland have been made, prevalence rates are still substantial. Relapse rates among smokers engaged in quit-smoking programs are high. Physical activity has been proposed as one means to help smokers manage cravings. Software and apps on mobile phone and handheld devices offer an opportunity to communicate messages on how to use physical activity to manage cravings as part of quit-smoking programs. Objective We aimed to test the feasibility, acceptability, usability, and preliminary efficacy of an mHealth mobile phone app, Physical activity over Smoking (PhoS), to assist smokers in quitting smoking in a randomized controlled trial. The app was designed to prompt smokers to engage in physical activities to manage their smoking cravings. Methods Regular smokers (n=44) attended a group-based behavioral counselling program aimed at promoting physical activity as an additional aid to quit. After quit day, participants were randomly allocated to an intervention (n=25) or to a comparison (n=19) group. Participants in the intervention group were provided with the PhoS app and training on how to use it to assist with relapse prevention. Participants in the comparison condition were provided with generalized relapse prevention training. Results Some participants reported that the PhoS app was useful in assisting them to successfully manage their cigarette cravings, although compliance across the sample was modest and participants reported low levels of usability. Participants receiving the PhoS app did not report greater abstinence than those who did not receive the app. However, participants receiving the app were more likely to report greater abstinence if they did not use pharmacological support, while those who did not receive the app reported greater abstinence when using pharmacological support. Participants receiving the app reported greater levels of physical activity than those who did not. Results revealed that the app resulted in better retention. Conclusions The PhoS app showed some potential to reduce abstinence among participants not using pharmacological therapy and to increase physical activity. However, problems with usability and lack of effects on abstinence raise questions over the app’s long-term effectiveness. Future research should prioritize further development of the app to maximize usability and test effects of the intervention independent of quit-smoking programs. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 55259451; http://www.controlled-trials.com/ISRCTN55259451 (Archived by WebCite at http://www.webcitation.org/6cKF2mzEI) PMID:28550004

Optimality, sample size, and power calculations for the sequential parallel comparison design.

PubMed

Ivanova, Anastasia; Qaqish, Bahjat; Schoenfeld, David A

2011-10-15

The sequential parallel comparison design (SPCD) has been proposed to increase the likelihood of success of clinical trials in therapeutic areas where high-placebo response is a concern. The trial is run in two stages, and subjects are randomized into three groups: (i) placebo in both stages; (ii) placebo in the first stage and drug in the second stage; and (iii) drug in both stages. We consider the case of binary response data (response/no response). In the SPCD, all first-stage and second-stage data from placebo subjects who failed to respond in the first stage of the trial are utilized in the efficacy analysis. We develop 1 and 2 degree of freedom score tests for treatment effect in the SPCD. We give formulae for asymptotic power and for sample size computations and evaluate their accuracy via simulation studies. We compute the optimal allocation ratio between drug and placebo in stage 1 for the SPCD to determine from a theoretical viewpoint whether a single-stage design, a two-stage design with placebo only in the first stage, or a two-stage design is the best design for a given set of response rates. As response rates are not known before the trial, a two-stage approach with allocation to active drug in both stages is a robust design choice. Copyright © 2011 John Wiley & Sons, Ltd.

Meta-analysis of Dropout in Treatments for Post-traumatic Stress Disorder

PubMed Central

Imel, Zac E.; Laska, Kevin; Jakcupcak, Matthew; Simpson, Tracy L.

2013-01-01

Objective Many patients dropout of treatments for Post-traumatic stress disorder (PTSD) and some clinicians believe that ‘trauma focused’ treatments increase dropout. Method We conducted a meta-analysis of dropout among active treatments in clinical trials for PTSD (42 studies; 17 direct comparisons). Results The average dropout rate was 18%, but it varied significantly across studies. Group modality and greater number of sessions, but not trauma focus, predicted increased dropout. When the meta-analysis was restricted to direct comparisons of active treatments, there were no differences in dropout. Differences in trauma focus between treatments in the same study did not predict dropout. However, trauma focused treatments resulted in higher dropout as compared to Present Centered Therapy (PCT) – a treatment originally designed as a control, but now listed as a research supported intervention for PTSD. Conclusion Dropout varies between active interventions for PTSD across studies, but differences are primarily driven by differences between studies. There do not appear to be systematic differences across active interventions when they are directly compared in the same study. The degree of clinical attention placed on the traumatic event does not appear to be a primary cause of dropout from active treatments. However comparisons of PCT may be an exception to this general pattern, perhaps due to a restriction of variability in trauma focus among comparisons of active treatments. More research is needed comparing trauma focused interventions to trauma avoidant treatments such as PCT. PMID:23339535

Enhancing response inhibition by incentive: Comparison of adolescents with and without substance use disorder

PubMed Central

Chung, Tammy; Geier, Charles; Luna, Beatriz; Pajtek, Stefan; Terwilliger, Robert; Thatcher, Dawn; Clark, Duncan

2010-01-01

Effective response inhibition is a key component of recovery from addiction. Some research suggests that response inhibition can be enhanced through reward contingencies. We examined the effect of monetary incentive on response inhibition among adolescents with and without substance use disorder (SUD) using a fast event-related fMRI antisaccade reward task. The fMRI task permits investigation of how reward (monetary incentive) might modulate inhibitory control during three task phases: cue presentation (reward or neutral trial), response preparation, and response execution. Adolescents with lifetime SUD (n=12; 100% marijuana use disorder) were gender and age-matched to healthy controls (n=12). Monetary incentive facilitated inhibitory control for SUD adolescents; for healthy controls, the difference in error rate for neutral and reward trials was not significant. There were no significant differences in behavioral performance between groups across reward and neutral trials, however, group differences in regional brain activation were identified. During the response preparation phase of reward trials, SUD adolescents, compared to controls, showed increased activation of prefrontal and oculomotor control (e.g., frontal eye field) areas, brain regions that have been associated with effective response inhibition. Results indicate differences in brain activation between SUD and control youth when preparing to inhibit a prepotent response in the context of reward, and support a possible role for incentives in enhancing response inhibition among youth with SUD. PMID:21115229

Pazopanib: an oral multitargeted tyrosine kinase inhibitor for use in renal cell carcinoma.

PubMed

LaPlant, Kourtney D; Louzon, Paige D

2010-06-01

To summarize the currently available clinical data on pazopanib, as well as review the merits and adverse effects of pazopanib in the treatment of renal cell carcinoma (RCC). A literature search was performed of MEDLINE, PubMed, and the American Society of Clinical Oncology abstracts from January 1995 to February 2010, using the primary search terms pazopanib, GW786034, Votrient, and tyrosine kinase inhibitors. All available English-language articles and trials that described the pharmacokinetics, pharmacology, pharmacodynamics, clinical activity, or adverse effects of pazopanib were reviewed. Pazopanib is a second-generation multitargeted tyrosine kinase inhibitor (TKI) that has exhibited antiangiogenic and antitumor activity. Phase 1 clinical trials have established the safety and tolerability of pazopanib 800 mg orally daily. Phase 2 and 3 studies have shown promising activity in RCC, including treatment naïve or cytokine-pretreated patients, demonstrating a greater rate of total disease control with pazopanib compared to placebo. Activity has also been shown in a variety of other cancers, including ovarian cancer, non-small-cell lung cancer, breast cancer, and soft tissue sarcoma. The most common adverse effects of pazopanib include nausea, diarrhea, hypertension, hair depigmentation, and elevated transaminase levels. Adverse effects are most commonly Grades 1-2. Other Phase 3 trials are ongoing in RCC, including a comparison to sunitinib, another TKI used in RCC, as well as trials in other tumor types. Current data suggest pazopanib to be a viable treatment option as first-line therapy for advanced RCC. Data are awaited comparing pazopanib to other TKIs. Until results of head-to-head trials conducted of the various agents are available, it cannot be said whether pazopanib is more tolerable or efficacious than currently available therapies.

Optimizing a positive psychology intervention to promote health behaviors following an acute coronary syndrome: The Positive Emotions after Acute Coronary Events-III (PEACE-III) randomized factorial trial.

PubMed

Celano, Christopher M; Albanese, Ariana M; Millstein, Rachel A; Mastromauro, Carol A; Chung, Wei-Jean; Campbell, Kirsti A; Legler, Sean R; Park, Elyse R; Healy, Brian C; Collins, Linda M; Januzzi, James L; Huffman, Jeff C

2018-04-05

Despite the clear benefits of physical activity and related behaviors on prognosis, most patients suffering an acute coronary syndrome (ACS) remain nonadherent to these behaviors. Deficits in positive psychological constructs (e.g., optimism) are linked to reduced participation in health behaviors, supporting the potential utility of a positive psychology (PP)-based intervention in post-ACS patients. Accordingly, we aimed to identify optimal components of a PP-based intervention to promote post-ACS physical activity. As part of a multiphase optimization strategy, we completed a randomized factorial trial with eight conditions in 128 post-ACS patients to efficiently identify best-performing intervention components. All participants received a PP-based intervention, with conditions varying in duration (presence/absence of booster sessions), intensity (weekly/daily PP exercises), and content (PP alone or combined with motivational interviewing [MI]), allowing three concurrent comparisons within the trial. Study aims included assessments of the overall feasibility, acceptability, and impact of the intervention, along with the primary aim of determining which components were associated with objectively-measured physical activity and self-reported health behavior adherence at 16 weeks, assessed using longitudinal models. The intervention was well-accepted and associated with substantial improvements in behavioral and psychological outcomes. Booster sessions were associated with greater activity to a nearly significant degree (β=8.58, 95% confidence interval= -0.49-17.65, effect size difference=.43; p=.064), MI was associated with overall adherence (β=0.95, 95% confidence interval=0.02-1.87, effect size difference=.39; p=.044), and weekly exercise completion was generally superior to daily. These findings will enable optimization of the PP-based intervention in preparation for a well-powered controlled trial. ClinicalTrials.gov identifier: NCT02754895.

Bleeding and infection with external ventricular drainage: a systematic review in comparison with adjudicated adverse events in the ongoing Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-III IHV) trial.

PubMed

Dey, Mahua; Stadnik, Agnieszka; Riad, Fady; Zhang, Lingjiao; McBee, Nichol; Kase, Carlos; Carhuapoma, J Ricardo; Ram, Malathi; Lane, Karen; Ostapkovich, Noeleen; Aldrich, Francois; Aldrich, Charlene; Jallo, Jack; Butcher, Ken; Snider, Ryan; Hanley, Daniel; Ziai, Wendy; Awad, Issam A

2015-03-01

Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication. To analyze the rate of complications in the ongoing Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) trial, providing a comparison with a systematic review of complications of EVD in the literature. Patients were prospectively enrolled in the CLEAR III trial after placement of an EVD for obstructive intraventricular hemorrhage and randomized to receive recombinant tissue-type plasminogen activator or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on computed tomography scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled with STATA software. Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 patients enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced ≥1 new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis. Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the present study, rates of new bleeds and bacterial meningitis/ventriculitis are very low despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to >60 trial sites.

Regional brain activity that determines successful and unsuccessful working memory formation.

PubMed

Teramoto, Shohei; Inaoka, Tsubasa; Ono, Yumie

2016-08-01

Using EEG source reconstruction with Multiple Sparse Priors (MSP), we investigated the regional brain activity that determines successful memory encoding in two participant groups of high and low accuracy rates. Eighteen healthy young adults performed a sequential fashion of visual Sternberg memory task. The 32-channel EEG was continuously measured during participants performed two 70 trials of memory task. The regional brain activity corresponding to the oscillatory EEG activity in the alpha band (8-13 Hz) during encoding period was analyzed by MSP implemented in SPM8. We divided the data of all participants into 2 groups (low- and highperformance group) and analyzed differences in regional brain activity between trials in which participants answered correctly and incorrectly within each of the group. Participants in low-performance group showed significant activity increase in the visual cortices in their successful trials compared to unsuccessful ones. On the other hand, those in high-performance group showed a significant activity increase in widely distributed cortical regions in the frontal, temporal, and parietal areas including those suggested as Baddeley's working memory model. Further comparison of activated cortical volumes and mean current source intensities within the cortical regions of Baddeley's model during memory encoding demonstrated that participants in high-performance group showed enhanced activity in the right premotor cortex, which plays an important role in maintaining visuospatial attention, compared to those in low performance group. Our results suggest that better ability in memory encoding is associated with distributed and stronger regional brain activities including the premotor cortex, possibly indicating efficient allocation of cognitive load and maintenance of attention.

A randomized clinical trial in subjects with dry mouth evaluating subjective perceptions of an experimental oral gel, an oral rinse and a mouth spray compared to water.

PubMed

Jose, Anto; Siddiqi, Muhammad; Cronin, Matthew; DiLauro, Thomas S; Bosma, Mary Lynn

2016-02-01

This multicenter, randomized, parallel group study analyzed the effectiveness of an experimental oral gel, a commercially available oral rinse and a commercially available mouth spray versus water alone at relieving self-reported symptoms of dry mouth over a 28-day home use treatment period. The effects of the study treatments on dry mouth-related quality of life (QoL) were also investigated. Eligible subjects were stratified by dry mouth severity (mild, moderate or severe) and randomized to receive one of the study treatments. Prior to first use they completed a questionnaire designed to assess their baseline dry mouth-related QoL. Following first use and on Day 8 (2 hours post-treatment only) and Day 29, subjects completed the modified Product Performance and Attributes Questionnaire (PPAQ) I at 0.5, 1, 2 and 4 hours post-treatment. Subjects further assessed treatment performance using the PPAQ II questionnaire on Days 8 and 29 and the dry mouth-related QoL questionnaire on Day 29. In 396 randomized subjects almost all comparisons of responses to PPAQ I, including those for the primary endpoint (response to PPAQ I Question 1 'Relieving the discomfort of dry mouth' after 2 hours on Day 29), were statistically significant in favor of active treatment groups versus water (P < 0.05). All comparisons of responses to PPAQ II on Days 8 and 29 were statistically significant in favor of active treatments versus water (P < 0.05). Moreover, nearly all comparisons for dry mouth-related QoL scores on Day 29 were statistically significant in favor of the active treatments versus water. All the dry mouth management strategies in this trial were well tolerated.

Strength training alone, exercise therapy alone, and exercise therapy with passive manual mobilisation each reduce pain and disability in people with knee osteoarthritis: a systematic review.

PubMed

Jansen, Mariette J; Viechtbauer, Wolfgang; Lenssen, Antoine F; Hendriks, Erik J M; de Bie, Rob A

2011-01-01

What are the effects of strength training alone, exercise therapy alone, and exercise with additional passive manual mobilisation on pain and function in people with knee osteoarthritis compared to control? What are the effects of these interventions relative to each other? A meta-analysis of randomised controlled trials. Adults with osteoarthritis of the knee. INTERVENTION TYPES: Strength training alone, exercise therapy alone (combination of strength training with active range of motion exercises and aerobic activity), or exercise with additional passive manual mobilisation, versus any non-exercise control. Comparisons between the three interventions were also sought. The primary outcome measures were pain and physical function. 12 trials compared one of the interventions against control. The effect size on pain was 0.38 (95% CI 0.23 to 0.54) for strength training, 0.34 (95% CI 0.19 to 0.49) for exercise, and 0.69 (95% CI 0.42 to 0.96) for exercise plus manual mobilisation. Each intervention also improved physical function significantly. No randomised comparisons of the three interventions were identified. However, meta-regression indicated that exercise plus manual mobilisations improved pain significantly more than exercise alone (p = 0.03). The remaining comparisons between the three interventions for pain and physical function were not significant. Exercise therapy plus manual mobilisation showed a moderate effect size on pain compared to the small effect sizes for strength training or exercise therapy alone. To achieve better pain relief in patients with knee osteoarthritis physiotherapists or manual therapists might consider adding manual mobilisation to optimise supervised active exercise programs. Copyright © 2011 Australian Physiotherapy Association. Published by .. All rights reserved.

Exploring Mediators of Physical Activity in Young Adult Cancer Survivors: Evidence from a Randomized Trial of a Facebook-Based Physical Activity Intervention.

PubMed

Valle, Carmina G; Tate, Deborah F; Mayer, Deborah K; Allicock, Marlyn; Cai, Jianwen

2015-03-01

This study examined the effects of a physical activity (PA) intervention for young adult cancer survivors on changes in self-efficacy, social support, and self-monitoring and determined whether changes in these social cognitive theory constructs mediated the relationship between the intervention and changes in PA. A 12-week randomized trial compared a Facebook-based intervention (FITNET) aimed at increasing moderate-to-vigorous intensity PA to a Facebook-based self-help comparison group. Young adult cancer survivors (N=86, aged 21-39) were randomly assigned to one of the two groups. Self-report measures of PA and psychosocial variables were collected at baseline and after 12 weeks. The FITNET group reported lower self-efficacy for sticking to exercise (mean change=-0.38; 95% CI: -0.62 to -0.12; p=0.025) and social support from friends on social networking websites (mean change=-0.47; 95% CI: -1.45 to 0.65; p=0.039) relative to the self-help comparison group over time. Changes in social support from friends on social networking websites partially mediated the intervention effects on moderate-to-vigorous PA (mean indirect effect=-22.4; 95% CI: -62.0 to -2.8) in the unexpected direction. Across both groups, social support from friends and self-monitoring were positively associated with changes in moderate-to-vigorous PA. The proposed mediators did not explain the positive effects of the FITNET intervention on mild PA. The lack of significant improvements in psychosocial constructs among FITNET participants may partly explain why the intervention did not increase moderate-to-vigorous PA relative to the self-help comparison group. Future PA interventions with young adult cancer survivors should examine targeting social support from friends and self-monitoring.

Virtual reality for rehabilitation in Parkinson's disease.

PubMed

Dockx, Kim; Bekkers, Esther Mj; Van den Bergh, Veerle; Ginis, Pieter; Rochester, Lynn; Hausdorff, Jeffrey M; Mirelman, Anat; Nieuwboer, Alice

2016-12-21

Parkinson's disease (PD) is a neurodegenerative disorder that is best managed by a combination of medication and regular physiotherapy. In this context, virtual reality (VR) technology is proposed as a new rehabilitation tool with a possible added value over traditional physiotherapy approaches. It potentially optimises motor learning in a safe environment, and by replicating real-life scenarios could help improve functional activities of daily living. The objective of this review was to summarise the current best evidence for the effectiveness of VR interventions for the rehabilitation of people with PD in comparison with 1) active interventions, and 2) passive interventions. Our primary goal was to determine the effect of VR training on gait and balance. Secondary goals included examining the effects of VR on global motor function, activities of daily living, quality of life, cognitive function, exercise adherence, and the occurrence of adverse events. We identified relevant articles through electronic searches of the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), MEDLINE, Embase, CINAHL, the Physiotherapy Evidence Database (PEDro), online trials registers, and by handsearching reference lists. We carried out all searches up until 26 November 2016. We searched for randomised and quasi-randomised controlled trials of VR exercise interventions in people with PD. We included only trials where motor rehabilitation was the primary goal. Two review authors independently searched for trials that corresponded to the predefined inclusion criteria. We independently extracted and assessed all data for methodological quality. A third review author was responsible for conflict resolution when required. We included 8 trials involving 263 people with PD in the review. Risk of bias was unclear or high for all but one of the included studies. Study sample sizes were small, and there was a large amount of heterogeneity between trials with regard to study design and the outcome measures used. As a result, we graded the quality of the evidence as low or very low. Most of the studies intended to improve motor function using commercially available devices, which were compared with physiotherapy. The interventions lasted for between 4 and 12 weeks.In comparison to physiotherapy, VR may lead to a moderate improvement in step and stride length (standardised mean difference (SMD) 0.69, 95% confidence interval (CI) 0.30 to 1.08; 3 studies; 106 participants; low-quality evidence). VR and physiotherapy interventions may have similar effects on gait (SMD 0.20, 95% CI -0.14 to 0.55; 4 studies; 129 participants; low-quality evidence), balance (SMD 0.34, 95% CI -0.04 to 0.71; 5 studies; 155 participants; low-quality evidence), and quality of life (mean difference 3.73 units, 95% CI -2.16 to 9.61; 4 studies; 106 participants). VR interventions did not lead to any reported adverse events, and exercise adherence did not differ between VR and other intervention arms.The evidence available comparing VR exercise with a passive control was more limited. The evidence for the main outcomes of interest was of very low quality due to the very small sample sizes of the two studies available for this comparison. We found low-quality evidence of a positive effect of short-term VR exercise on step and stride length. VR and physiotherapy may have similar effects on gait, balance, and quality of life. The evidence available comparing VR with passive control interventions was more limited. Additional high-quality, large-scale studies are needed to confirm these findings.

Order of stimulus presentation influences children's acquisition in receptive identification tasks.

PubMed

Petursdottir, Anna Ingeborg; Aguilar, Gabriella

2016-03-01

Receptive identification is usually taught in matching-to-sample format, which entails the presentation of an auditory sample stimulus and several visual comparison stimuli in each trial. Conflicting recommendations exist regarding the order of stimulus presentation in matching-to-sample trials. The purpose of this study was to compare acquisition in receptive identification tasks under 2 conditions: when the sample was presented before the comparisons (sample first) and when the comparisons were presented before the sample (comparison first). Participants included 4 typically developing kindergarten-age boys. Stimuli, which included birds and flags, were presented on a computer screen. Acquisition in the 2 conditions was compared in an adapted alternating-treatments design combined with a multiple baseline design across stimulus sets. All participants took fewer trials to meet the mastery criterion in the sample-first condition than in the comparison-first condition. © 2015 Society for the Experimental Analysis of Behavior.

Lack of significant anti-inflammatory activity with clindamycin in the treatment of rosacea: results of 2 randomized, vehicle-controlled trials.

PubMed

Martel, Philippe; Jarratt, Michael; Weiss, Jonathan; Carlavan, Isabelle

2017-07-01

Rosacea is a chronic inflammatory skin disease of the face. The objective of the studies described here was to evaluate the efficacy of clindamycin in the treatment of rosacea. Two multicenter, randomized, vehicle-controlled, phase 2 studies were conducted in participants with moderate to severe rosacea. Study A was a 12-week dose-comparison, 5-arm, parallel group comparison of clindamycin cream 1% or vehicle once or twice daily and clindamycin cream 0.3% once daily. Study B was a 2-arm comparison of twice daily clindamycin gel 1% versus vehicle gel. A total of 629 participants (study A, N=416; study B, N=213) were randomized. The results of these studies indicated that clindamycin cream 0.3% and 1% and clindamycin gel 1% were no more effective than the vehicle in the treatment of moderate to severe rosacea, suggesting clindamycin has no intrinsic anti-inflammatory activity in rosacea.

Effects of a Therapeutic Intervention for Foster Preschoolers on Diurnal Cortisol Activity

PubMed Central

Fisher, Philip A.; Stoolmiller, Mike; Gunnar, Megan R.; Burraston, Bert O.

2007-01-01

Atypical diurnal patterns of hypothalamic-pituitary-adrenal (HPA) axis activity have been observed samples of individuals following early life adversity. A characteristic pattern arising from disrupted caregiving is a low early morning cortisol level that changes little from morning to evening. Less well understood is the plasticity of the HPA axis in response to subsequent supportive caregiving environments. Monthly early morning and evening cortisol levels were assessed over 12 months in a sample of 3- to 6-year-old foster children enrolled in a randomized trial of a family-based therapeutic intervention (N = 117; intervention condition n = 57; regular foster care condition n = 60), and a community comparison group of same-aged, nonmaltreated children from low-income families (n = 60). Latent growth analyses revealed stable and typical diurnal (morning-to-evening) cortisol activity among community comparison children. Foster children in the intervention condition exhibited cortisol activity that became comparable to the comparison group children over the course of the study. In contrast, children in regular foster care condition exhibited increasingly flattened morning-to-evening cortisol activity over the course of the study. In sum, improvements in caregiving following early adversity appear to have the potential to reverse or prevent disruptions in HPA axis functioning. PMID:17656028

SisterTalk: final results of a culturally tailored cable television delivered weight control program for Black women.

PubMed

Risica, Patricia Markham; Gans, Kim M; Kumanyika, Shiriki; Kirtania, Usree; Lasater, Thomas M

2013-12-27

Obesity among Black women continues to exceed that of other women. Most weight loss programs created without reference to specific cultural contexts are less effective for Black than White women. Weight control approaches accessible to Black women and adapted to relevant cultural contexts are important for addressing this problem. This paper reports the final results of SisterTalk, the randomized controlled trial of a cable TV weight control program oriented toward Black women. A five group design included a comparison group and a 2 × 2 factorial comparison of a) interactive vs. passive programming and b) telephone social support vs no telephone support, with 12 weekly initial cable TV programs followed by 4 monthly booster videos. At baseline, 3, 8, and 12 months post randomization, telephone and in person surveys were administered on diet, physical activity, and physical measurements of height and weight were taken to calculate body mass index (BMI). Analysis of variance (ANOVA) was used to examine differences over time, and between treatment and comparison groups. Dose variables reflecting use of the TV/video and written materials were also assessed. At 3 months, BMI, weight, and dietary fat were significantly lower and physical activity significantly higher among women exposed to the Cable TV intervention compared to the wait-list comparison group. Significant dietary fat differences were still observed at 8 and 12 month evaluations, but not BMI or physical activity differences. Main effects were not observed for interactive programming or enhanced social support at any time point. Within the intervention group, higher watching of the TV series and higher reading of educational materials were both (separately) associated with significantly lower dietary fat. Cable TV was an effective delivery channel to assist Black women with weight control, increasing physical activity and decreasing dietary fat during an initial intervention period, but only dietary changes persisted Enhanced social support and the ability to interact with others during the show were not effective complementary intervention components as conducted in this trial. Future research to strengthen the ability of this approach to achieve long term effects may offer even more promising outcomes.

GRIN: "GRoup versus INdividual physiotherapy following lower limb intra-muscular Botulinum Toxin-A injections for ambulant children with cerebral palsy: an assessor-masked randomised comparison trial": study protocol.

PubMed

Thomas, Rachel E; Johnston, Leanne M; Boyd, Roslyn N; Sakzewski, Leanne; Kentish, Megan J

2014-02-07

Cerebral palsy is the most common cause of physical disability in childhood. Spasticity is a significant contributor to the secondary impairments impacting functional performance and participation. The most common lower limb spasticity management is focal intramuscular injections of Botulinum Toxin-Type A accompanied by individually-delivered (one on one) physiotherapy rehabilitation. With increasing emphasis on improving goal-directed functional activity and participation within a family-centred framework, it is timely to explore whether physiotherapy provided in a group could achieve comparable outcomes, encouraging providers to offer flexible models of physiotherapy delivery. This study aims to compare individual to group-based physiotherapy following intramuscular Botulinum Toxin-A injections to the lower limbs for ambulant children with cerebral palsy aged four to fourteen years. An assessor-masked, block randomised comparison trial will be conducted with random allocation to either group-based or individual physiotherapy. A sample size of 30 (15 in each study arm) will be recruited. Both groups will receive six hours of direct therapy following Botulinum Toxin-A injections in either an individual or group format with additional home programme activities (three exercises to be performed three times a week). Study groups will be compared at baseline (T1), then at 10 weeks (T2, efficacy) and 26 weeks (T3, retention) post Botulinum Toxin-A injections. Primary outcomes will be caregiver/s perception of and satisfaction with their child's occupational performance goals (Canadian Occupational Performance Measure) and quality of gait (Edinburgh Visual Gait Score) with a range of secondary outcomes across domains of the International Classification of Disability, Functioning and Health. This paper outlines the study protocol including theoretical basis, study hypotheses and outcome measures for this assessor-masked, randomised comparison trial comparing group versus individual models of physiotherapy following intramuscular injections of Botulinum Toxin-A to the lower limbs for ambulant children with cerebral palsy. ACTRN12611000454976.

Adjuvant bisphosphonate treatment for breast cancer: why did something so elegant become so complicated?

PubMed

Clemons, Mark; Russell, Kent; Costa, Luis; Addison, Christina L

2012-07-01

Bisphosphonate therapy has revolutionized the care of patients with metastatic bone disease. With its demonstrated activity and anti-tumour effects in preclinical studies it was natural to transition these agents to testing in the adjuvant setting. Surprisingly, the results of adjuvant breast cancer trials have shown either modest or no benefit or even harm. We sought to explore whether there were specific patient cohorts or treatment strategies that were most likely to benefit from adjuvant bisphosphonate therapy. We compared trial designs, patient characteristics and outcomes from the six published and two presented randomized adjuvant bisphosphonate trials. Differences in trial design and patient populations make direct comparisons complicated. The most efficacious use of adjuvant bisphosphonates appears to be in patients with either biopsy evidence of osseous micrometastases, were post-menopausal or had estrogen receptor-positive tumours. Despite tremendous optimism regarding adjuvant bisphosphonate therapy, results from large trials are conflicting. Further investigation into factors influencing response to bisphosphonate treatment or selection of appropriate sub-groups of patients with desirable response characteristics is warranted.

[Principles of controlled clinical trials].

PubMed

Martini, P

1962-01-01

The recovery of the patient should be facilitated as the result of therapeutic research. The basic rule for every therapeutic-clinical trial mist involve a comparison of therapeutic approaches. In acute conditions, such as acute infectious diseases, infarcts, etc., comparisons should be made between two or more groups: the collective therapeutic comparison = the between patients trial. The formation of groups, to be compared one with the other can be justified only if one is reasonably sure that a pathogenic condition indeed exists. In chronic diseases, which extend essentially unchanged over a lengthy period but are nevertheless reversible, therapeutic comparisons may be made between two or more time intervals within the course of the disease in the same individual. This type of therapeutic trial rests primarily upon a (refined!) type of specious reasoning and secondarily, upon modified statistics: the individual therapeutic comparison = the within patient trial. The collective therapeutic comparison, on the one hand, and the individual therapeutic comparison on the other, overlap somewhat in scope. The immediate therapeutic effect is not always an indication of its true value, which may become evident only upon long-term treatment. The short-term trials of therapeutic regimens in an individual must, therefore, be frequently supplemented by long-term trials which can only be carried out by comparing two groups. For many clinical investigations, therefore, the joint efforts of numerous hospitals are absolutely necessary. The second basic rule of therapeutic research is the elimination of secondary causes. The difficulties introduced by these secondary considerations are far greater in therapeutic trials carried out on ambulatory patients than has been hitherto realized. In order to remove subjective secondary causes, the author demanded, in 1931, the use of hidden or illusory media (placebos, dummies) that is, unconscious causative agents. The double blind procedure is indispensible in all experiments, especially where psychological processes and problems are of foremost importance. Therefore, it is absolutely necessary that convincing tests be finally carried out with the double blind procedure on the one hand, and the simple blind procedure on the other in order to determine the range and limitations of both. Therapeutic research of the future is threatened by the hazard of self-satisfaction which produces a sense of accomplishment merely as the result of obeying formal conditions and of following formal standards of accuracy.

Higher Antioxidant Activity, Total Flavonols, and Specific Quercetin Glucosides in Two Different Onion (Allium cepa L.) Varieties Grown under Organic Production: Results from a 6-Year Field Study.

PubMed

Ren, Feiyue; Reilly, Kim; Kerry, Joseph P; Gaffney, Michael; Hossain, Mohammad; Rai, Dilip K

2017-06-28

We carried out a 6-year study to assess the effect of conventional, organic, and mixed cultivation practices on bioactive compounds (flavonoids, anthocyanins) and antioxidant capacity in onion. Total flavonoids, total anthocyanins, individual flavonols, individual anthocyanins, and antioxidant activity were measured in two varieties ('Hyskin' and 'Red Baron') grown in a long-term split-plot factorial systems comparison trial. This is the first report of repeated measurements of bioactive content over an extensive time period in a single crop type within the same trial. Antioxidant activity (DPPH and FRAP), total flavonol content, and levels of Q 3,4' D and Q 3 G were higher in both varieties under fully organic compared to fully conventional management. Total flavonoids were higher in 'Red Baron' and when onions were grown under organic soil treatment. Differences were primarily due to different soil management practices used in organic agriculture rather than pesticide/ herbicide application.

Strategy over operation: neural activation in subtraction and multiplication during fact retrieval and procedural strategy use in children.

PubMed

Polspoel, Brecht; Peters, Lien; Vandermosten, Maaike; De Smedt, Bert

2017-09-01

Arithmetic development is characterized by strategy shifts between procedural strategy use and fact retrieval. This study is the first to explicitly investigate children's neural activation associated with the use of these different strategies. Participants were 26 typically developing 4th graders (9- to 10-year-olds), who, in a behavioral session, were asked to verbally report on a trial-by-trial basis how they had solved 100 subtraction and multiplication items. These items were subsequently presented during functional magnetic resonance imaging. An event-related design allowed us to analyze the brain responses during retrieval and procedural trials, based on the children's verbal reports. During procedural strategy use, and more specifically for the decomposition of operands strategy, activation increases were observed in the inferior and superior parietal lobes (intraparietal sulci), inferior to superior frontal gyri, bilateral areas in the occipital lobe, and insular cortex. For retrieval, in comparison to procedural strategy use, we observed increased activity in the bilateral angular and supramarginal gyri, left middle to inferior temporal gyrus, right superior temporal gyrus, and superior medial frontal gyrus. No neural differences were found between the two operations under study. These results are the first in children to provide direct evidence for alternate neural activation when different arithmetic strategies are used and further unravel that previously found effects of operation on brain activity reflect differences in arithmetic strategy use. Hum Brain Mapp 38:4657-4670, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Alternatives for discounting in the analysis of noninferiority trials.

PubMed

Snapinn, Steven M

2004-05-01

Determining the efficacy of an experimental therapy relative to placebo on the basis of an active-control noninferiority trial requires reference to historical placebo-controlled trials. The validity of the resulting comparison depends on two key assumptions: assay sensitivity and constancy. Since the truth of these assumptions cannot be verified, it seems logical to raise the standard of evidence required to declare efficacy; this concept is referred to as discounting. It is not often recognized that two common design and analysis approaches, setting a noninferiority margin and requiring preservation of a fraction of the standard therapy's effect, are forms of discounting. The noninferiority margin is a particularly poor approach, since its degree of discounting depends on an irrelevant factor. Preservation of effect is more reasonable, but it addresses only the constancy assumption, not the issue of assay sensitivity. Gaining consensus on the most appropriate approach to the design and analysis of noninferiority trials will require a common understanding of the concept of discounting.

Activated and Micronized Zeolite in the Modulation of Cellular Oxidative Stress in Mexican Smokers: A Randomized Clinical Trial.

PubMed

Atitlán-Gil, Alfonso; Bretón-de la Loza, Martín M; Jiménez-Ortega, José C; Belefant-Miller, Helen; Betanzos-Cabrera, Gabriel

2017-01-01

Activated and micronized zeolites are used as detoxifying agents in humans. Detoxification is attributed to their ability to reduce lipid peroxidation by scavenging free radicals. To evaluate activated and micronized zeolites as modulators of cellular oxidative stress in Mexican smokers without lung diseases. Randomized clinical trial. Subjects were randomly divided into three groups: activated and micronized zeolites, n = 29; vitamin E, an accepted antioxidant, n = 29; and maltodextrin as control, n = 27. Each group received the corresponding supplementation, dissolved in water, once a day for 30 days as follows: activated and micronized zeolites, 5.4 g activated and micronized zeolite; vitamin E, 400 mg D-alpha tocopheryl acetate; and maltodextrin, 250 mg of maltodextrin. The thiobarbituric acid reactive substances assay was used to screen for lipid peroxidation. Catalase activity, plasma antioxidant capacity, and hydrogen peroxide levels were also measured. Results were analyzed by a one-way ANOVA and post hoc test of Bonferroni. Subjects administered activated and micronized zeolites had equivalent antioxidant activities as subjects administered vitamin E. Activated and micronized zeolites may be useful as a modulator of oxidative stress in smokers. However, inclusion of a comparison group of non-smokers would be useful in future studies to assess the degree to which zeolites reverse the oxidant stress.

Internet-based interventions for the secondary prevention of coronary heart disease.

PubMed

Devi, Reena; Singh, Sally J; Powell, John; Fulton, Emily A; Igbinedion, Ewemade; Rees, Karen

2015-12-22

The Internet could provide a means of delivering secondary prevention programmes to people with coronary heart disease (CHD). To determine the effectiveness of Internet-based interventions targeting lifestyle changes and medicines management for the secondary prevention of CHD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, in December 2014. We also searched six other databases in October 2014, and three trials registers in January 2015 together with reference checking and handsearching to identify additional studies. Randomised controlled trials (RCTs) evaluating Internet-delivered secondary prevention interventions aimed at people with CHD. Two review authors independently assessed risk of bias and extracted data according to the Cochrane Handbook for Systematic Reviews of Interventions. We assessed evidence quality using the GRADE approach and presented this in a 'Summary of findings' table. Eighteen trials met our inclusion criteria. Eleven studies are complete (1392 participants), and seven are ongoing. Of the completed studies, seven interventions are broad, targeting the lifestyle management of CHD, and four focused on physical activity promotion. The comparison group in trials was usual care (n = 6), minimal intervention (n = 3), or traditional cardiac rehabilitation (n = 2).We found no effects of Internet-based interventions for all-cause mortality (odds ratio (OR) 0.27, 95% confidence interval (CI) 0.04 to 1.63; participants = 895; studies = 6; low-quality evidence). There was only one case of cardiovascular mortality in a control group (participants = 895; studies = 6). No incidences of non-fatal re-infarction were reported across any of the studies. We found no effects for revascularisation (OR 0.69, 95% CI 0.37 to 1.27; participants = 895; studies = 6; low-quality evidence).We found no effects for total cholesterol (mean difference (MD) 0.00, 95% CI -0.27 to 0.28; participants = 439; studies = 4; low-quality evidence), high-density lipoprotein (HDL) cholesterol (MD 0.01, 95% CI -0.06 to 0.07; participants = 437; studies = 4; low-quality evidence), or triglycerides (MD 0.01, 95% CI -0.17 to 0.19; participants = 439; studies = 4; low-quality evidence). We did not pool the data for low-density lipoprotein (LDL) cholesterol due to considerable heterogeneity. Two out of six trials measuring LDL cholesterol detected favourable intervention effects, and four trials reported no effects. Seven studies measured systolic and diastolic blood pressure; we did not pool the data due to substantial heterogeneity. For systolic blood pressure, two studies showed a reduction with the intervention, but the remaining studies showed no effect. For diastolic blood pressure, two studies showed a reduction with the intervention, one study showed an increase with the intervention, and the remaining four studies showed no effect.Five trials measured health-related quality of life (HRQOL). We could draw no conclusions from one study due to incomplete reporting; one trial reported no effect; two studies reported a short- and medium-term effect respectively; and one study reported both short- and medium-term effects.Five trials assessed dietary outcomes: two reported favourable effects, and three reported no effects. Eight studies assessed physical activity: five of these trials reported no physical activity effects, and three reported effectiveness. Trials are yet to measure the impact of these interventions on compliance with medication.Two studies measured healthcare utilisation: one reported no effects, and the other reported increased usage of healthcare services compared to a control group in the intervention group at nine months' follow-up. Two trials collected cost data: both reported that Internet-delivered interventions are likely to be cost-effective.In terms of the risk of bias, the majority of studies reported appropriate randomisation and appropriate concealment of randomisation processes. A lack of blinding resulted in a risk of performance bias in seven studies, and a risk of detection bias in five trials. Two trials were at risk of attrition bias, and five were at risk for reporting bias. In general, evidence was of low quality due to lack of blinding, loss to follow-up, and uncertainty around the effect size. Few studies measured clinical events, and of those that did, a very small number of events were reported, and therefore no firm conclusions can be made. Similarly, there was no clear evidence of effect for cardiovascular risk factors, although again the number of studies reporting these was small. There was some evidence for beneficial effects on HRQOL, dietary outcomes, and physical activity, although firm conclusions cannot yet be made. The effects on healthcare utilisation and cost-effectiveness are also inconclusive, and trials are yet to measure the impact of Internet interventions on compliance with medication. The comparison groups differed across trials, and there were insufficient studies with usable data for subgroup analyses. We intend to study the intensity of comparison groups in future updates of this review when more evidence is available. The completion of the ongoing trials will add to the evidence base.

A qualitative systematic review of head-to-head randomized controlled trials of oral analgesics in neuropathic pain

PubMed Central

Watson, C Peter N; Gilron, Ian; Sawynok, Jana

2010-01-01

BACKGROUND: Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well-designed head-to-head comparative trials are an effective way to determine the relative efficacy and safety of a new drug. OBJECTIVE: To perform a systematic review of head-to-head RCTs of oral analgesics in NP. METHODS: A systematic review of RCTs involving NP patients was performed, of which head-to-head comparative trials were selected. Reference lists from published systematic reviews were searched. These studies were rated according to the Jadad scale for quality. RESULTS AND CONCLUSIONS: Twenty-seven such trials were identified. Seventeen were comparisons of different analgesics, and 10 were of different drugs within an analgesic class. Important information was obtained about the relative efficacy and safety of drugs in different categories and within a category. Some significant differences between active treatments were reported. Trial inadequacies were identified. More and improved head-to-head RCTs are needed to inform clinical choices. PMID:20577657

Evaluation of cross-connected waveguides as transfer standards of transmission at high millimetre-wave frequencies

NASA Astrophysics Data System (ADS)

Ridler, Nick; Clarke, Roland; Huang, Hui; Zinal, Sherko

2016-08-01

At the present time, transfer and verification standards of transmission coefficient (or, equivalently, transmission loss) are not readily available at high millimetre-wave frequencies (i.e. at frequencies ranging typically from 100 GHz to 300 GHz). In recent years, cross-connected waveguide devices have been proposed to provide calculable standards of transmission loss at these frequencies. This paper investigates the viability of these cross-connected waveguides as transfer standards of transmission for inter-laboratory measurement comparison exercises. This relates to their potential use in activities such as international key comparison exercises and measurement audit programmes. A trial inter-laboratory comparison involving four laboratories using two cross-connected waveguides in the WR-05 waveguide size (covering frequencies from 140 GHz to 220 GHz) is described and includes an analysis of the measurement results obtained during the comparison exercise.

Computer-delivered and web-based interventions to improve depression, anxiety, and psychological well-being of university students: a systematic review and meta-analysis.

PubMed

Davies, E Bethan; Morriss, Richard; Glazebrook, Cris

2014-05-16

Depression and anxiety are common mental health difficulties experienced by university students and can impair academic and social functioning. Students are limited in seeking help from professionals. As university students are highly connected to digital technologies, Web-based and computer-delivered interventions could be used to improve students' mental health. The effectiveness of these intervention types requires investigation to identify whether these are viable prevention strategies for university students. The intent of the study was to systematically review and analyze trials of Web-based and computer-delivered interventions to improve depression, anxiety, psychological distress, and stress in university students. Several databases were searched using keywords relating to higher education students, mental health, and eHealth interventions. The eligibility criteria for studies included in the review were: (1) the study aimed to improve symptoms relating to depression, anxiety, psychological distress, and stress, (2) the study involved computer-delivered or Web-based interventions accessed via computer, laptop, or tablet, (3) the study was a randomized controlled trial, and (4) the study was trialed on higher education students. Trials were reviewed and outcome data analyzed through random effects meta-analyses for each outcome and each type of trial arm comparison. Cochrane Collaboration risk of bias tool was used to assess study quality. A total of 17 trials were identified, in which seven were the same three interventions on separate samples; 14 reported sufficient information for meta-analysis. The majority (n=13) were website-delivered and nine interventions were based on cognitive behavioral therapy (CBT). A total of 1795 participants were randomized and 1480 analyzed. Risk of bias was considered moderate, as many publications did not sufficiently report their methods and seven explicitly conducted completers' analyses. In comparison to the inactive control, sensitivity meta-analyses supported intervention in improving anxiety (pooled standardized mean difference [SMD] -0.56; 95% CI -0.77 to -0.35, P<.001), depression (pooled SMD -0.43; 95% CI -0.63 to -0.22, P<.001), and stress (pooled SMD -0.73; 95% CI -1.27 to -0.19, P=.008). In comparison to active controls, sensitivity analyses did not support either condition for anxiety (pooled SMD -0.18; 95% CI -0.98 to 0.62, P=.66) or depression (pooled SMD -0.28; 95% CI -0.75 to -0.20, P=.25). In contrast to a comparison intervention, neither condition was supported in sensitivity analyses for anxiety (pooled SMD -0.10; 95% CI -0.39 to 0.18, P=.48) or depression (pooled SMD -0.33; 95% CI -0.43 to 1.09, P=.40). The findings suggest Web-based and computer-delivered interventions can be effective in improving students' depression, anxiety, and stress outcomes when compared to inactive controls, but some caution is needed when compared to other trial arms and methodological issues were noticeable. Interventions need to be trialed on more heterogeneous student samples and would benefit from user evaluation. Future trials should address methodological considerations to improve reporting of trial quality and address post-intervention skewed data.

Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial

PubMed Central

Scriven, James E.; Rhein, Joshua; Hullsiek, Katherine Huppler; von Hohenberg, Maximilian; Linder, Grace; Rolfes, Melissa A.; Williams, Darlisha A.; Taseera, Kabanda; Meya, David B.; Meintjes, Graeme; Boulware, David R.

2015-01-01

Introduction. Earlier antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality compared with deferred ART initiation (1–2 weeks vs 5 weeks postmeningitis diagnosis). We hypothesized this was due to ART-associated immune pathology, without clinically recognized immune reconstitution inflammatory syndrome. Methods. Three macrophage activation markers and 19 cytokines/chemokines were measured from cryopreserved cerebrospinal fluid (CSF) and serum during the Cryptococcal Optimal ART Timing (COAT) trial. Comparisons were made between trial arms (early vs deferred) at 1, 8, 14, and 21 days following meningitis diagnosis. Results. More participants with early ART initiation had CSF white cell count (WCC) ≥5/µL at day 14 (58% vs 40%; P = .047), after a median of 6-days ART. Differences were mainly driven by participants with CSF WCC <5/µL at meningitis diagnosis: 28% (10/36) of such persons in the early ART group had CSF WCC ≥5/µL by day 14, compared with 0% (0/27) in the deferred arm (P = .002). Furthermore, Kampala participants (the largest site) receiving early ART had higher day-14 CSF levels of interleukin-13 (P = .04), sCD14 (P = .04), sCD163 (P = .02), and CCL3/MIP-1α (P = .02), suggesting increased macrophage/microglial activation. Conclusions. Early ART initiation in cryptococcal meningitis increased CSF cellular infiltrate, macrophage/microglial activation, and T helper 2 responses within the central nervous system. This suggests that increased mortality from early ART in the COAT trial was immunologically mediated. PMID:25651842

Comparative effects of meditation and exercise on physical and psychosocial health outcomes: a review of randomized controlled trials.

PubMed

Edwards, Meghan K; Loprinzi, Paul D

2018-03-01

No review papers have examined studies that have directly compared non-active forms of meditation with exercise to evaluate effects on physical or psychosocial outcomes, which was the purpose of this paper. Studies were included if they had a randomized controlled trial (RCT) design, included a non-active form of meditation and exercise as intervention arms, and evaluated physical or psychosocial outcomes. The quality of included RCTs was rated using the Cochrane Collaboration's tool for assessing risk of bias in randomized trials. Five RCTs met the inclusion criteria. The total sample size across all studies was N = 325. Of the main outcomes assessed across the five studies, meditation was shown to be more effective than the exercise comparison arm when evaluating the psychosocial outcomes of anxiety, altruism, and life changes. Additionally, meditation was more effective at reducing chronic neck pain at rest and pain-related bothersomeness. Exercise, however, was more effective in improving physical health-related quality of life, HDL and LDL cholesterol, and fasting blood glucose levels. The interventions were found to be comparable when evaluating the outcomes of well-being, ethanol consumption, and perceived stress levels. Four of the evaluated studies were determined to have an overall 'unclear' risk of bias and one study was found to have a 'high' risk of bias. Exercise and non-active meditation may uniquely influence various health-related outcomes. A continued exploration of the effects of exercise and non-active meditation in controlled trials may yield a better understanding of their benefits.

Antiepileptic drugs as prophylaxis for postcraniotomy seizures.

PubMed

Greenhalgh, Janette; Weston, Jennifer; Dundar, Yenal; Nevitt, Sarah J; Marson, Anthony G

2018-05-23

This is an updated version of the Cochrane Review previously published in Issue 3, 2015.The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs). To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective. For the latest update we searched the following databases on 26 June 2017: Cochrane Epilepsy Group Specialized Register, the CENTRAL, MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We did not apply any language restrictions. We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. We included trials with adequate randomisation methods and concealment; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group. Three review authors (JW, JG, YD) independently selected trials for inclusion and performed data extraction and risk of bias assessments. We resolved any disagreements through discussion. Outcomes investigated included the number of participants experiencing seizures (early (occurring within first week following craniotomy), and late (occurring after first week following craniotomy)), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a meta-analysis; we presented the findings of the review in narrative format. Visual comparisons of outcomes are presented in forest plots. We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence.Incidences of death were reported in only five trials. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability.We considered the evidence to be of low quality for all reported outcomes due to methodological issues and variability of comparisons made in the trials. There is limited, low-quality evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.

Comparison of propranolol and practolol in the management of hyperthyroidism.

PubMed

Murchison, L E; Bewsher, P D; Chesters, M I; Ferrier, W R

1976-04-01

Twenty-one hyperthyroid patients participated in an 8-week double-blind crossover trial of propranolol and practolol, and the effecte of these drugs on the clinical and metabolic features of the disease were studied. Propranolol was marginally more effective than practolol, as measured by the hyperthyroid diagnostic index and anxiety scale. Propranolol produced a significant reduction in the serum concentration ratio of tri-iodothyronine to thyroxine, compatible with partial inhibition of peripheral deiodination of thyroxine. Adverse reactions occurred more frequently with propranolol than with practolol. In veiw of the efficacy of practoloo, further trials in hyperthyroid patients of newer beta1-adrenoceptor antagonists, preferably without partial agonist activity, are indicated.

Impact of fingolimod therapy on magnetic resonance imaging outcomes in patients with multiple sclerosis.

PubMed

Radue, Ernst-Wilhelm; O'Connor, Paul; Polman, Chris H; Hohlfeld, Reinhard; Calabresi, Peter; Selmaj, Krystof; Mueller-Lenke, Nicole; Agoropoulou, Catherine; Holdbrook, Frederick; de Vera, Ana; Zhang-Auberson, Lixin; Francis, Gordon; Burtin, Pascale; Kappos, Ludwig

2012-10-01

To assess the impact of fingolimod (FTY720) therapy on magnetic resonance imaging measures of inflammatory activity and tissue damage in patients participating in a 2-year, placebo-controlled, phase 3 study. Patients with active relapsing-remitting multiple sclerosis were randomized to receive fingolimod, 0.5 mg; fingolimod, 1.25 mg; or placebo for 2 years. Standardized magnetic resonance imaging scans were obtained at months 0, 6, 12, and 24 and centrally evaluated for number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions and for percentage of brain volume change. Findings were compared across subgroups by treatment and baseline characteristics. Worldwide, multicenter clinical trial. Patients were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial for relapsing-remitting multiple sclerosis (N=1272). We measured the effect of therapy on acute inflammatory activity, burden of disease, and irreversible loss of brain volume. Fingolimod therapy resulted in rapid and sustained reductions in inflammatory lesion activity as assessed by gadolinium-enhancing and new/newly enlarged T2 lesions after 6, 12, and 24 months of therapy (P.001, all comparisons vs placebo). Changes in T2 hyperintense and T1 hypointense lesion volume also significantly favored fingolimod (P.05, all comparisons). Fingolimod, 0.5 mg (licensed dose), significantly reduced brain volume loss during months 0 to 6, 0 to 12, 12 to 24, and 0 to 24 (P.05, all comparisons) vs placebo, and subgroup analyses confirmed these effects over 2 years irrespective of the presence/absence of gadolinium-enhancing lesions, T2 lesion load, previous treatment status, or level of disability. These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution. clinicaltrials.gov Identifier: NCT00289978

Reporting of analyses from randomized controlled trials with multiple arms: a systematic review.

PubMed

Baron, Gabriel; Perrodeau, Elodie; Boutron, Isabelle; Ravaud, Philippe

2013-03-27

Multiple-arm randomized trials can be more complex in their design, data analysis, and result reporting than two-arm trials. We conducted a systematic review to assess the reporting of analyses in reports of randomized controlled trials (RCTs) with multiple arms. The literature in the MEDLINE database was searched for reports of RCTs with multiple arms published in 2009 in the core clinical journals. Two reviewers extracted data using a standardized extraction form. In total, 298 reports were identified. Descriptions of the baseline characteristics and outcomes per group were missing in 45 reports (15.1%) and 48 reports (16.1%), respectively. More than half of the articles (n = 171, 57.4%) reported that a planned global test comparison was used (that is, assessment of the global differences between all groups), but 67 (39.2%) of these 171 articles did not report details of the planned analysis. Of the 116 articles reporting a global comparison test, 12 (10.3%) did not report the analysis as planned. In all, 60% of publications (n = 180) described planned pairwise test comparisons (that is, assessment of the difference between two groups), but 20 of these 180 articles (11.1%) did not report the pairwise test comparisons. Of the 204 articles reporting pairwise test comparisons, the comparisons were not planned for 44 (21.6%) of them. Less than half the reports (n = 137; 46%) provided baseline and outcome data per arm and reported the analysis as planned. Our findings highlight discrepancies between the planning and reporting of analyses in reports of multiple-arm trials.

Comparison of Compliance and Intervention Outcomes Between Hip- and Wrist-Worn Accelerometers During a Randomized Crossover Trial of an Active Video Games Intervention in Children.

PubMed

Howie, Erin K; McVeigh, Joanne A; Straker, Leon M

2016-09-01

There are several practical issues when considering the use of hip-worn or wrist-worn accelerometers. This study compared compliance and outcomes between hip- and wrist-worn accelerometers worn simultaneously by children during an active video games intervention. As part of a larger randomized crossover trial, participants (n = 73, age 10 to 12 years) wore 2 Actical accelerometers simultaneously during waking hours for 7 days, on the hip and wrist. Measurements were repeated at 4 timepoints: 1) at baseline, 2) during traditional video games condition, 3) during active video games condition, 4) during no video games condition. Compliance and intervention effects were compared between hip and wrist. There were no statistically significant differences at any timepoint in percentage compliance between hip (77% to 87%) and wrist (79% to 89%). Wrist-measured counts (difference of 64.3 counts per minute, 95% CI 4.4-124.3) and moderate-to-vigorous physical activity (MVPA) (12 min/day, 95% CI 0.3-23.7) were higher during the no video games condition compared with the traditional video games condition. There were no differences in hip-measured counts per minute or MVPA between conditions or sedentary time for hip or wrist. There were no differences in compliance between hip- and wrist-worn accelerometers during an intervention trial, however, intervention findings differed between hip and wrist.

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.

Exposure to a multi-level multi-component childhood obesity prevention community-randomized controlled trial: patterns, determinants, and implications.

PubMed

Trude, Angela Cristina Bizzotto; Kharmats, Anna Yevgenyevna; Jones-Smith, Jessica C; Gittelsohn, Joel

2018-05-22

For community interventions to be effective in real-world conditions, participants need to have sufficient exposure to the intervention. It is unclear how the dose and intensity of the intervention differ among study participants in low-income areas. We aimed to understand patterns of exposure to different components of a multi-level multi-component obesity prevention program to inform our future impact analyses. B'more Healthy Communities for Kids (BHCK) was a community-randomized controlled trial implemented in 28 low-income zones in Baltimore in two rounds (waves). Exposure to three different intervention components (corner store/carryout restaurants, social media/text messaging, and youth-led nutrition education) was assessed via post-intervention interviews with 385 low-income urban youths and their caregivers. Exposure scores were generated based on self-reported viewing of BHCK materials (posters, handouts, educational displays, and social media posts) and participating in activities, including taste tests during the intervention. For each intervention component, points were assigned for exposure to study materials and activities, then scaled (0-1 range), yielding an overall BHCK exposure score [youths: mean 1.1 (range 0-7.6 points); caregivers: 1.1 (0-6.7), possible highest score: 13]. Ordered logit regression analyses were used to investigate correlates of youths' and caregivers' exposure level (quartile of exposure). Mean intervention exposure scores were significantly higher for intervention than comparison youths (mean 1.6 vs 0.5, p < 0.001) and caregivers (mean 1.6 vs 0.6, p < 0.001). However, exposure scores were low in both groups and 10% of the comparison group was moderately exposed to the intervention. For each 1-year increase in age, there was a 33% lower odds of being highly exposed to the intervention (odds ratio 0.77, 95% confidence interval 0.69; 0.88) in the unadjusted and adjusted model controlling for youths' sex and household income. Treatment effects may be attenuated in community-based trials, as participants may be differentially exposed to intervention components and the comparison group may also be exposed. Exposure should be measured to provide context to impact evaluations in multi-level trials. Future analyses linking exposure scores to the outcome should control for potential confounders in the treatment-on-the-treated approach, while recognizing that confounding and selection bias may exist affecting causal inference. ClinicalTrials.gov, NCT02181010 . Retrospectively registered on 2 July 2014.

Activation Pattern of Lower Leg Muscles in Running on Asphalt, Gravel and Grass.

PubMed

Dolenec, Aleš; Štirn, Igor; Strojnik, Vojko

2015-07-01

Running is performed on different natural surfaces (outdoor) and artificial surfaces (indoor). Different surface characteristics cause modification of the lower leg muscle activation pattern to adopt ankle stiffness to these characteristics. So the purpose of our investigation was to study changes of lower leg muscles activation pattern in running on different natural running surfaces. Six male and two female runners participated. The participants ran at a freely chosen velocity in trials on asphalt while in trials on gravel, and grass surfaces they were attempting to reach similar velocities as in the trials on asphalt. Muscle activation of the peroneus brevis, tibialis anterior, soleus, and gastrocnemius medialis of the right leg was recorded. Running on asphalt increased average EMG amplitude of the m. tibialis anterior in the pre-activation phase and the m. gastrocnemius medialis in the entire contact phase compared to running on grass from 0.222 ± 0.113 V to 0.276 ± 0.136 V and from 0.214 ± 0.084 V to 0.238 ± 0.088 V, respectively. The average EMG of m. peroneus brevis in pre-activation phase increased from 0.156 ± 0.026 V to 0.184 ± 0.455 V in running on grass in comparison to running on gravel. Running on different surfaces is connected with different activation patterns of lower leg muscles. Running on asphalt requires stiff ankle joints, running on gravel requires greater stability in ankle joints, while running on grass is the least demanding on lower leg muscles.

Skylab task and work performance /Experiment M-151 - Time and motion study/

NASA Technical Reports Server (NTRS)

Kubis, J. F.; Mclaughlin, E. J.

1975-01-01

The primary objective of Experiment M151 was to study the inflight adaptation of Skylab crewmen to a variety of task situations involving different types of activity. A parallel objective was to examine astronaut inflight performance for any behavioral stress effects associated with the working and living conditions of the Skylab environment. Training data provided the basis for comparison of preflight and inflight performance. Efficiency was evaluated through the adaptation function, namely, the relation of performance time over task trials. The results indicate that the initial changeover from preflight to inflight was accompanied by a substantial increase in performance time for most work and task activities. Equally important was the finding that crewmen adjusted rapidly to the weightless environment and became proficient in developing techniques with which to optimize task performance. By the end of the second inflight trial, most of the activities were performed almost as efficiently as on the last preflight trial. The analysis demonstrated the sensitivity of the adaptation function to differences in task and hardware configurations. The function was found to be more regular and less variable inflight than preflight. Translation and control of masses were accomplished easily and efficiently through the rapid development of the arms and legs as subtle guidance and restraint systems.

Maintenance of Blinding in Clinical Trials and the Implications for Studying Analgesia Using Cannabinoids

PubMed Central

Wilsey, Barth; Deutsch, Reena; Marcotte, Thomas D.

2016-01-01

Abstract The design of analgesic clinical trials invariably involves a comparison between placebo and active study medication. An assumption is made that treatment effects can be approximated by subtracting the response to placebo from that attained with the use of active study medication. However, the psychoactivity of cannabinoids may unmask their presence and lead to an expectation and/or conditioning of pain relief. For example, study participants biased toward the belief that cannabis is beneficial for their condition might be more inclined to report positive effects if they were to accurately identify the active treatment because of its psychoactivity. This may lead to incorrect assumptions regarding the efficacy of a cannabinoid. Methodologies designed to counteract unmasking need to be implemented in the design phase of a study. During the clinical trial, it is also important to query participants as to which treatment they believe they have received. Blinding can be considered to be preserved when the accuracy of treatment guesses is not considerably different than random guessing, which is estimated to be correct 50% of the time. After a study has been completed, the use of statistical methodologies such as regression and mediation analysis are worthy of consideration to see whether psychoactive effects biased the results. PMID:28861490

Acupuncture for peripheral joint osteoarthritis

PubMed Central

Manheimer, Eric; Cheng, Ke; Linde, Klaus; Lao, Lixing; Yoo, Junghee; Wieland, Susan; van der Windt, Daniëlle AWM; Berman, Brian M; Bouter, Lex M

2011-01-01

Background Peripheral joint osteoarthritis is a major cause of pain and functional limitation. Few treatments are safe and effective. Objectives To assess the effects of acupuncture for treating peripheral joint osteoarthritis. Search strategy We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 1), MEDLINE, and EMBASE (both through December 2007), and scanned reference lists of articles. Selection criteria Randomized controlled trials (RCTs) comparing needle acupuncture with a sham, another active treatment, or a waiting list control group in people with osteoarthritis of the knee, hip, or hand. Data collection and analysis Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We calculated standardized mean differences using the differences in improvements between groups. Main results Sixteen trials involving 3498 people were included. Twelve of the RCTs included only people with OA of the knee, 3 only OA of the hip, and 1 a mix of people with OA of the hip and/or knee. In comparison with a sham control, acupuncture showed statistically significant, short-term improvements in osteoarthritis pain (standardized mean difference -0.28, 95% confidence interval -0.45 to -0.11; 0.9 point greater improvement than sham on 20 point scale; absolute percent change 4.59%; relative percent change 10.32%; 9 trials; 1835 participants) and function (-0.28, -0.46 to -0.09; 2.7 point greater improvement on 68 point scale; absolute percent change 3.97%; relative percent change 8.63%); however, these pooled short-term benefits did not meet our predefined thresholds for clinical relevance (i.e. 1.3 points for pain; 3.57 points for function) and there was substantial statistical heterogeneity. Additionally, restriction to sham-controlled trials using shams judged most likely to adequately blind participants to treatment assignment (which were also the same shams judged most likely to have physiological activity), reduced heterogeneity and resulted in pooled short-term benefits of acupuncture that were smaller and non-significant. In comparison with sham acupuncture at the six-month follow-up, acupuncture showed borderline statistically significant, clinically irrelevant improvements in osteoarthritis pain (-0.10, -0.21 to 0.01; 0.4 point greater improvement than sham on 20 point scale; absolute percent change 1.81%; relative percent change 4.06%; 4 trials;1399 participants) and function (-0.11, -0.22 to 0.00; 1.2 point greater improvement than sham on 68 point scale; absolute percent change 1.79%; relative percent change 3.89%). In a secondary analysis versus a waiting list control, acupuncture was associated with statistically significant, clinically relevant short-term improvements in osteoarthritis pain (-0.96, -1.19 to -0.72; 14.5 point greater improvement than sham on 100 point scale; absolute percent change 14.5%; relative percent change 29.14%; 4 trials; 884 participants) and function (-0.89, -1.18 to -0.60; 13.0 point greater improvement than sham on 100 point scale; absolute percent change 13.0%; relative percent change 25.21%). In the head-on comparisons of acupuncture with the ‘supervised osteoarthritis education’ and the ‘physician consultation’ control groups, acupuncture was associated with clinically relevant short- and long-term improvements in pain and function. In the head on comparisons of acupuncture with ‘home exercises/advice leaflet’ and ‘supervised exercise’, acupuncture was associated with similar treatment effects as the controls. Acupuncture as an adjuvant to an exercise based physiotherapy program did not result in any greater improvements than the exercise program alone. Information on safety was reported in only 8 trials and even in these trials there was limited reporting and heterogeneous methods. Authors' conclusions Sham-controlled trials show statistically significant benefits; however, these benefits are small, do not meet our pre-defined thresholds for clinical relevance, and are probably due at least partially to placebo effects from incomplete blinding. Waiting list-controlled trials of acupuncture for peripheral joint osteoarthritis suggest statistically significant and clinically relevant benefits, much of which may be due to expectation or placebo effects. PMID:20091527

Breast cancer risk reduction--is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

PubMed

Anderson, Annie S; Macleod, Maureen; Mutrie, Nanette; Sugden, Jacqueline; Dobson, Hilary; Treweek, Shaun; O'Carroll, Ronan E; Thompson, Alistair; Kirk, Alison; Brennan, Graham; Wyke, Sally

2014-12-17

Breast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reduction. This study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP). A 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity). At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women's, coaches, and radiographers' experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effect. A pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58 ± 5.6 years, mean BMI was 29.2 ± 7.0 kg/m(2) and many (44%) reported a family history of breast cancer. The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95% CI -3.24 kg to -0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others. Recruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects. The trial was registered with Current Controlled Trials (ISRCTN56223933).

Strategy Use and Strategy Choice in Fraction Magnitude Comparison

ERIC Educational Resources Information Center

Fazio, Lisa K.; DeWolf, Melissa; Siegler, Robert S.

2016-01-01

We examined, on a trial-by-trial basis, fraction magnitude comparison strategies of adults with more and less mathematical knowledge. College students with high mathematical proficiency used a large variety of strategies that were well tailored to the characteristics of the problems and that were guaranteed to yield correct performance if executed…

Two-digit number comparison: Decade-unit and unit-decade produce the same compatibility effect with number words.

PubMed

Macizo, Pedro; Herrera, Amparo

2010-03-01

This study explored the processing of 2-digit number words by examining the unit-decade compatibility effect in Spanish. Participants were required to choose the larger of 2-digit number words presented in verbal notation. In compatible trials the decade and unit comparisons led to the same response (e.g., 53-68) while in incompatible trials the decade and unit comparisons led to different responses (e.g., 59-74). Participants were slower on compatible trials as compared to incompatible trials. In Experiments 2 and 3, we evaluated whether the reverse compatibility effect in Spanish was only due to a pure left-to-right encoding which favours the decade processing in this language (decade-unit order). When participants processed 2-digit number words presented in reverse form (in the unit-decade order), the same reverse compatibility effect was found. This pattern of results suggests that participants have learnt a language-dependent process for analysing written numbers which is used irrespective of the specific arrangement of units and decades in the comparison task. 2010 APA, all rights reserved.

Neural correlates of the spatial and expectancy components of endogenous and stimulus-driven orienting of attention in the Posner task.

PubMed

Doricchi, Fabrizio; Macci, Enrica; Silvetti, Massimo; Macaluso, Emiliano

2010-07-01

Voluntary orienting of visual attention is conventionally measured in tasks with predictive central cues followed by frequent valid targets at the cued location and by infrequent invalid targets at the uncued location. This implies that invalid targets entail both spatial reorienting of attention and breaching of the expected spatial congruency between cues and targets. Here, we used event-related functional magnetic resonance imaging (fMRI) to separate the neural correlates of the spatial and expectancy components of both endogenous orienting and stimulus-driven reorienting of attention. We found that during endogenous orienting with predictive cues, there was a significant deactivation of the right Temporal-Parietal Junction (TPJ). We also discovered that the lack of an equivalent deactivation with nonpredictive cues was matched to drop in attentional costs and preservation of attentional benefits. The right TPJ showed equivalent responses to invalid targets following predictive and nonpredictive cues. On the contrary, infrequent-unexpected invalid targets following predictive cues specifically activated the right Middle and Inferior Frontal Gyrus (MFG-IFG). Additional comparisons with spatially neutral trials demonstrated that, independently of cue predictiveness, valid targets activate the left TPJ, whereas invalid targets activate both the left and right TPJs. These findings show that the selective right TPJ activation that is found in the comparison between invalid and valid trials results from the reciprocal cancelling of the different activations that in the left TPJ are related to the processing of valid and invalid targets. We propose that left and right TPJs provide "matching and mismatching to attentional template" signals. These signals enable reorienting of attention and play a crucial role in the updating of the statistical contingency between cues and targets.

Comparison of glomerular activity patterns by fMRI and wide-field calcium imaging: implications for principles underlying odor mapping

PubMed Central

Sanganahalli, Basavaraju G.; Rebello, Michelle R.; Herman, Peter; Papademetris, Xenophon; Shepherd, Gordon M.; Verhagen, Justus V.; Hyder, Fahmeed

2015-01-01

Functional imaging signals arise from distinct metabolic and hemodynamic events at the neuropil, but how these processes are influenced by pre- and post-synaptic activities need to be understood for quantitative interpretation of stimulus-evoked mapping data. The olfactory bulb (OB) glomeruli, spherical neuropil regions with well-defined neuronal circuitry, can provide insights into this issue. Optical calcium-sensitive fluorescent dye imaging (OICa2+) reflects dynamics of pre-synaptic input to glomeruli, whereas high-resolution functional magnetic resonance imaging (fMRI) using deoxyhemoglobin contrast reveals neuropil function within the glomerular layer where both pre- and post-synaptic activities contribute. We imaged odor-specific activity patterns of the dorsal OB in the same anesthetized rats with fMRI and OICa2+ and then co-registered the respective maps to compare patterns in the same space. Maps by each modality were very reproducible as trial-to-trial patterns for a given odor, overlapping by ~80%. Maps evoked by ethyl butyrate and methyl valerate for a given modality overlapped by ~80%, suggesting activation of similar dorsal glomerular networks by these odors. Comparison of maps generated by both methods for a given odor showed ~70% overlap, indicating similar odor-specific maps by each method. These results suggest that odor-specific glomerular patterns by high-resolution fMRI primarily tracks pre-synaptic input to the OB. Thus combining OICa2+ and fMRI lays the framework for studies of OB processing over a range of spatiotemporal scales, where OICa2+ can feature the fast dynamics of dorsal glomerular clusters and fMRI can map the entire glomerular sheet in the OB. PMID:26631819

Effects of massage therapy and occlusal splint therapy on mandibular range of motion in individuals with temporomandibular disorder: a randomized clinical trial.

PubMed

Gomes, Cid André Fidelis de Paula; Politti, Fabiano; Andrade, Daniel Ventura; de Sousa, Dowglas Fernando Magalhães; Herpich, Carolina Marciela; Dibai-Filho, Almir Vieira; Gonzalez, Tabajara de Oliveira; Biasotto-Gonzalez, Daniela Aparecida

2014-01-01

The purpose of this study was to investigate the effects of massage therapy compared with occlusal splint therapy on mandibular range of motion (ROM) in individuals with temporomandibular disorder (TMD) and compare the results with ROM obtained in a group of individuals without this disorder. A blinded randomized clinical trial was conducted. Twenty-eight volunteers with TMD were randomly distributed into either a massage therapy group or an occlusal splint group. Both treatments were provided for 4 weeks. Fourteen individuals without TMD were consecutively allocated to a comparison group. Fonseca anamnestic index was used to characterize TMD and allocate the volunteers to either of the intervention groups or asymptomatic comparison group. Mandibular ROM was evaluated before and after treatment using a digital caliper. Two-way repeated-measures analysis of variance with a post hoc Bonferroni testing was used for intergroup and intragroup comparisons (level of significance was set to 5%). Cohen d was used to calculate the effect size. In the intragroup analysis, significant increases in ROM were found for all measures in both the massage and occlusal splint groups (P < .05). A small to moderate clinical effect of treatment with the occlusal splint was found regarding right and left lateral excursion in comparison with the massage therapy and asymptomatic comparison groups (0.2

Comparison of different spatial transformations applied to EEG data: A case study of error processing.

PubMed

Cohen, Michael X

2015-09-01

The purpose of this paper is to compare the effects of different spatial transformations applied to the same scalp-recorded EEG data. The spatial transformations applied are two referencing schemes (average and linked earlobes), the surface Laplacian, and beamforming (a distributed source localization procedure). EEG data were collected during a speeded reaction time task that provided a comparison of activity between error vs. correct responses. Analyses focused on time-frequency power, frequency band-specific inter-electrode connectivity, and within-subject cross-trial correlations between EEG activity and reaction time. Time-frequency power analyses showed similar patterns of midfrontal delta-theta power for errors compared to correct responses across all spatial transformations. Beamforming additionally revealed error-related anterior and lateral prefrontal beta-band activity. Within-subject brain-behavior correlations showed similar patterns of results across the spatial transformations, with the correlations being the weakest after beamforming. The most striking difference among the spatial transformations was seen in connectivity analyses: linked earlobe reference produced weak inter-site connectivity that was attributable to volume conduction (zero phase lag), while the average reference and Laplacian produced more interpretable connectivity results. Beamforming did not reveal any significant condition modulations of connectivity. Overall, these analyses show that some findings are robust to spatial transformations, while other findings, particularly those involving cross-trial analyses or connectivity, are more sensitive and may depend on the use of appropriate spatial transformations. Copyright © 2014 Elsevier B.V. All rights reserved.

Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

PubMed Central

McMurray, John J. V.; Packer, Milton; Desai, Akshay S.; Gong, Jim; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.

2013-01-01

Aims Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin–angiotensin–aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides. Methods Patients with chronic HF, NYHA class II–IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death. Perspectives PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF. Trial registration NCT01035255 PMID:23563576

Economic Evaluations of Pharmaceuticals Granted a Marketing Authorisation Without the Results of Randomised Trials: A Systematic Review and Taxonomy.

PubMed

Hatswell, Anthony J; Freemantle, Nick; Baio, Gianluca

2017-02-01

Pharmaceuticals are usually granted a marketing authorisation on the basis of randomised controlled trials (RCTs). Occasionally the efficacy of a treatment is assessed without a randomised comparator group (either active or placebo). To identify and develop a taxonomic account of economic modelling approaches for pharmaceuticals licensed without RCT data. We searched PubMed, the websites of UK health technology assessment bodies and the International Society for Pharmacoeconomics and Outcomes Research Scientific Presentations Database for assessments of treatments granted a marketing authorisation by the US Food and Drug Administration or European Medicines Agency from January 1999 to May 2014 without RCT data (74 indications). The outcome of interest was the approach to modelling efficacy data. Fifty-one unique models were identified in 29 peer-reviewed articles, 30 health technology appraisals, and 15 International Society for Pharmacoeconomics and Outcomes Research abstracts concerning 30 indications (44 indications had not been modelled). We noted the high rate of non-submission to health technology assessment agencies (28/98). The majority of models (43/51) were based on 'historical controls'-comparisons to previous meta-analysis or pooling of trials (5), individual trials (16), registries/case series (15), or expert opinion (7). Other approaches used the patient as their own control, performed threshold analysis, assumed time on treatment was added to overall survival, or performed cost-minimisation analysis. There is considerable variation in the quality and approach of models constructed for drugs granted a marketing authorisation without a RCT. The most common approach is of a naive comparison to historical data (using other trials/registry data as a control group), which has considerable scope for bias.

A multi-level intervention in worksites to increase fruit and vegetable access and intake: Rationale, design and methods of the 'Good to Go' cluster randomized trial.

PubMed

Risica, Patricia M; Gorham, Gemma; Dionne, Laura; Nardi, William; Ng, Doug; Middler, Reese; Mello, Jennifer; Akpolat, Rahmet; Gettens, Katelyn; Gans, Kim M

2018-02-01

Fruit and vegetable (F&V) consumption is an important contributor to chronic disease prevention. However, most Americans do not eat adequate amounts. The worksite is an advantageous setting to reach large, diverse segments of the population with interventions to increase F&V intake, but research gaps exist. No studies have evaluated the implementation of mobile F&V markets at worksites nor compared the effectiveness of such markets with or without nutrition education. This paper describes the protocol for Good to Go (GTG), a cluster randomized trial to evaluate F&V intake change in employees from worksites randomized into three experimental arms: discount, fresh F&V markets (Access Only arm); markets plus educational components including campaigns, cooking demonstrations, videos, newsletters, and a web site (Access Plus arm); and an attention placebo comparison intervention on physical activity and stress reduction (Comparison). Secondary aims include: 1) Process evaluation to determine costs, reach, fidelity, and dose as well as the relationship of these variables with changes in F&V intake; 2) Applying a mediating variable framework to examine relationships of psychosocial factors/determinants with changes in F&V consumption; and 3) Cost effectiveness analysis of the different intervention arms. The GTG study will fill important research gaps in the field by implementing a rigorous cluster randomized trial to evaluate the efficacy of an innovative environmental intervention providing access and availability to F&V at the worksite and whether this access intervention is further enhanced by accompanying educational interventions. GTG will provide an important contribution to public health research and practice. Trial registration number NCT02729675, ClinicalTrials.gov. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A multi-level intervention in worksites to increase fruit and vegetable access and intake: Rationale, design and methods of the ‘Good to Go’ cluster randomized trial

PubMed Central

Risica, Patricia M.; Gorham, Gemma; Dionne, Laura; Nardi, William; Ng, Doug; Middler, Reese; Mello, Jennifer; Akpolat, Rahmet; Gettens, Katelyn; Gans, Kim M.

2018-01-01

Background Fruit and vegetable (F&V) consumption is an important contributor to chronic disease prevention. However, most Americans do not eat adequate amounts. The worksite is an advantageous setting to reach large, diverse segments of the population with interventions to increase F&V intake, but research gaps exist. No studies have evaluated the implementation of mobile F&V markets at worksites nor compared the effectiveness of such markets with or without nutrition education. Methods This paper describes the protocol for Good to Go (GTG), a cluster randomized trial to evaluate F&V intake change in employees from worksites randomized into three experimental arms: discount, fresh F&V markets (Access Only arm); markets plus educational components including campaigns, cooking demonstrations, videos, newsletters, and a web site (Access Plus arm); and an attention placebo comparison intervention on physical activity and stress reduction (Comparison). Secondary aims include: 1) Process evaluation to determine costs, reach, fidelity, and dose as well as the relationship of these variables with changes in F&V intake; 2) Applying a mediating variable framework to examine relationships of psychosocial factors/determinants with changes in F&V consumption; and 3) Cost effectiveness analysis of the different intervention arms. Discussion The GTG study will fill important research gaps in the field by implementing a rigorous cluster randomized trial to evaluate the efficacy of an innovative environmental intervention providing access and availability to F&V at the worksite and whether this access intervention is further enhanced by accompanying educational interventions. GTG will provide an important contribution to public health research and practice. Trial registration number NCT02729675, ClinicalTrials.gov PMID:29242108

Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1.

PubMed

Jansen, Jeroen P; Fleurence, Rachael; Devine, Beth; Itzler, Robbin; Barrett, Annabel; Hawkins, Neil; Lee, Karen; Boersma, Cornelis; Annemans, Lieven; Cappelleri, Joseph C

2011-06-01

Evidence-based health-care decision making requires comparisons of all relevant competing interventions. In the absence of randomized, controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best choice(s) of treatment. Mixed treatment comparisons, a special case of network meta-analysis, combine direct and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than a traditional meta-analysis. This report from the ISPOR Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on the interpretation of indirect treatment comparisons and network meta-analysis to assist policymakers and health-care professionals in using its findings for decision making. We start with an overview of how networks of randomized, controlled trials allow multiple treatment comparisons of competing interventions. Next, an introduction to the synthesis of the available evidence with a focus on terminology, assumptions, validity, and statistical methods is provided, followed by advice on critically reviewing and interpreting an indirect treatment comparison or network meta-analysis to inform decision making. We finish with a discussion of what to do if there are no direct or indirect treatment comparisons of randomized, controlled trials possible and a health-care decision still needs to be made. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

The design and methodology of premature ejaculation interventional studies

PubMed Central

2016-01-01

Large well-designed clinical efficacy and safety randomized clinical trials (RCTs) are required to achieve regulatory approval of new drug treatments. The objective of this article is to make recommendations for the criteria for defining and selecting the clinical trial study population, design and efficacy outcomes measures which comprise ideal premature ejaculation (PE) interventional trial methodology. Data on clinical trial design, epidemiology, definitions, dimensions and psychological impact of PE was reviewed, critiqued and incorporated into a series of recommendations for standardisation of PE clinical trial design, outcome measures and reporting using the principles of evidence based medicine. Data from PE interventional studies are only reliable, interpretable and capable of being generalised to patients with PE, when study populations are defined by the International Society for Sexual Medicine (ISSM) multivariate definition of PE. PE intervention trials should employ a double-blind RCT methodology and include placebo control, active standard drug control, and/or dose comparison trials. Ejaculatory latency time (ELT) and subject/partner outcome measures of control, personal/partner/relationship distress and other study-specific outcome measures should be used as outcome measures. There is currently no published literature which identifies a clinically significant threshold response to intervention. The ISSM definition of PE reflects the contemporary understanding of PE and represents the state-of-the-art multi-dimensional definition of PE and is recommended as the basis of diagnosis of PE for all PE clinical trials. PMID:27652224

Industry sponsorship bias in research findings: a network meta-analysis of LDL cholesterol reduction in randomised trials of statins

PubMed Central

Dias, Sofia; Ades, A E

2014-01-01

Objective To explore the risk of industry sponsorship bias in a systematically identified set of placebo controlled and active comparator trials of statins. Design Systematic review and network meta-analysis. Eligibility Open label and double blind randomised controlled trials comparing one statin with another at any dose or with control (placebo, diet, or usual care) for adults with, or at risk of developing, cardiovascular disease. Only trials that lasted longer than four weeks with more than 50 participants per trial arm were included. Two investigators assessed study eligibility. Data sources Bibliographic databases and reference lists of relevant articles published between 1 January 1985 and 10 March 2013. Data extraction One investigator extracted data and another confirmed accuracy. Main outcome measure Mean absolute change from baseline concentration of low density lipoprotein (LDL) cholesterol. Data synthesis Study level outcomes from randomised trials were combined using random effects network meta-analyses. Results We included 183 randomised controlled trials of statins, 103 of which were two-armed or multi-armed active comparator trials. When all of the existing randomised evidence was synthesised in network meta-analyses, there were clear differences in the LDL cholesterol lowering effects of individual statins at different doses. In general, higher doses resulted in higher reductions in baseline LDL cholesterol levels. Of a total of 146 industry sponsored trials, 64 were placebo controlled (43.8%). The corresponding number for the non-industry sponsored trials was 16 (43.2%). Of the 35 unique comparisons available in 37 non-industry sponsored trials, 31 were also available in industry sponsored trials. There were no systematic differences in magnitude between the LDL cholesterol lowering effects of individual statins observed in industry sponsored versus non-industry sponsored trials. In industry sponsored trials, the mean change from baseline LDL cholesterol level was on average 1.77 mg/dL (95% credible interval −11.12 to 7.66) lower than the change observed in non-industry sponsored trials. There was no detectable inconsistency in the evidence network. Conclusions Our analysis shows that the findings obtained from industry sponsored statin trials seem similar in magnitude as those in non-industry sources. There are actual differences in the effectiveness of individual statins at various doses that explain previously observed discrepancies between industry and non-industry sponsored trials. PMID:25281681

Project EX: A Program of Empirical Research on Adolescent Tobacco Use Cessation

PubMed Central

Sussman, Steve; McCuller, William J; Zheng, Hong; Pfingston, Yvonne M; Miyano, James; Dent, Clyde W

2004-01-01

This paper presents the Project EX research program. The historical background for Project EX is presented, including a brief summary of reasons youth fail to quit tobacco use, the disappointing status of previous cessation research, and the teen cessation trial that provided the template for the current project (Project TNT). Next, program development studies for Project EX are described. Through use of focus groups, a theme study (concept evaluation of written activity descriptions), a component study, and pilot studies, an eight-session program was developed. This program involves novel activities (e.g., "talk show enactments," games, and alternative medicine-type activities such as yoga and meditation) in combination with motivation enhancement and cognitive-behavioral strategies to motivate and instruct in cessation initiation and maintenance efforts. The outcomes of the first experimental trial of Project EX, a school-based clinic program, are described, followed by a posthoc analysis of its effects mediation. A second EX study, a multiple baseline single group pilot study design in Wuhan, China, is described next. Description of a second experimental trial follows, which tested EX with nicotine gum versus a natural herb. A third experimental trial that tests a classroom prevention/cessation version of EX is then introduced. Finally, the implications of this work are discussed. The intent-to-treat quit rate for Project EX is approximately 15% across studies, double that of a standard care comparison. Effects last up to a six-month post-program at regular and alternative high schools. Through a systematic protocol of empirical program development and field trials, an effective and replicable model teen tobacco use cessation program is established. Future cessation work might expand on this work.

Project EX: A Program of Empirical Research on Adolescent Tobacco Use Cessation

PubMed Central

Sussman, Steve; McCuller, William J; Zheng, Hong; Pfingston, Yvonne M; Miyano, James; Dent, Clyde W

2004-01-01

This paper presents the Project EX research program. The historical background for Project EX is presented, including a brief summary of reasons youth fail to quit tobacco use, the disappointing status of previous cessation research, and the teen cessation trial that provided the template for the current project (Project TNT). Next, program development studies for Project EX are described. Through use of focus groups, a theme study (concept evaluation of written activity descriptions), a component study, and pilot studies, an eight-session program was developed. This program involves novel activities (e.g., "talk show enactments," games, and alternative medicine-type activities such as yoga and meditation) in combination with motivation enhancement and cognitive-behavioral strategies to motivate and instruct in cessation initiation and maintenance efforts. The outcomes of the first experimental trial of Project EX, a school-based clinic program, are described, followed by a posthoc analysis of its effects mediation. A second EX study, a multiple baseline single group pilot study design in Wuhan, China, is described next. Description of a second experimental trial follows, which tested EX with nicotine gum versus a natural herb. A third experimental trial that tests a classroom prevention/cessation version of EX is then introduced. Finally, the implications of this work are discussed. The intent-to-treat quit rate for Project EX is approximately 15% across studies, double that of a standard care comparison. Effects last up to a six-month post-program at regular and alternative high schools. Through a systematic protocol of empirical program development and field trials, an effective and replicable model teen tobacco use cessation program is established. Future cessation work might expand on this work. PMID:19570278

Print versus a culturally-relevant Facebook and text message delivered intervention to promote physical activity in African American women: a randomized pilot trial.

PubMed

Joseph, Rodney P; Keller, Colleen; Adams, Marc A; Ainsworth, Barbara E

2015-03-27

African American women report insufficient physical activity and are disproportionally burdened by associated disease conditions; indicating the need for innovative approaches to promote physical activity in this underserved population. Social media platforms (i.e. Facebook) and text messaging represent potential mediums to promote physical activity. This paper reports the results of a randomized pilot trial evaluating a theory-based (Social Cognitive Theory) multi-component intervention using Facebook and text-messages to promote physical activity among African American women. Participants (N = 29) were randomly assigned to receive one of two multi-component physical activity interventions over 8 weeks: a culturally-relevant, Social Cognitive Theory-based, intervention delivered by Facebook and text message (FI) (n = 14), or a non-culturally tailored print-based intervention (PI) (n = 15) consisting of promotion brochures mailed to their home. The primary outcome of physical activity was assessed by ActiGraph GT3X+ accelerometers. Secondary outcomes included self-reported physical activity, physical activity-related psychosocial variables, and participant satisfaction. All randomized participants (N = 29) completed the study. Accelerometer measured physical activity showed that FI participants decreased sedentary time (FI = -74 minutes/week vs. PI = +118 minute/week) and increased light intensity (FI = +95 minutes/week vs. PI = +59 minutes/week) and moderate-lifestyle intensity physical activity (FI = + 27 minutes/week vs. PI = -34 minutes/week) in comparison to PI participants (all P's < .05). No between group differences for accelerometer measured moderate-to-vigorous intensity physical activity were observed (P > .05). Results of secondary outcomes showed that in comparison to the PI, FI participants self-reported greater increases in moderate-to-vigorous physical activity (FI = +62 minutes/week vs. PI = +6 minutes/week; P = .015) and had greater enhancements in self-regulation for physical activity (P < .001) and social support from family for physical activity (P = .044). Satisfaction with the FI was also high: 100% reported physical activity-related knowledge gains and 100% would recommend the program to a friend. A culturally-relevant Facebook and text message delivered physical activity program was associated with several positive outcomes, including decreased sedentary behavior, increased light- and moderate-lifestyle intensity physical activity, enhanced psychosocial outcomes, and high participant satisfaction. Future studies with larger samples are warranted to further explore the efficacy of technology-based approaches to promote physical activity among African American women. ClinicalTrials.gov NCT02372565 . Registered 25 February 2015.

Strategies to improve recruitment to randomised trials.

PubMed

Treweek, Shaun; Pitkethly, Marie; Cook, Jonathan; Fraser, Cynthia; Mitchell, Elizabeth; Sullivan, Frank; Jackson, Catherine; Taskila, Tyna K; Gardner, Heidi

2018-02-22

Recruiting participants to trials can be extremely difficult. Identifying strategies that improve trial recruitment would benefit both trialists and health research. To quantify the effects of strategies for improving recruitment of participants to randomised trials. A secondary objective is to assess the evidence for the effect of the research setting (e.g. primary care versus secondary care) on recruitment. We searched the Cochrane Methodology Review Group Specialised Register (CMR) in the Cochrane Library (July 2012, searched 11 February 2015); MEDLINE and MEDLINE In Process (OVID) (1946 to 10 February 2015); Embase (OVID) (1996 to 2015 Week 06); Science Citation Index & Social Science Citation Index (ISI) (2009 to 11 February 2015) and ERIC (EBSCO) (2009 to 11 February 2015). Randomised and quasi-randomised trials of methods to increase recruitment to randomised trials. This includes non-healthcare studies and studies recruiting to hypothetical trials. We excluded studies aiming to increase response rates to questionnaires or trial retention and those evaluating incentives and disincentives for clinicians to recruit participants. We extracted data on: the method evaluated; country in which the study was carried out; nature of the population; nature of the study setting; nature of the study to be recruited into; randomisation or quasi-randomisation method; and numbers and proportions in each intervention group. We used a risk difference to estimate the absolute improvement and the 95% confidence interval (CI) to describe the effect in individual trials. We assessed heterogeneity between trial results. We used GRADE to judge the certainty we had in the evidence coming from each comparison. We identified 68 eligible trials (24 new to this update) with more than 74,000 participants. There were 63 studies involving interventions aimed directly at trial participants, while five evaluated interventions aimed at people recruiting participants. All studies were in health care.We found 72 comparisons, but just three are supported by high-certainty evidence according to GRADE.1. Open trials rather than blinded, placebo trials. The absolute improvement was 10% (95% CI 7% to 13%).2. Telephone reminders to people who do not respond to a postal invitation. The absolute improvement was 6% (95% CI 3% to 9%). This result applies to trials that have low underlying recruitment. We are less certain for trials that start out with moderately good recruitment (i.e. over 10%).3. Using a particular, bespoke, user-testing approach to develop participant information leaflets. This method involved spending a lot of time working with the target population for recruitment to decide on the content, format and appearance of the participant information leaflet. This made little or no difference to recruitment: absolute improvement was 1% (95% CI -1% to 3%).We had moderate-certainty evidence for eight other comparisons; our confidence was reduced for most of these because the results came from a single study. Three of the methods were changes to trial management, three were changes to how potential participants received information, one was aimed at recruiters, and the last was a test of financial incentives. All of these comparisons would benefit from other researchers replicating the evaluation. There were no evaluations in paediatric trials.We had much less confidence in the other 61 comparisons because the studies had design flaws, were single studies, had very uncertain results or were hypothetical (mock) trials rather than real ones. The literature on interventions to improve recruitment to trials has plenty of variety but little depth. Only 3 of 72 comparisons are supported by high-certainty evidence according to GRADE: having an open trial and using telephone reminders to non-responders to postal interventions both increase recruitment; a specialised way of developing participant information leaflets had little or no effect. The methodology research community should improve the evidence base by replicating evaluations of existing strategies, rather than developing and testing new ones.

Pharmacological interventions for prevention or treatment of postoperative pain in people undergoing laparoscopic cholecystectomy.

PubMed

Gurusamy, Kurinchi Selvan; Vaughan, Jessica; Toon, Clare D; Davidson, Brian R

2014-03-28

While laparoscopic cholecystectomy is generally considered less painful than open surgery, pain is one of the important reasons for delayed discharge after day-surgery and overnight stay following laparoscopic cholecystectomy. The safety and effectiveness of different pharmacological interventions such as non-steroidal anti-inflammatory drugs, opioids, and anticonvulsant analgesics in people undergoing laparoscopic cholecystectomy is unknown. To assess the benefits and harms of different analgesics in people undergoing laparoscopic cholecystectomy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization International Clinical Trials Registry Platform portal (WHO ICTRP) to March 2013 to identify randomised clinical trials of relevance to this review. We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different pharmacological interventions with no intervention or inactive controls for outcomes related to benefit in this review. We considered comparative non-randomised studies with regards to treatment-related harms. We also considered trials that compared one class of drug with another class of drug for this review. Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). We included 25 trials with 2505 participants randomised to the different pharmacological agents and inactive controls. All the trials were at unclear risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Participants were allowed to take additional analgesics as required in 24 of the trials. The pharmacological interventions in all the included trials were aimed at preventing pain after laparoscopic cholecystectomy. There were considerable differences in the pharmacological agents used and the methods of administration. The estimated effects of the intervention on the proportion of participants who were discharged as day-surgery, the length of hospital stay, or the time taken to return to work were imprecise in all the comparisons in which these outcomes were reported (very low quality evidence). There was no mortality in any of the groups in the two trials that reported mortality (183 participants, very low quality evidence). Differences in serious morbidity outcomes between the groups were imprecise across all the comparisons (very low quality evidence). None of the trials reported patient quality of life or time taken to return to normal activity. The pain at 4 to 8 hours was generally reduced by about 1 to 2 cm on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). The pain at 9 to 24 hours was generally reduced by about 0.5 cm (a modest reduction) on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). There is evidence of very low quality that different pharmacological agents including non-steroidal anti-inflammatory drugs, opioid analgesics, and anticonvulsant analgesics reduce pain scores in people at low anaesthetic risk undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.

Methods of preventing bacterial sepsis and wound complications after liver transplantation.

PubMed

Gurusamy, Kurinchi Selvan; Nagendran, Myura; Davidson, Brian R

2014-03-05

Bacterial sepsis and wound complications after liver transplantation increase mortality, morbidity, or hospital stay and are likely to increase overall transplant costs. All liver transplantation patients receive antibiotic prophylaxis. This is an update of our 2008 Cochrane systematic review on the same topic in which we identified seven randomised clinical trials. To assess the benefits and harms of different methods aimed at preventing bacterial sepsis and wound complications in people undergoing liver transplantation. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to February 2013. We included only randomised clinical trials irrespective of language or publication status. We excluded quasi-randomised and other observational studies for assessment of benefits, but not for harms. Two review authors collected the data independently. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) using fixed-effect and the random-effects models based on available-case analysis. We identified only seven trials for inclusion, including 614 participants. Only one trial was of low risk of bias risk. Overall, the quality of evidence was very low. There were five comparisons in the seven trials: selective bowel decontamination versus inactive control; selective bowel decontamination versus prebiotics with probiotics; selective bowel decontamination versus prebiotics; prebiotics with probiotics versus prebiotics; and granulocyte-colony stimulating factor (G-CSF) versus control. Four trials compared selective bowel decontamination versus placebo or no treatment. In one trial, participants were randomised to selective bowel decontamination, active lactobacillus with fibres (probiotic with prebiotic), or to inactivated lactobacillus with fibres (prebiotic). In one trial, active lactobacillus with fibres (probiotic with prebiotic) was compared with inactive lactobacillus with fibres (prebiotic). In the remaining trial, different doses of G-CSF and placebo were compared. There was no trial comparing different antibiotic prophylactic regimens in people undergoing liver transplantation. Most trials included adults undergoing elective liver transplantation. There was no significant difference in proportion of people who died or required retransplantation between the intervention and control groups in any of the five comparison groups. MORTALITY There were no differences between 190 participants (three trials); 5/87 (adjusted proportion: 6.2%) in selective bowel decontamination group versus 7/103 (6.8%) in inactive control group; RR 0.91 (95% CI 0.31 to 2.72); 63 participants (one trial); 0/32 (0%) in selective bowel decontamination group versus 0/31 (0%) in prebiotics with probiotics group; RR - not estimable; 64 participants (one trial); 0/32 (0%) in selective bowel decontamination group versus 0/32 (0%) in prebiotics group; RR - not estimable; 129 participants (two trials); 0/64 (0%) in prebiotics with probiotics group versus 0/65 (0%) in prebiotics group; RR - not estimable; and 194 participants (one trial); 22/124 (17.7%) in G-CSF group versus 10/70 (14.3%) in placebo group; RR 1.24 (95% 0.62 to 2.47). RETRANSPLANTATION There were no differences between 132 participants (two trials); 4/58 (adjusted proportion: 6.9%) in selective bowel decontamination group versus 6/74 (8.1%) in inactive control group; RR 0.85 (95% CI 0.26 to 2.85); 63 participants (one trial); 1/32 (3.1%) in selective bowel decontamination group versus 0/31 (0%) in prebiotics with probiotics group; RR 2.91 (0.12 to 68.81); 64 participants (one trial); 1/32 (3.1%) in selective bowel decontamination group versus 0/32 (0%) in prebiotics group; RR 3.00 (95% CI 0.13 to 71.00); 129 participants (two trials); 0/64 (0%) in prebiotics with probiotics group versus 1/65 (1.5%) in prebiotics group; RR 0.33 (95% CI 0.01 to 7.9); and 194 participants (one trial); 10/124 (7.1%) in G-CSF group versus 5/70 (7.1%) in placebo group; RR 1.13 (95% CI 0.4 to 3.17).There was no significant difference in the graft rejections, intensive therapy unit stay, or hospital stay between the intervention and control groups in any of the comparisons. Overall, 193/611 participants (31.6%) developed infective complications. The proportion of people who developed infective complications and the number of infective complication episodes were significantly higher in the selective bowel decontamination group than in the prebiotics with probiotics group (1 study; 63 participants; 15/32 (46.9%) in selective bowel decontamination group versus 4/31 (12.9%) in prebiotics with probiotics group; RR 3.63; 95% CI 1.36 to 9.74 and 23/32 participants (0.72 infective complications per participant) in selective bowel decontamination group versus 4/31 participants (0.13 infective complications per participant) in prebiotics with probiotics group; rate ratio 5.58; 95% CI 1.94 to 16.09). There was no significant difference between the proportion of participants who developed infection and the number of infection episodes between the intervention group and control group in any of the other comparisons.No trials reported quality of life and overall serious adverse events. Currently, there is no clear evidence for any intervention offering significant benefits in the reduction of bacterial infections and wound complications in liver transplantation. Selective bowel decontamination may even increase the rate of infections compared with prebiotics with probiotics. The confidence intervals were wide and further randomised clinical trials of low risk of bias are necessary.

Impact of Short- and Long-term Tai Chi Mind-Body Exercise Training on Cognitive Function in Healthy Adults: Results From a Hybrid Observational Study and Randomized Trial.

PubMed

Walsh, Jacquelyn N; Manor, Brad; Hausdorff, Jeffrey; Novak, Vera; Lipsitz, Lewis; Gow, Brian; Macklin, Eric A; Peng, Chung-Kang; Wayne, Peter M

2015-07-01

Cognitive decline amongst older adults is a significant public health concern. There is growing interest in behavioral interventions, including exercise, for improving cognition. Studies to date suggest tai chi (TC) may be a safe and potentially effective exercise for preserving cognitive function with aging; however, its short-term and potential long-term impact on physically active, healthy adults is unclear. To compare differences in cognitive function among long-term TC expert practitioners and age-matched and gender-matched TC-naïve adults and to determine the effects of short-term TC training on measures of cognitive function in healthy, nonsedentary adults. A hybrid design including an observational comparison and a 2-arm randomized clinical trial (RCT). Healthy, nonsedentary, TC-naive adults (50 y-79 y) and age-matched and gender-matched long-term TC experts. A cross-sectional comparison of cognitive function in healthy TC-naïve (n=60) and TC expert (24.5 y ÷ 12 y experience; n=27) adults: TC-naïve adults then completed a 6-month, 2-arm, wait-list randomized clinical trial of TC training. Six measures of cognitive function were assessed for both cross-sectional and longitudinal comparisons. TC experts exhibited trends towards better scores on all cognitive measures, significantly so for category fluency (P=.01), as well as a composite z score summarizing all 6 cognitive assessments (P=.03). In contrast, random assignment to 6 months of TC training in TC-naïve adults did not significantly improve any measures of cognitive function. In healthy nonsedentary adults, long-term TC training may help preserve cognitive function; however, the effect of short-term TC training in healthy adults remains unclear. ClinicalTrials.gov NCT01340365.

Does physical activity impact on presenteeism and other indicators of workplace well-being?

PubMed

Brown, Helen E; Gilson, Nicholas D; Burton, Nicola W; Brown, Wendy J

2011-03-01

The term 'presenteeism' is a relatively new concept in workplace health, and has come to signify being at work despite poor health and performing below par. Presenteeism, which is potentially critical to employers, has been associated with a range of psychosocial outcome measures, such as poor mental health and employee well-being. Physical activity is a potential strategy for reducing presenteeism, and for improving the mental health of employees. This article reviews evidence on the relationships between physical activity and employee well-being and presenteeism in the workplace, and identifies directions for research in an emerging field. Electronic and manual literature searches were used to identify 20 articles that met the inclusion criteria. These included 13 intervention trials (8 randomized controlled trials, 5 comparison trials) and 7 observational studies (3 cohort, 4 cross-sectional). Outcome measures were grouped into 'workplace well-being', 'psychosocial well-being' and 'physical well-being'. Studies measured a wide variety of outcomes, with absenteeism being the most commonly assessed. Evidence indicated a positive association between physical activity and psychosocial health in employees, particularly for quality of life and emotional well-being. However, findings were inconclusive as to the role of physical activity in promoting workplace well-being. Only one study reported on presenteeism, with mixed evidence for outcomes. This article indicates that physical activity and employee psychosocial health are positively related, but there is limited evidence of a relationship between physical activity and presenteeism. A standardized definition of presenteeism and an appropriate evaluation tool are key research priorities if the complex relationships between physical activity and workplace well-being are to be better understood. © 2011 Adis Data Information BV. All rights reserved.

Strategies to improve the implementation of healthy eating, physical activity and obesity prevention policies, practices or programmes within childcare services.

PubMed

Wolfenden, Luke; Jones, Jannah; Williams, Christopher M; Finch, Meghan; Wyse, Rebecca J; Kingsland, Melanie; Tzelepis, Flora; Wiggers, John; Williams, Amanda J; Seward, Kirsty; Small, Tameka; Welch, Vivian; Booth, Debbie; Yoong, Sze Lin

2016-10-04

Despite the existence of effective interventions and best-practice guideline recommendations for childcare services to implement policies, practices and programmes to promote child healthy eating, physical activity and prevent unhealthy weight gain, many services fail to do so. The primary aim of the review was to examine the effectiveness of strategies aimed at improving the implementation of policies, practices or programmes by childcare services that promote child healthy eating, physical activity and/or obesity prevention. The secondary aims of the review were to:1. describe the impact of such strategies on childcare service staff knowledge, skills or attitudes;2. describe the cost or cost-effectiveness of such strategies;3. describe any adverse effects of such strategies on childcare services, service staff or children;4. examine the effect of such strategies on child diet, physical activity or weight status. We searched the following electronic databases on 3 August 2015: the Cochrane Central Register of Controlled trials (CENTRAL), MEDLINE, MEDLINE In Process, EMBASE, PsycINFO, ERIC, CINAHL and SCOPUS. We also searched reference lists of included trials, handsearched two international implementation science journals and searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp/) and ClinicalTrials.gov (www.clinicaltrials.gov). We included any study (randomised or non-randomised) with a parallel control group that compared any strategy to improve the implementation of a healthy eating, physical activity or obesity prevention policy, practice or programme by staff of centre-based childcare services to no intervention, 'usual' practice or an alternative strategy. The review authors independently screened abstracts and titles, extracted trial data and assessed risk of bias in pairs; we resolved discrepancies via consensus. Heterogeneity across studies precluded pooling of data and undertaking quantitative assessment via meta-analysis. However, we narratively synthesised the trial findings by describing the effect size of the primary outcome measure for policy or practice implementation (or the median of such measures where a single primary outcome was not stated). We identified 10 trials as eligible and included them in the review. The trials sought to improve the implementation of policies and practices targeting healthy eating (two trials), physical activity (two trials) or both healthy eating and physical activity (six trials). Collectively the implementation strategies tested in the 10 trials included educational materials, educational meetings, audit and feedback, opinion leaders, small incentives or grants, educational outreach visits or academic detailing. A total of 1053 childcare services participated across all trials. Of the 10 trials, eight examined implementation strategies versus a usual practice control and two compared alternative implementation strategies. There was considerable study heterogeneity. We judged all studies as having high risk of bias for at least one domain.It is uncertain whether the strategies tested improved the implementation of policies, practices or programmes that promote child healthy eating, physical activity and/or obesity prevention. No intervention improved the implementation of all policies and practices targeted by the implementation strategies relative to a comparison group. Of the eight trials that compared an implementation strategy to usual practice or a no intervention control, however, seven reported improvements in the implementation of at least one of the targeted policies or practices relative to control. For these trials the effect on the primary implementation outcome was as follows: among the three trials that reported score-based measures of implementation the scores ranged from 1 to 5.1; across four trials reporting the proportion of staff or services implementing a specific policy or practice this ranged from 0% to 9.5%; and in three trials reporting the time (per day or week) staff or services spent implementing a policy or practice this ranged from 4.3 minutes to 7.7 minutes. The review findings also indicate that is it uncertain whether such interventions improve childcare service staff knowledge or attitudes (two trials), child physical activity (two trials), child weight status (two trials) or child diet (one trial). None of the included trials reported on the cost or cost-effectiveness of the intervention. One trial assessed the adverse effects of a physical activity intervention and found no difference in rates of child injury between groups. For all review outcomes, we rated the quality of the evidence as very low. The primary limitation of the review was the lack of conventional terminology in implementation science, which may have resulted in potentially relevant studies failing to be identified based on the search terms used in this review. Current research provides weak and inconsistent evidence of the effectiveness of such strategies in improving the implementation of policies and practices, childcare service staff knowledge or attitudes, or child diet, physical activity or weight status. Further research in the field is required.

The Congenital Heart Surgeons Society Datacenter: unique attributes as a research organization.

PubMed

Caldarone, Christopher A; Williams, William G

2010-01-01

Over the last 25 years, the Congenital Heart Surgeons Society (CHSS) has evolved from an informal club to a mature organization. A central feature of the CHSS has been dedication to evaluating outcomes of congenital heart surgery across a wide array of clinical diagnoses. These research activities have been orchestrated through the CHSS Datacenter, which has developed a unique organizational structure that has strengths and weaknesses in comparison to other research organizational structures (e.g., prospective randomized trials, registries, etc). This review will highlight the unique attributes of the CHSS Datacenter with emphasis on the Datacenter's strengths and weaknesses in comparison to other organizational structures. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Constructing common cohorts from trials with overlapping eligibility criteria: implications for comparing effect sizes between trials.

PubMed

Mount, David L; Feeney, Patricia; Fabricatore, Anthony N; Coday, Mace; Bahnson, Judy; Byington, Robert; Phelan, Suzanne; Wilmoth, Sharon; Knowler, William C; Hramiak, Irene; Osei, Kwame; Sweeney, Mary Ellen; Espeland, Mark A

2009-10-01

Comparing findings from separate trials is necessary to choose among treatment options, however differences among study cohorts may impede these comparisons. As a case study, to examine the overlap of study cohorts in two large randomized controlled clinical trials that assess interventions to reduce risk of major cardiovascular disease events in adults with type 2 diabetes in order to explore the feasibility of cross-trial comparisons The Action for Health in Diabetes (Look AHEAD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials enrolled 5145 and 10,251 adults with type 2 diabetes, respectively. Look AHEAD assesses the efficacy of an intensive lifestyle intervention designed to produce weight loss; ACCORD tests pharmacological therapies for control of glycemia, hyperlipidemia, and hypertension. Incidence of major cardiovascular disease events is the primary outcome for both trials. A sample was constructed to include participants from each trial who appeared to meet eligibility criteria and be appropriate candidates for the other trial's interventions. Demographic characteristics, health status, and outcomes of members and nonmembers of this constructed sample were compared. Nearly 80% of Look AHEAD participants were projected to be ineligible for ACCORD; ineligibility was primarily due to better glycemic control or no early history of cardiovascular disease. Approximately 30% of ACCORD participants were projected to be ineligible for Look AHEAD, often for reasons linked to poorer health. The characteristics of participants projected to be jointly eligible for both trials continued to reflect differences between trials according to factors likely linked to retention, adherence, and study outcomes. Accurate ascertainment of cross-trial eligibility was hampered by differences between protocols. Despite several similarities, the Look AHEAD and ACCORD cohorts represent distinct populations. Even within the subsets of participants who appear to be eligible and appropriate candidates for trials of both modes of intervention, differences remained. Direct comparisons of results from separate trials of lifestyle and pharmacologic interventions are compromised by marked differences in enrolled cohorts.

Parent-only interventions for childhood overweight or obesity in children aged 5 to 11 years.

PubMed

Loveman, Emma; Al-Khudairy, Lena; Johnson, Rebecca E; Robertson, Wendy; Colquitt, Jill L; Mead, Emma L; Ells, Louisa J; Metzendorf, Maria-Inti; Rees, Karen

2015-12-21

Child and adolescent overweight and obesity have increased globally, and are associated with short- and long-term health consequences. To assess the efficacy of diet, physical activity and behavioural interventions delivered to parents only for the treatment of overweight and obesity in children aged 5 to 11 years. We performed a systematic literature search of databases including the Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS as well trial registers. We checked references of identified trials and systematic reviews. We applied no language restrictions. The date of the last search was March 2015 for all databases. We selected randomised controlled trials (RCTs) of diet, physical activity and behavioural interventions delivered to parents only for treating overweight or obesity in children aged 5 to 11 years. Two review authors independently assessed trials for risk of bias and evaluated overall study quality using the GRADE instrument. Where necessary, we contacted authors for additional information. We included 20 RCTs, including 3057 participants. The number of participants ranged per trial between 15 and 645. Follow-up ranged between 24 weeks and two years. Eighteen trials were parallel RCTs and two were cluster RCTs. Twelve RCTs had two comparisons and eight RCTs had three comparisons. The interventions varied widely; the duration, content, delivery and follow-up of the interventions were heterogeneous. The comparators also differed. This review categorised the comparisons into four groups: parent-only versus parent-child, parent-only versus waiting list controls, parent-only versus minimal contact interventions and parent-only versus other parent-only interventions.Trial quality was generally low with a large proportion of trials rated as high risk of bias on individual risk of bias criteria.In trials comparing a parent-only intervention with a parent-child intervention, the body mass index (BMI) z score change showed a mean difference (MD) at the longest follow-up period (10 to 24 months) of -0.04 (95% confidence interval (CI) -0.15 to 0.08); P = 0.56; 267 participants; 3 trials; low quality evidence. In trials comparing a parent-only intervention with a waiting list control, the BMI z score change in favour of the parent-only intervention at the longest follow-up period (10-12 months) had an MD of -0.10 (95% CI -0.19 to -0.01); P = 0.04; 136 participants; 2 trials; low quality evidence. BMI z score change of parent-only interventions when compared with minimal contact control interventions at the longest follow-up period (9 to 12 months) showed an MD of 0.01 (95% CI -0.07 to 0.09); P = 0.81; 165 participants; 1 trial; low quality evidence. There were few similarities between interventions and comparators across the included trials in the parent-only intervention versus other parent-only interventions and we did not pool these data. Generally, these trials did not show substantial differences between their respective parent-only groups on BMI outcomes.Other outcomes such as behavioural measures, parent-child relationships and health-related quality of life were reported inconsistently. Adverse effects of the interventions were generally not reported, two trials stated that there were no serious adverse effects. No trials reported on all-cause mortality, morbidity or socioeconomic effects.All results need to be interpreted cautiously because of their low quality, the heterogeneous interventions and comparators, and the high rates of non-completion. Parent-only interventions may be an effective treatment option for overweight or obese children aged 5 to 11 years when compared with waiting list controls. Parent-only interventions had similar effects compared with parent-child interventions and compared with those with minimal contact controls. However, the evidence is at present limited; some of the trials had a high risk of bias with loss to follow-up being a particular issue and there was a lack of evidence for several important outcomes. The systematic review has identified 10 ongoing trials that have a parent-only arm, which will contribute to future updates. These trials will improve the robustness of the analyses by type of comparator, and may permit subgroup analysis by intervention component and the setting. Trial reports should provide adequate details about the interventions to be replicated by others. There is a need to conduct and report cost-effectiveness analyses in future trials in order to establish whether parent-only interventions are more cost-effective than parent-child interventions.

Randomized trial of a telephone-based weight loss intervention in postmenopausal women with breast cancer receiving letrozole: the LISA trial.

PubMed

Goodwin, Pamela J; Segal, Roanne J; Vallis, Michael; Ligibel, Jennifer A; Pond, Gregory R; Robidoux, André; Blackburn, George L; Findlay, Brian; Gralow, Julie R; Mukherjee, Som; Levine, Mark; Pritchard, Kathleen I

2014-07-20

Obesity is associated with poor outcomes in women with operable breast cancer. Lifestyle interventions (LIs) that help women reduce their weight may improve outcomes. We conducted a multicenter randomized trial comparing mail-based delivery of general health information alone or combined with a 24-month standardized, telephone-based LI that included diet (500 to 1,000 kcal per day deficit) and physical activity (150 to 200 minutes of moderate-intensity physical activity per week) goals to achieve weight loss (up to 10%). Women receiving adjuvant letrozole for T1-3N0-3M0 breast cancer with a body mass index (BMI) ≥ 24 kg/m(2) were eligible. Weight was measured in the clinic, and self-report physical activity, quality-of-life (QOL), and diet questionnaires were completed. The primary outcome was disease-free survival. Accrual was terminated at 338 of 2,150 planned patients because of loss of funding. Mean weight loss was significantly (P < .001) greater in the LI arm versus the comparison arm (4.3 v 0.6 kg or 5.3% v 0.7% at 6 months and 3.1 v 0.3 kg or 3.6% v 0.4% at 24 months) and occurred consistently across strata (BMI 24 to < 30 v ≥ 30 kg/m(2); prior v no prior adjuvant chemotherapy). Weight loss was greatest in those with higher baseline levels of moderate-intensity physical activity or improvement in QOL. Hospitalization rates and medical events were similar. A telephone-based LI led to significant weight loss that was still evident at 24 months, without adverse effects on QOL, hospitalizations, or medical events. Adequately powered randomized trials with cancer end points are needed. © 2014 by American Society of Clinical Oncology.

Inhibition in motor imagery: a novel action mode switching paradigm.

PubMed

Rieger, Martina; Dahm, Stephan F; Koch, Iring

2017-04-01

Motor imagery requires that actual movements are prevented (i.e., inhibited) from execution. To investigate at what level inhibition takes place in motor imagery, we developed a novel action mode switching paradigm. Participants imagined (indicating only start and end) and executed movements from start buttons to target buttons, and we analyzed trial sequence effects. Trial sequences depended on current action mode (imagination or execution), previous action mode (pure blocks/same mode, mixed blocks/same mode, or mixed blocks/other mode), and movement sequence (action repetition, hand repetition, or hand alternation). Results provided evidence for global inhibition (indicated by switch benefits in execution-imagination (E-I)-sequences in comparison to I-I-sequences), effector-specific inhibition (indicated by hand repetition costs after an imagination trial), and target inhibition (indicated by target repetition benefits in I-I-sequences). No evidence for subthreshold motor activation or action-specific inhibition (inhibition of the movement of an effector to a specific target) was obtained. Two (global inhibition and effector-specific inhibition) of the three observed mechanisms are active inhibition mechanisms. In conclusion, motor imagery is not simply a weaker form of execution, which often is implied in views focusing on similarities between imagination and execution.

Composition, Stability, and Bioavailability of Garlic Products Being Used in a Clinical Trial

PubMed Central

Lawson, Larry D.; Gardner, Christopher D.

2008-01-01

In support of a new clinical trial designed to compare the effects of crushed fresh garlic and two types of garlic supplement tablets (enteric-coated dried fresh garlic and dried aged garlic extract) on serum lipids, the three garlic products have been characterized for (a) composition (14 sulfur and 2 non-sulfur compounds), (b) stability of suspected active compounds, and (c) availability of allyl thiosulfinates (mainly allicin) under both simulated gastrointestinal (tablet dissolution) conditions and in vivo. The allyl thiosulfinates of blended fresh garlic were stable for at least two years when stored at −80 °C. The dissolution release of thiosulfinates from the enteric-coated garlic tablets was found to be >95%. The bioavailability of allyl thiosulfinates from these tablets, measured as breath allyl methyl sulfide, was found to be complete and equivalent to that of crushed fresh garlic. S-allylcysteine was stable for 12 months at ambient temperature. The stability of the suspected active compounds under the conditions of the study and the bioavailability of allyl thiosulfinates from the dried garlic supplement have validated the use of these preparations for comparison in a clinical trial. PMID:16076102

Computer-Delivered and Web-Based Interventions to Improve Depression, Anxiety, and Psychological Well-Being of University Students: A Systematic Review and Meta-Analysis

PubMed Central

Morriss, Richard; Glazebrook, Cris

2014-01-01

Background Depression and anxiety are common mental health difficulties experienced by university students and can impair academic and social functioning. Students are limited in seeking help from professionals. As university students are highly connected to digital technologies, Web-based and computer-delivered interventions could be used to improve students’ mental health. The effectiveness of these intervention types requires investigation to identify whether these are viable prevention strategies for university students. Objective The intent of the study was to systematically review and analyze trials of Web-based and computer-delivered interventions to improve depression, anxiety, psychological distress, and stress in university students. Methods Several databases were searched using keywords relating to higher education students, mental health, and eHealth interventions. The eligibility criteria for studies included in the review were: (1) the study aimed to improve symptoms relating to depression, anxiety, psychological distress, and stress, (2) the study involved computer-delivered or Web-based interventions accessed via computer, laptop, or tablet, (3) the study was a randomized controlled trial, and (4) the study was trialed on higher education students. Trials were reviewed and outcome data analyzed through random effects meta-analyses for each outcome and each type of trial arm comparison. Cochrane Collaboration risk of bias tool was used to assess study quality. Results A total of 17 trials were identified, in which seven were the same three interventions on separate samples; 14 reported sufficient information for meta-analysis. The majority (n=13) were website-delivered and nine interventions were based on cognitive behavioral therapy (CBT). A total of 1795 participants were randomized and 1480 analyzed. Risk of bias was considered moderate, as many publications did not sufficiently report their methods and seven explicitly conducted completers’ analyses. In comparison to the inactive control, sensitivity meta-analyses supported intervention in improving anxiety (pooled standardized mean difference [SMD] −0.56; 95% CI −0.77 to −0.35, P<.001), depression (pooled SMD −0.43; 95% CI −0.63 to −0.22, P<.001), and stress (pooled SMD −0.73; 95% CI −1.27 to −0.19, P=.008). In comparison to active controls, sensitivity analyses did not support either condition for anxiety (pooled SMD −0.18; 95% CI −0.98 to 0.62, P=.66) or depression (pooled SMD −0.28; 95% CI −0.75 to −0.20, P=.25). In contrast to a comparison intervention, neither condition was supported in sensitivity analyses for anxiety (pooled SMD −0.10; 95% CI −0.39 to 0.18, P=.48) or depression (pooled SMD −0.33; 95% CI −0.43 to 1.09, P=.40). Conclusions The findings suggest Web-based and computer-delivered interventions can be effective in improving students’ depression, anxiety, and stress outcomes when compared to inactive controls, but some caution is needed when compared to other trial arms and methodological issues were noticeable. Interventions need to be trialed on more heterogeneous student samples and would benefit from user evaluation. Future trials should address methodological considerations to improve reporting of trial quality and address post-intervention skewed data. PMID:24836465

Effect of race/ethnicity on participation in HIV vaccine trials and comparison to other trials of biomedical prevention.

PubMed

Dhalla, Shayesta; Poole, Gary

2014-01-01

Racial/ethnic minorities are underrepresented in actual HIV vaccine trials in North America, and willingness to participate (WTP) and retention in an HIV vaccine trial may differ from that in Whites. In this review, the authors identified HIV vaccine preparedness studies (VPS) in North America in high-risk populations that examined the relationship between race/ethnicity and WTP in a preventive phase 3 HIV vaccine trial, and the relationship to retention. Studies were categorized by risk group, and comparison group (Whites vs. non-Whites). Other types of trials of biomedical prevention were also identified, and WTP and retention rates were compared and contrasted to actual HIV vaccine trials. In the studies identified, WTP in a hypothetical trial HIV vaccine trial did not differ by race/ethnicity. In contrast, actual HIV vaccine trials, an HIV acquisition trial, and a phase 2B preexposure prophylaxis (PrEP) trial have enrolled a large percentage of White men. Human papilloma virus (HPV) privately-funded trials have also enrolled a large number of Whites, due to convenience sampling. Retention in the HIV acquisition trial was lower in African-Americans compared with Whites. Strategies to increase WTP and enhanced retention (ER) strategies may help in recruiting and retaining minority participants in actual HIV vaccine trials and other trials of biomedical prevention.

Using Wearable Sensors and Machine Learning Models to Separate Functional Upper Extremity Use From Walking-Associated Arm Movements.

PubMed

McLeod, Adam; Bochniewicz, Elaine M; Lum, Peter S; Holley, Rahsaan J; Emmer, Geoff; Dromerick, Alexander W

2016-02-01

To improve measurement of upper extremity (UE) use in the community by evaluating the feasibility of using body-worn sensor data and machine learning models to distinguish productive prehensile and bimanual UE activity use from extraneous movements associated with walking. Comparison of machine learning classification models with criterion standard of manually scored videos of performance in UE prosthesis users. Rehabilitation hospital training apartment. Convenience sample of UE prosthesis users (n=5) and controls (n=13) similar in age and hand dominance (N=18). Participants were filmed executing a series of functional activities; a trained observer annotated each frame to indicate either UE movement directed at functional activity or walking. Synchronized data from an inertial sensor attached to the dominant wrist were similarly classified as indicating either a functional use or walking. These data were used to train 3 classification models to predict the functional versus walking state given the associated sensor information. Models were trained over 4 trials: on UE amputees and controls and both within subject and across subject. Model performance was also examined with and without preprocessing (centering) in the across-subject trials. Percent correct classification. With the exception of the amputee/across-subject trial, at least 1 model classified >95% of test data correctly for all trial types. The top performer in the amputee/across-subject trial classified 85% of test examples correctly. We have demonstrated that computationally lightweight classification models can use inertial data collected from wrist-worn sensors to reliably distinguish prosthetic UE movements during functional use from walking-associated movement. This approach has promise in objectively measuring real-world UE use of prosthetic limbs and may be helpful in clinical trials and in measuring response to treatment of other UE pathologies. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Promoting physical activity in sedentary elderly Malays with type 2 diabetes: a protocol for randomised controlled trial.

PubMed

Sazlina, Shariff-Ghazali; Browning, Colette Joy; Yasin, Shajahan

2012-01-01

Like many countries Malaysia is facing an increase in the number of people with type 2 diabetes mellitus diabetes (T2DM) and modifiable lifestyle factors such as sedentary behaviour are important drivers of this increase. The level of physical activity is low among elderly Malay people. In Malaysia, strategies to promote physical activity in elderly Malay people with T2DM are not well documented in the research literature. This paper discusses an intervention to increase physical activity in elderly Malay people with T2DM. The aim of our study was to evaluate the effectiveness of personalised feedback alone and in combination with peer support in promoting and maintaining physical activity in comparison with usual care. A three-arm randomised controlled trial will be conducted among sedentary Malay adults aged 60 years and above with T2DM attending an urban primary healthcare clinic in Malaysia. The participants will be randomised into three groups for a 12-week intervention with a follow-up at 24 and 36 weeks to assess adherence. The primary outcome of this study is pedometer-determined physical activity. Glycaemic and blood pressure control, body composition, cardiorespiratory fitness, balance, lipid profile, health-related quality of life, psychological well-being, social support and self-efficacy for exercise are the secondary measures. Linear mixed models will be used to determine the effect of the intervention over time and between groups. ETHICAL AND DISSEMINATION: The Monash University Human Research Ethics Committee and the Malaysian Ministry of Health's Medical Research Ethics Committee approved this protocol. The findings of this study will be presented at international conferences and published in peer-reviewed journals. This study protocol has been registered with the Malaysian National Medical Research Registry and with the Current Controlled Trial Ltd (http://www.controlled-trials.com/ISRCTN71447000/).

Pharmacological interventions for acute pancreatitis.

PubMed

Moggia, Elisabetta; Koti, Rahul; Belgaumkar, Ajay P; Fazio, Federico; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-21

In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. To assess the effects of different pharmacological interventions in people with acute pancreatitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials. We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model. We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials. seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life. Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

A mobile phone application for the assessment and management of youth mental health problems in primary care: health service outcomes from a randomised controlled trial of mobiletype.

PubMed

Reid, Sophie C; Kauer, Sylvia D; Hearps, Stephen J C; Crooke, Alexander H D; Khor, Angela S; Sanci, Lena A; Patton, George C

2013-06-19

GPs detect at best 50c of mental health problems in young people. Barriers to detecting mental health problems include lack of screening tools, limited appointment times and young people's reluctance to report mental health symptoms to GPs. The mobiletype program is a mobile phone mental health assessment and management application which monitors mood, stress and everyday activities then transmits this information to general practitioners (GPs) via a secure website in summary format for medical review. The current aims were to examine: (i) mobiletype as a clinical assistance tool, ii) doctor-patient rapport and, iii) pathways to care. We conducted a randomised controlled trial in primary care with patients aged 14 to 24 years recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress and daily activities were monitored) or the attention-comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants and researchers were blind to group allocation at randomisation. GPs assessed the mobiletype program as a clinical assistant tool. Doctor-patient rapport was assessed using the General Practice Assessment Questionnaire Communication and Enablement subscales, and the Trust in Physician Scale (TPS). Pathways to care was measured using The Party Project's Exit Interview. Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention n = 68, attention-comparison n = 46). T-tests showed that the intervention program increased understanding of patient mental health, assisted in decisions about medication/referral and helped in diagnosis when compared to the attention-comparison program. Mixed model analysis showed no differences in GP-patient rapport nor in pathways to care. We conducted the first RCT of a mobile phone application in the mental health assessment and management of youth mental health in primary care. This study suggests that mobiletype has much to offer GPs in the often difficult and time-consuming task of assessment and management of youth mental health problems in primary care. ClinicalTrials.gov NCT00794222.

A mobile phone application for the assessment and management of youth mental health problems in primary care: a randomised controlled trial.

PubMed

Reid, Sophie C; Kauer, Sylvia D; Hearps, Stephen J C; Crooke, Alexander H D; Khor, Angela S; Sanci, Lena A; Patton, George C

2011-11-29

Over 75% of mental health problems begin in adolescence and primary care has been identified as the target setting for mental health intervention by the World Health Organisation. The mobiletype program is a mental health assessment and management mobile phone application which monitors mood, stress, coping strategies, activities, eating, sleeping, exercise patterns, and alcohol and cannabis use at least daily, and transmits this information to general practitioners (GPs) via a secure website in summary format for medical review. We conducted a randomised controlled trial in primary care to examine the mental health benefits of the mobiletype program. Patients aged 14 to 24 years were recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress, and daily activities were monitored) or the attention comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants, and researchers were blind to group allocation at randomisation. Participants completed pre-, post-, and 6-week post-test measures of the Depression, Anxiety, Stress Scale and an Emotional Self Awareness (ESA) Scale. Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention group n = 68, comparison group n = 46). Mixed model analyses revealed a significant group by time interaction on ESA with a medium size of effect suggesting that the mobiletype program significantly increases ESA compared to an attention comparison. There was no significant group by time interaction for depression, anxiety, or stress, but a medium to large significant main effect for time for each of these mental health measures. Post-hoc analyses suggested that participation in the RCT lead to enhanced GP mental health care at pre-test and improved mental health outcomes. Monitoring mental health symptoms appears to increase ESA and implementing a mental health program in primary care and providing frequent reminders, clinical resources, and support to GPs substantially improved mental health outcomes for the sample as a whole. ClinicalTrials.gov NCT00794222.

Interventions for promoting the initiation of breastfeeding.

PubMed

Balogun, Olukunmi O; O'Sullivan, Elizabeth J; McFadden, Alison; Ota, Erika; Gavine, Anna; Garner, Christine D; Renfrew, Mary J; MacGillivray, Stephen

2016-11-09

Despite the widely documented risks of not breastfeeding, initiation rates remain relatively low in many high-income countries, particularly among women in lower-income groups. In low- and middle-income countries, many women do not follow World Health Organization (WHO) recommendations to initiate breastfeeding within the first hour after birth. This is an update of a Cochrane Review, first published in 2005. To identify and describe health promotion activities intended to increase the initiation rate of breastfeeding.To evaluate the effectiveness of different types of breastfeeding promotion activities, in terms of changing the number of women who initiate breastfeeding.To evaluate the effectiveness of different types of breastfeeding promotion activities, in terms of changing the number of women who initiate breastfeeding early (within one hour after birth). We searched Cochrane Pregnancy and Childbirth's Trials Register (29 February 2016) and scanned reference lists of all articles obtained. Randomised controlled trials (RCTs), with or without blinding, of any breastfeeding promotion intervention in any population group, except women and infants with a specific health problem. Two review authors independently assessed trial reports for inclusion, extracted data and assessed trial quality. Discrepancies were resolved through discussion and a third review author was involved when necessary. We contacted investigators to obtain missing information. Twenty-eight trials involving 107,362 women in seven countries are included in this updated review. Five studies involving 3,124 women did not contribute outcome data and we excluded them from the analyses. The methodological quality of the included trials was mixed, with significant numbers of studies at high or unclear risk of bias due to: inadequate allocation concealment (N = 20); lack of blinding of outcome assessment (N = 20); incomplete outcome data (N = 19); selective reporting (N = 22) and bias from other potential sources (N = 17). Healthcare professional-led breastfeeding education and support versus standard care The studies pooled here compare professional health workers delivering breastfeeding education and support during the prenatal and postpartum periods with standard care. Interventions included promotion campaigns and counselling, and all took place in a formal setting. There was evidence from five trials involving 564 women for improved rates ofbreastfeeding initiation among women who received healthcare professional-led breastfeeding education and support (average risk ratio (RR) 1.43, 95% confidence interval (CI) 1.07 to 1.92; Tau² = 0.07, I² = 62%, low-quality evidence) compared to those women who received standard care. We downgraded evidence due to design limitations and heterogeneity. The outcome of early initiation of breastfeeding was not reported in the studies under this comparison. Non-healthcare professional-led breastfeeding education and support versus standard care There was evidence from eight trials of 5712 women for improved rates of breastfeeding initiation among women who received interventions from non-healthcare professional counsellors and support groups (average RR 1.22, 95% CI 1.06 to 1.40; Tau² = 0.02, I² = 86%, low-quality evidence) compared to women who received standard care. In three trials of 76,373 women, there was no clear difference between groups in terms of the number of women practicing early initiation of breastfeeding (average RR 1.70, 95% CI 0.98 to 2.95; Tau² = 0.18, I² = 78%, very low-quality evidence). We downgraded the evidence for a combination of design limitations, heterogeneity and imprecision (wide confidence intervals crossing the line of no effect). Other comparisonsOther comparisons in this review also looked at the rates of initiation of breastfeeding and there were no clear differences between groups for the following comparisons of combined healthcare professional-led education with peer support or community educator versus standard care (2 studies, 1371 women) or attention control (1 study, 237 women), breastfeeding education using multimedia (a self-help manual or a video) versus routine care (2 studies, 497 women); early mother-infant contact versus standard care (2 studies, 309 women); and community-based breastfeeding groups versus no breastfeeding groups (1 study, 18,603 women). None of these comparisons reported data on early initiation of breastfeeding. This review found low-quality evidence that healthcare professional-led breastfeeding education and non-healthcare professional-led counselling and peer support interventions can result in some improvements in the number of women beginning to breastfeed. The majority of the trials were conducted in the USA, among women on low incomes and who varied in ethnicity and feeding intention, thus limiting the generalisability of these results to other settings.Future studies would ideally be conducted in a range of low- and high-income settings, with data on breastfeeding rates over various timeframes, and explore the effectiveness of interventions that are initiated prior to conception or during pregnancy. These might include well-described interventions, including health education, early and continuing mother-infant contact, and initiatives to help mothers overcome societal barriers to breastfeeding, all with clearly defined outcome measures.

Comparative effectiveness research for the clinician researcher: a framework for making a methodological design choice.

PubMed

Williams, Cylie M; Skinner, Elizabeth H; James, Alicia M; Cook, Jill L; McPhail, Steven M; Haines, Terry P

2016-08-17

Comparative effectiveness research compares two active forms of treatment or usual care in comparison with usual care with an additional intervention element. These types of study are commonly conducted following a placebo or no active treatment trial. Research designs with a placebo or non-active treatment arm can be challenging for the clinician researcher when conducted within the healthcare environment with patients attending for treatment.A framework for conducting comparative effectiveness research is needed, particularly for interventions for which there are no strong regulatory requirements that must be met prior to their introduction into usual care. We argue for a broader use of comparative effectiveness research to achieve translatable real-world clinical research. These types of research design also affect the rapid uptake of evidence-based clinical practice within the healthcare setting.This framework includes questions to guide the clinician researcher into the most appropriate trial design to measure treatment effect. These questions include consideration given to current treatment provision during usual care, known treatment effectiveness, side effects of treatments, economic impact, and the setting in which the research is being undertaken.

Targeting Mitogen-activated Protein Kinase-activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts to Lead Small Molecule Inhibitors to Clinical Trials

PubMed Central

Fiore, Mario; Forli, Stefano; Manetti, Fabrizio

2015-01-01

The p38/MAPK-activated kinase 2 (MK2) pathway is involved in a series of pathological conditions (inflammation diseases and metastasis) and in the resistance mechanism to antitumor agents. None of the p38 inhibitors entered advanced clinical trials because of their unwanted systemic side effects. For this reason, MK2 was identified as an alternative target to block the pathway, but avoiding the side effects of p38 inhibition. However, ATP-competitive MK2 inhibitors suffered from low solubility, poor cell permeability, and scarce kinase selectivity. Fortunately, non-ATP-competitive inhibitors of MK2 have been already discovered that allowed circumventing the selectivity issue. These compounds showed the additional advantage to be effective at lower concentrations in comparison to the ATP-competitive inhibitors. Therefore, although the significant difficulties encountered during the development of these inhibitors, MK2 is still considered as an attractive target to treat inflammation and related diseases, to prevent tumor metastasis, and to increase tumor sensitivity to chemotherapeutics. PMID:26502061

ARDS following oesophagectomy: a comparison of two trials.

PubMed

Howells, Phillip A; Aldridge, Kerrie A; Parekh, Dhruv; Park, Daniel; Tucker, Olga; Dancer, Rachel C A; Gao, Fang; Perkins, Gavin D; Thickett, David R

2017-01-01

The Beta Agonist Lung Injury Trial-Prevention (BALTI-P) translational substudy and Vitamin D to Prevent Acute Lung Injury Following Oesophagectomy (VINDALOO) trials recruited patients undergoing oesophagectomy, 4 years apart. The acute respiratory distress syndrome (ARDS) rates were lower in the VINDALOO trial. We sought to identify changes between these two trials and identify risk factors for ARDS in oesophagectomy. There were data available from 61 patients in the BALTI-P substudy and 68 from VINDALOO. Databases were available for both trials; additional data were collected. Multivariate logistic regression was used to analyse risk factors for ARDS and postoperative complications in the cohorts combined. Logistic regression analysis showed active smoking was associated with an increase in ARDS (OR 3.91; 95% CI 1.33 to 11.5) and dihydropyridine use (OR 5.34;95% CI 1.56 to 18.3). Hospital length of stay was longer for those who took dihydropyridines (median 29 days (IQR 17-42) vs 13 days (IQR 10-18), P=0.0007) or were diabetic (median 25 days (IQR 14-39) vs 13 (IQR 10-19), P=0.023) but not for current smokers (median in never/ex-smokers 13 (IQR 10-23) vs current smokers 15 (IQR 11-20), P=0.73). Smoking cessation trials should be promoted. Dihydropyridine effects perioperatively require further clinical and mechanistic evaluation. Patients undergoing oesophagectomy are a useful model for studying perioperative ARDS.

ADCS Prevention Instrument Project: assessment of instrumental activities of daily living for community-dwelling elderly individuals in dementia prevention clinical trials.

PubMed

Galasko, Douglas; Bennett, David A; Sano, Mary; Marson, Daniel; Kaye, Jeff; Edland, Steven D

2006-01-01

In primary prevention trials for Alzheimer disease, the inception cohort typically has normal or minimally impaired complex activities of daily living (ADL). ADL change during a trial could trigger detailed evaluation or serve as an outcome measure. A brief, easily administered, and reliable ADL rating scale would assist prevention studies. To develop an ADL scale for prevention trials that allows self-rating or completion by informants. The Activities of Daily Living-Prevention Instrument (ADL-PI) was developed, comprising 15 ADL and 5 physical function questions. Six hundred forty-four elderly subjects participating in the Prevention Instrument Project completed a self-rated version of the ADL-PI, and informants for 632 subjects completed an informant version. Informants also completed a Mild Cognitive Impairment (MCI) ADL questionnaire to allow comparisons. Subjects performed well on all ADL scales at baseline. Completion of the ADL-PI questionnaires at home or in-clinic yielded comparable information. Scores from baseline to 3 months had good reliability. The ADL-PI, obtained from either self-report or informants, discriminated between subjects rated as CDR 0 and CDR 0.5. Subjects with worse baseline cognitive performance also had slightly worse ADL-PI scores. Preliminary analysis indicates that subjects who triggered cognitive evaluations had slightly lower baseline ADL-PI scores by both self and informant reports. The ADL-PI can be completed at home or in clinic, and has adequate reliability. The utility of self-administered and informant versions and predictive value of reported deficits requires further follow-up.

Meta-analysis of interventions for posttraumatic stress disorder and depression in adult survivors of mass violence in low- and middle-income countries.

PubMed

Morina, Nexhmedin; Malek, Mina; Nickerson, Angela; Bryant, Richard A

2017-08-01

Most survivors of mass violence live in low- and middle-income countries (LMICs). We conducted a meta-analysis of randomized controlled psychotherapy trials for adult posttraumatic stress disorder (PTSD) and/or depression in LMICs. We included 18 clinical trials (3,058 participants), in which 25 and 18 treatment arms measured symptoms of PTSD and depression, respectively. Active treatments for PTSD yielded a large aggregated pre-post effect size (g = 1.29; 95% CI = [0.99; 1.59]) and a small to medium effect size at posttreatment when compared to control conditions (g = 0.39; 95% CI = [0.24; 0.55]). Effect sizes were similar for pretreatment versus follow-up (g = 1.75; 95% CI = [1.17; 2.32]) and in comparison to waitlist at follow-up (g = 0.93; 95% CI = [0.56; 1.31]). Active treatments for depression produced large pre-post (g = 1.28; 95% CI = [0.96; 1.61]) and controlled effect sizes (posttreatment, comparison to control conditions, g = 0.86; 95% CI = [0.54; 1.18]). Our findings suggest that psychological interventions can effectively reduce symptoms of PTSD and depression in LMICs. Future research needs to focus on cost-effective interventions that are likely to be disseminated to the large numbers of war survivors in LMICs. © 2017 Wiley Periodicals, Inc.

The contribution of the androgen receptor (AR) in human spatial learning and memory: A study in women with complete androgen insensitivity syndrome (CAIS).

PubMed

Mueller, S C; Verwilst, T; Van Branteghem, A; T'Sjoen, G; Cools, M

2016-02-01

Few studies have examined the impact of androgen insensitivity on human spatial learning and memory. In the present study, we tested 11 women with complete androgen insensitivity syndrome (CAIS), a rare genetic disorder characterized by complete absence of AR activity, and compared their performance against 20 comparison males and 19 comparison females on a virtual analog of the Morris Water Maze task. The results replicated a main sex effect showing that men relative to women were faster in finding the hidden platform and had reduced heading error. Furthermore, findings indicated that mean performance of women with CAIS was between control women and control men, though the differences were not statistically significant. Effect size estimates (and corresponding confidence intervals) of spatial learning trials showed little difference between women with CAIS and control women but CAIS women differed from men, but not women, on two variables, latency to find the platform and first-move latency. No differences between groups were present during visible platform trials or the probe trial, a measure of spatial memory. Moreover, groups also did not differ on estimates of IQ and variability of performance. The findings are discussed in relation to androgen insensitivity in human spatial learning and memory. Copyright © 2015 Elsevier Inc. All rights reserved.

SisterTalk: final results of a culturally tailored cable television delivered weight control program for Black women

PubMed Central

2013-01-01

Background Obesity among Black women continues to exceed that of other women. Most weight loss programs created without reference to specific cultural contexts are less effective for Black than White women. Weight control approaches accessible to Black women and adapted to relevant cultural contexts are important for addressing this problem. This paper reports the final results of SisterTalk, the randomized controlled trial of a cable TV weight control program oriented toward Black women. Methods A five group design included a comparison group and a 2 × 2 factorial comparison of a) interactive vs. passive programming and b) telephone social support vs no telephone support, with 12 weekly initial cable TV programs followed by 4 monthly booster videos. At baseline, 3, 8, and 12 months post randomization, telephone and in person surveys were administered on diet, physical activity, and physical measurements of height and weight were taken to calculate body mass index (BMI). Analysis of variance (ANOVA) was used to examine differences over time, and between treatment and comparison groups. Dose variables reflecting use of the TV/video and written materials were also assessed. Results At 3 months, BMI, weight, and dietary fat were significantly lower and physical activity significantly higher among women exposed to the Cable TV intervention compared to the wait-list comparison group. Significant dietary fat differences were still observed at 8 and 12 month evaluations, but not BMI or physical activity differences. Main effects were not observed for interactive programming or enhanced social support at any time point. Within the intervention group, higher watching of the TV series and higher reading of educational materials were both (separately) associated with significantly lower dietary fat. Conclusions Cable TV was an effective delivery channel to assist Black women with weight control, increasing physical activity and decreasing dietary fat during an initial intervention period, but only dietary changes persisted Enhanced social support and the ability to interact with others during the show were not effective complementary intervention components as conducted in this trial. Future research to strengthen the ability of this approach to achieve long term effects may offer even more promising outcomes. PMID:24373253

Repetitive peripheral magnetic stimulation for activities of daily living and functional ability in people after stroke.

PubMed

Momosaki, Ryo; Yamada, Naoki; Ota, Erika; Abo, Masahiro

2017-06-23

Repetitive peripheral magnetic stimulation (rPMS) is a form of therapy that creates painless stimulation of deep muscle structures to improve motor function in people with physical impairment from brain or nerve disorders. Use of rPMS for people after stroke has been identified as a feasible approach to improve activities of daily living and functional ability. However, no systematic reviews have assessed the findings of available trials. The effect and safety of this intervention for people after stroke currently remain uncertain. To assess the effect of rPMS for improving activities of daily living and functional ability in people after stroke. We searched the Cochrane Stroke Group Trials Register (August 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (August 2016), MEDLINE Ovid (November 2016), Embase Ovid (August 2016), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) in Ebsco (August 2016), PsycINFO Ovid (August 2016), the Allied and Complementary Medicine Database (AMED) Ovid (August 2016), Occupational Therapy Systematic Evaluation of Evidence (OTseeker) (August 2016), the Physiotherapy Evidence Database (PEDro) (October 2016), and ICHUSHI Web (October 2016). We also searched five ongoing trial registries, screened reference lists, and contacted experts in the field. We placed no restrictions on the language or date of publication when searching the electronic databases. We included randomised controlled trials (RCTs) conducted to assess the therapeutic effect of rPMS for people after stroke. Comparisons eligible for inclusion were (1) active rPMS only compared with 'sham' rPMS (a very weak form of stimulation or a sound only); (2) active rPMS only compared with no intervention; (3) active rPMS plus rehabilitation compared with sham rPMS plus rehabilitation; and (4) active rPMS plus rehabilitation compared with rehabilitation only. Two review authors independently assessed studies for inclusion. The same review authors assessed methods and risk of bias and extracted data. We contacted trial authors to ask for unpublished information if necessary. We resolved all disagreements through discussion. We included three trials (two RCTs and one cross-over trial) involving 121 participants. Blinding of participants and physicians was well reported in all trials, and overall risk of bias was low. We found no clear effect of rPMS on activities of daily living at the end of treatment (mean difference (MD) -3.00, 95% confidence interval (CI) -16.35 to 10.35; low-quality evidence) and at the end of follow-up (MD -2.00, 95% CI -14.86 to 10.86; low-quality evidence). Investigators in one study with 63 participants observed no statistical difference in improvement of upper limb function at the end of treatment (MD 2.00, 95% CI -4.91 to 8.91) and at the end of follow-up (MD 4.00, 95% CI -2.92 to 10.92). One trial with 18 participants showed that rPMS treatment was not associated with improved muscle strength at the end of treatment (MD 3.00, 95% CI -2.44 to 8.44). Another study reported a significant decrease in spasticity of the elbow at the end of follow-up (MD -0.48, 95% CI -0.93 to -0.03). No studies provided information on lower limb function and death. Based on the GRADE approach, we judged the certainty of evidence related to the primary outcome as low owing to the small sample size of one study. Available trials provided inadequate evidence to permit any conclusions about routine use of rPMS for people after stroke. Additional trials with large sample sizes are needed to determine an appropriate rPMS protocol as well as long-term effects. We identified three ongoing trials and will include these trials in the next review update.

Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update.

PubMed

Bautista, Francisco; Fioravantti, Victoria; de Rojas, Teresa; Carceller, Fernando; Madero, Luis; Lassaletta, Alvaro; Moreno, Lucas

2017-11-01

Survival rates for patients with medulloblastoma have improved in the last decades but for those who relapse outcome is dismal and new approaches are needed. Emerging drugs have been tested in the last two decades within the context of phase I/II trials. In parallel, advances in genetic profiling have permitted to identify key molecular alterations for which new strategies are being developed. We performed a systematic review focused on the design and outcome of early-phase trials evaluating new agents in patients with relapsed medulloblastoma. PubMed, clinicaltrials.gov, and references from selected studies were screened to identify phase I/II studies with reported results between 2000 and 2015 including patients with medulloblastoma aged <18 years. A total of 718 studies were reviewed and 78 satisfied eligibility criteria. Of those, 69% were phase I; 31% phase II. Half evaluated conventional chemotherapeutics and 35% targeted agents. Overall, 662 patients with medulloblastoma/primitive neuroectodermal tumors were included. The study designs and the response assessments were heterogeneous, limiting the comparisons among trials and the correct identification of active drugs. Median (range) objective response rate (ORR) for patients with medulloblastoma in phase I/II studies was 0% (0-100) and 6.5% (0-50), respectively. Temozolomide containing regimens had a median ORR of 16.5% (0-100). Smoothened inhibitors trials had a median ORR of 8% (3-8). Novel drugs have shown limited activity against relapsed medulloblastoma. Temozolomide might serve as backbone for new combinations. Novel and more homogenous trial designs might facilitate the development of new drugs. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Inferior parietal and right frontal contributions to trial-by-trial adaptations of attention to memory.

PubMed

Kizilirmak, Jasmin M; Rösler, Frank; Bien, Siegfried; Khader, Patrick H

2015-07-21

The attention to memory theory (AtoM) proposes that the same brain regions might be involved in selective processing of perceived stimuli (selective attention) and memory representations (selective retrieval). Although this idea is compelling, given consistently found neural overlap between perceiving and remembering stimuli, recent comparisons brought evidence for overlap as well as considerable differences. Here, we present a paradigm that enables the investigation of the AtoM hypothesis from a novel perspective to gain further insight into the neural resources involved in AtoM. Selective attention in perception is often investigated as a control process that shows lingering effects on immediately following trials. Here, we employed a paradigm capable of modulating selective retrieval in a similarly dynamic manner as in such selective-attention paradigms by inducing trial-to-trial shifts between relevant and irrelevant memory representations as well as changes of the width of the internal focus on memory. We found evidence for an involvement of bilateral inferior parietal lobe and right inferior frontal gyrus in reorienting the attentional focus on previously accessed memory representations. Moreover, we could dissociate the right inferior from the parietal activation in separate contrasts, suggesting that the right inferior frontal gyrus plays a role in facilitating attentional reorienting to memory representations when competing representations have been activated in the preceding trial, potentially by resolving this competition. Our results support the AtoM theory, i.e. that ventral frontal and parietal regions are involved in automatic attentional reorienting in memory, and highlight the importance of further investigations of the overlap and differences between regions involved in internal (memory) and external (perceptual) attentional selection. Copyright © 2015 Elsevier B.V. All rights reserved.

Reporting of Telehealth-Delivered Dietary Intervention Trials in Chronic Disease: Systematic Review.

PubMed

Warner, Molly M; Kelly, Jaimon T; Reidlinger, Dianne P; Hoffmann, Tammy C; Campbell, Katrina L

2017-12-11

Telehealth-delivered dietary interventions are effective for chronic disease management and are an emerging area of clinical practice. However, to apply interventions from the research setting in clinical practice, health professionals need details of each intervention component. The aim of this study was to evaluate the completeness of intervention reporting in published dietary chronic disease management trials that used telehealth delivery methods. Eligible randomized controlled trial publications were identified through a systematic review. The completeness of reporting of experimental and comparison interventions was assessed by two independent assessors using the Template for Intervention Description and Replication (TIDieR) checklist that consists of 12 items including intervention rationale, materials used, procedures, providers, delivery mode, location, when and how much intervention delivered, intervention tailoring, intervention modifications, and fidelity. Where reporting was incomplete, further information was sought from additional published material and through email correspondence with trial authors. Within the 37 eligible trials, there were 49 experimental interventions and 37 comparison interventions. One trial reported every TIDieR item for their experimental intervention. No publications reported every item for the comparison intervention. For the experimental interventions, the most commonly reported items were location (96%), mode of delivery (98%), and rationale for the essential intervention elements (96%). Least reported items for experimental interventions were modifications (2%) and intervention material descriptions (39%) and where to access them (20%). Of the 37 authors, 14 responded with further information, and 8 could not be contacted. Many details of the experimental and comparison interventions in telehealth-delivered dietary chronic disease management trials are incompletely reported. This prevents accurate interpretation of trial results and implementation of effective interventions in clinical practice. ©Molly M Warner, Jaimon T Kelly, Dianne P Reidlinger, Tammy C Hoffmann, Katrina L Campbell. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.12.2017.

Exploring Mediators of Physical Activity in Young Adult Cancer Survivors: Evidence from a Randomized Trial of a Facebook-Based Physical Activity Intervention

PubMed Central

Tate, Deborah F.; Mayer, Deborah K.; Allicock, Marlyn; Cai, Jianwen

2015-01-01

Purpose: This study examined the effects of a physical activity (PA) intervention for young adult cancer survivors on changes in self-efficacy, social support, and self-monitoring and determined whether changes in these social cognitive theory constructs mediated the relationship between the intervention and changes in PA. Methods: A 12-week randomized trial compared a Facebook-based intervention (FITNET) aimed at increasing moderate-to-vigorous intensity PA to a Facebook-based self-help comparison group. Young adult cancer survivors (N=86, aged 21–39) were randomly assigned to one of the two groups. Self-report measures of PA and psychosocial variables were collected at baseline and after 12 weeks. Results: The FITNET group reported lower self-efficacy for sticking to exercise (mean change=−0.38; 95% CI: −0.62 to −0.12; p=0.025) and social support from friends on social networking websites (mean change=−0.47; 95% CI: −1.45 to 0.65; p=0.039) relative to the self-help comparison group over time. Changes in social support from friends on social networking websites partially mediated the intervention effects on moderate-to-vigorous PA (mean indirect effect=−22.4; 95% CI: −62.0 to −2.8) in the unexpected direction. Across both groups, social support from friends and self-monitoring were positively associated with changes in moderate-to-vigorous PA. Conclusion: The proposed mediators did not explain the positive effects of the FITNET intervention on mild PA. The lack of significant improvements in psychosocial constructs among FITNET participants may partly explain why the intervention did not increase moderate-to-vigorous PA relative to the self-help comparison group. Future PA interventions with young adult cancer survivors should examine targeting social support from friends and self-monitoring. PMID:25852972

A comparison of two non-thrust mobilization techniques applied to the C7 segment in patients with restricted and painful cervical rotation.

PubMed

Creighton, Doug; Gruca, Mark; Marsh, Douglas; Murphy, Nancy

2014-11-01

Cervical mobilization and manipulation have been shown to improve cervical range of motion and pain. Rotatory thrust manipulation applied to the lower cervical segments is associated with controversy and the potential for eliciting adverse reactions (AR). The purpose of this clinical trial was to describe two translatory non-thrust mobilization techniques and evaluate their effect on cervical pain, motion restriction, and whether any adverse effects were reported when applied to the C7 segment. This trial included 30 participants with painful and restricted cervical rotation. Participants were randomly assigned to receive one of the two mobilization techniques. Active cervical rotation and pain intensity measurements were recorded pre- and post-intervention. Within group comparisons were determined using the Wilcoxon signed-rank test and between group comparisons were analyzed using the Mann-Whitney U test. Significance was set at P = 0.05. Thirty participants were evaluated immediately after one of the two mobilization techniques was applied. There was a statistically significant difference (improvement) for active cervical rotation after application of the C7 facet distraction technique for both right (P = 0.022) and left (P = 0.022) rotation. Statistically significant improvement was also found for the C7 facet gliding technique for both right (P = 0.022) and left rotation (P = 0.020). Pain reduction was statistically significant for both right and left rotation after application of both techniques. Both mobilization techniques produced similar positive effects and one was not statistically superior to the other. A single application of both C7 mobilization techniques improved active cervical rotation, reduced perceived pain, and did not produce any AR in 30 patients with neck pain and movement limitation. These two non-thrust techniques may offer clinicians an additional safe and effective manual intervention for patients with limited and painful cervical rotation. A more robust experimental design is recommended to further examine these and similar cervical translatory mobilization techniques.

Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.

PubMed

Quintana, Daniel S; Westlye, Lars T; Alnæs, Dag; Rustan, Øyvind G; Kaufmann, Tobias; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

2016-07-01

It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12. Copyright © 2016 Elsevier Ltd. All rights reserved.

GRIN: “GRoup versus INdividual physiotherapy following lower limb intra-muscular Botulinum Toxin-A injections for ambulant children with cerebral palsy: an assessor-masked randomised comparison trial”: study protocol

PubMed Central

2014-01-01

Background Cerebral palsy is the most common cause of physical disability in childhood. Spasticity is a significant contributor to the secondary impairments impacting functional performance and participation. The most common lower limb spasticity management is focal intramuscular injections of Botulinum Toxin-Type A accompanied by individually-delivered (one on one) physiotherapy rehabilitation. With increasing emphasis on improving goal-directed functional activity and participation within a family-centred framework, it is timely to explore whether physiotherapy provided in a group could achieve comparable outcomes, encouraging providers to offer flexible models of physiotherapy delivery. This study aims to compare individual to group-based physiotherapy following intramuscular Botulinum Toxin-A injections to the lower limbs for ambulant children with cerebral palsy aged four to fourteen years. Methods/Design An assessor-masked, block randomised comparison trial will be conducted with random allocation to either group-based or individual physiotherapy. A sample size of 30 (15 in each study arm) will be recruited. Both groups will receive six hours of direct therapy following Botulinum Toxin-A injections in either an individual or group format with additional home programme activities (three exercises to be performed three times a week). Study groups will be compared at baseline (T1), then at 10 weeks (T2, efficacy) and 26 weeks (T3, retention) post Botulinum Toxin-A injections. Primary outcomes will be caregiver/s perception of and satisfaction with their child’s occupational performance goals (Canadian Occupational Performance Measure) and quality of gait (Edinburgh Visual Gait Score) with a range of secondary outcomes across domains of the International Classification of Disability, Functioning and Health. Discussion This paper outlines the study protocol including theoretical basis, study hypotheses and outcome measures for this assessor-masked, randomised comparison trial comparing group versus individual models of physiotherapy following intramuscular injections of Botulinum Toxin-A to the lower limbs for ambulant children with cerebral palsy. Trial registration ACTRN12611000454976 PMID:24502231

Effectiveness of a Group Support Lifestyle Modification (GSLiM) Programme among Obese Adults in Workplace: A Randomised Controlled Trial.

PubMed

Jamal, Siti Noraida; Moy, Foong Ming; Azmi Mohamed, Mohd Nahar; Mukhtar, Firdaus

2016-01-01

There was an increasing trend in the prevalence of obesity and its comorbidities over the past decades in Malaysia. Effective intervention for obesity remains limited. This study aimed to compare the effectiveness of a group based lifestyle modification programme amongst obese individuals with an existing dietary counseling programme. We recruited one hundred and ninety four overweight and obese (BMI>27.5 kg/m2) employees from a local university. They were randomly allocated to either Group Support Lifestyle Modification (GSLiM) (intervention)(n = 97) or dietary counseling (comparison)(n = 97). The GSLIM activities included self monitoring, cognitive-behaviour sessions, exercise as well as dietary change advocacy, which were conducted through seminars and group sessions over 24 weeks. The comparison group was given dietary counselling once in 12 weeks. Both groups were followed up for additional 12 weeks to check for intervention effect sustenance. Anthropometric and biochemical parameters were measured at baseline, 12, 24 and 36 weeks; while dietary intake, physical activities, psychological measures and quality of life measured at baseline, 24 and 36 weeks. Data analysis was conducted using ANOVA repeated measures with intention to treat principle. The participants were predominantly women with mean (standard deviation) age of 40.5 (9.3) years. A total of 19.6% of the participants in GSLiM achieved 6% weight loss compared to 4.1% in the comparison group (Risk Ratio 4.75; 95% CI: 1.68, 13.45). At 24 weeks, the retention rate was 83.5% for GSLiM and 82.5% for comparison group. GSLiM participants also achieved significant improvement in total weight self-efficacy score, negative emotions and physical discomfort subscales, MDPSS friend subscale and all domains in quality of life. Participants in the comparison group experienced reduction in negative self-thoughts. The GSLiM programme proved to be more effective in achieving targeted weight loss, improving weight self-efficacy, friend social support, and quality of life compared to dietary counseling. Iranian Registry of Clinical Trials IRCT201104056127N1.

The effects of the empowerment education program in older adults with total hip replacement surgery.

PubMed

Huang, Tzu-Ting; Sung, Chia-Chun; Wang, Woan-Shyuan; Wang, Bi-Hwa

2017-08-01

To measure the effectiveness of an education empowerment program on primary (self-efficacy and self-care competence) and secondary outcomes (Activities of Daily Life, mobility, depressive mood and quality of life) for older adults with total hip replacement surgery. Degenerative arthritis is a common and serious chronic illness that impacts the quality of life of older adults. As joints continue to degenerate and the hip damaged by arthritis, activities of daily life will be difficult to perform due to severe hip pain and joint stiffness. Therefore, hip replacement surgery should be considered and effective nursing care should be provided to improve the recovery of older adults. A prospective randomized control trial. A trial was conducted from September 2013 - May 2014 in two hospitals in northern Taiwan. 108 participants were random assigned to either the education empowerment group or in the comparison group. The researchers collected baseline data at admission and outcomes on the day of discharge, one month after and three months after the discharge. After the interventions, the education empowerment group participants demonstrated significantly higher self-care competence and self-efficacy and lower depressive inclinations compared with those in the comparison group. Participants in both groups significantly improved on activities of daily life, mobility and quality of life over the course of the interventions. This education empowerment intervention was very effective in enhancing participants' outcomes. Moreover, involving both older adults and their caregivers for the participation this program is recommended for a greater impact. © 2017 John Wiley & Sons Ltd.

A walking programme and a supervised exercise class versus usual physiotherapy for chronic low back pain: a single-blinded randomised controlled trial. (The Supervised Walking In comparison to Fitness Training for Back Pain (SWIFT) Trial)

PubMed Central

Hurley, Deirdre A; O'Donoghue, Grainne; Tully, Mark A; Moffett, Jennifer Klaber; van Mechelen, Willem; Daly, Leslie; Boreham, Colin AG; McDonough, Suzanne M

2009-01-01

Background Chronic low back pain (CLBP) is a persistent disabling condition with rising significant healthcare, social and economic costs. Current research supports the use of exercise-based treatment approaches that encourage people with CLBP to assume a physically active role in their recovery. While international clinical guidelines and systematic reviews for CLBP support supervised group exercise as an attractive first-line option for treating large numbers of CLBP patients at low cost, barriers to their delivery include space and time restrictions in healthcare settings and poor patient attendance. The European Clinical Guidelines have identified the need for research in the use of brief/minimal contact self-activation interventions that encourage participation in physical activity for CLBP. Walking may be an ideally suited form of individualized exercise prescription as it is easy to do, requires no special skills or facilities, and is achievable by virtually all ages with little risk of injury, but its effectiveness for LBP is unproven. Methods and design This study will be an assessor-blinded randomized controlled trial that will investigate the difference in clinical effectiveness and costs of an individualized walking programme and a supervised general exercise programme compared to usual physiotherapy, which will act as the control group, in people with chronic low back pain. A sample of 246 patients will be recruited in Dublin, Ireland through acute general hospital outpatient physiotherapy departments that provide treatment for people with CLBP. Patients will be randomly allocated to one of the three groups in a concealed manner. The main outcomes will be functional disability, pain, quality of life, fear avoidance, back beliefs, physical activity, satisfaction and costs, which will be evaluated at baseline, and 3, 6 and 12 months [follow-up by pre-paid postage]. Qualitative telephone interviews and focus groups will be embedded in the research design to obtain feedback about participants' experiences of the interventions and trial participation, and to inform interpretation of the quantitative data. Planned analysis will be by intention to treat (quantitative data) and thematic analysis (qualitative data) Discussion The trial will evaluate the effectiveness of a walking programme and a supervised general exercise programme compared to usual physiotherapy in people with CLBP. Trial registration Current controlled trial ISRCTN17592092 PMID:19573247

Evaluation of the acoustic coordinated reset (CR®) neuromodulation therapy for tinnitus: study protocol for a double-blind randomized placebo-controlled trial.

PubMed

Hoare, Derek J; Pierzycki, Robert H; Thomas, Holly; McAlpine, David; Hall, Deborah A

2013-07-10

Current theories of tinnitus assume that the phantom sound is generated either through increased spontaneous activity of neurons in the auditory brain, or through pathological temporal firing patterns of the spontaneous neuronal discharge, or a combination of both factors. With this in mind, Tass and colleagues recently tested a number of temporally patterned acoustic stimulation strategies in a proof of concept study. Potential therapeutic sound regimes were derived according to a paradigm assumed to disrupt hypersynchronous neuronal activity, and promote plasticity mechanisms that stabilize a state of asynchronous spontaneous activity. This would correspond to a permanent reduction of tinnitus. The proof of concept study, conducted in Germany, confirmed the safety of the acoustic stimuli for use in tinnitus, and exploratory results indicated modulation of tinnitus-related pathological synchronous activity with potential therapeutic benefit. The most effective stimulation paradigm is now in clinical use as a sound therapy device, the acoustic coordinated reset (CR®) neuromodulation (Adaptive Neuromodulation GmbH (ANM), Köln, Germany). To measure the efficacy of CR® neuromodulation, we devised a powered, two-center, randomized controlled trial (RCT) compliant with the reporting standards defined in the Consolidated Standards of Reporting Trials (CONSORT) Statement. The RCT design also addresses the recent call for international standards within the tinnitus community for high-quality clinical trials. The design uses a between-subjects comparison with minimized allocation of participants to treatment and placebo groups. A minimization approach was selected to ensure that the two groups are balanced with respect to age, gender, hearing, and baseline tinnitus severity. The protocol ensures double blinding, with crossover of the placebo group to receive the proprietary intervention after 12 weeks. The primary endpoints are the pre- and post-treatment measures that provide the primary measures of efficacy, namely a validated and sensitive questionnaire measure of the functional impact of tinnitus. The trial is also designed to capture secondary changes in tinnitus handicap, quality (pitch, loudness, bandwidth), and changes in tinnitus-related pathological synchronous brain activity using electroencephalography (EEG). This RCT was designed to provide a confident high-level estimate of the efficacy of sound therapy using CR® neuromodulation compared to a well-matched placebo intervention, and uniquely in terms of sound therapy, examine the physiological effects of the intervention against its putative mechanism of action. ClinicalTrials.gov, NCT01541969.

Effectiveness of Activity-Based Therapy in Comparison with Surface Spinal Stimulation in People with Traumatic Incomplete Spinal Cord Injury for Activation of Central Pattern Generator for Locomotion: Study Protocol for a 24-Week Randomized Controlled Trial.

PubMed

Bedi, Parneet Kaur; Arumugam, Narkeesh; Chhabra, Harvinder Singh

2018-06-01

A multi-centric randomized controlled trial to be conducted at two sites, department of phyhysiotherapypy, Punjabi University, Patiala and rehabilitation department, Indian Spinal Injury Centre, New Delhi, India. To determine the effectiveness of activity-based therapy in comparison with surface spinal stimulation (SSS) in traumatic incomplete spinal cord injury (SCI) with special reference to locomotion-a central pattern generator controlled function. A major goal for many patients after SCI is to regain the function of locomotion. It is crucial that rehabilitation strives to maximize locomotor ability and functional recovery after SCI. Experimental evidence of improvement in stepping and motor control after activity-based training in animal models and human SCI has been translated into clinical neuro-rehabilitation. Control group participants will undertake an intensive 24-week duration thrice weekly program of activity-based therapy. In addition to this the participants in experimental group will also receive a session of 45 minutes of SSS on thrice weekly basis. The primary analysis for our study will be at 24 weeks. Linear regression will be used to determine the mean between-group differences and 95% confidence interval for all continuous outcomes using baseline scores and group allocation as covariates. The primary outcome measure is improvement in the level of walking index for SCI-II. The secondary outcome measures are modified Ashworth scale, Penn spasm frequency score, spinal cord independence measure-III, SCI functional ambulation inventory, Hoffman's reflex, somatosensory evoked potential, and American Spinal Injury Association Impairment Scale scores. An insight into training-induced mechanisms will be of great importance to fine tune such combined treatments and vindicate their efficacy in restoration of locomotion and functional activities in individuals with SCI.

An international survey of physicians regarding clinical trials: a comparison between Kyoto University Hospital and Seoul National University Hospital

PubMed Central

2013-01-01

Background International clinical trials are now rapidly expanding into Asia. However, the proportion of global trials is higher in South Korea compared to Japan despite implementation of similar governmental support in both countries. The difference in clinical trial environment might influence the respective physicians’ attitudes and experience towards clinical trials. Therefore, we designed a questionnaire to explore how physicians conceive the issues surrounding clinical trials in both countries. Methods A questionnaire survey was conducted at Kyoto University Hospital (KUHP) and Seoul National University Hospital (SNUH) in 2008. The questionnaire consisted of 15 questions and 2 open-ended questions on broad key issues relating to clinical trials. Results The number of responders was 301 at KUHP and 398 at SNUH. Doctors with trial experience were 196 at KUHP and 150 at SNUH. Among them, 12% (24/196) at KUHP and 41% (61/150) at SUNH had global trial experience. Most respondents at both institutions viewed clinical trials favorably and thought that conducting clinical trials contributed to medical advances, which would ultimately lead to new and better treatments. The main reason raised as a hindrance to conducting clinical trials was the lack of personnel support and time. Doctors at both university hospitals thought that more clinical research coordinators were required to conduct clinical trials more efficiently. KUHP doctors were driven mainly by pure academic interest or for their desire to find new treatments, while obtaining credits for board certification and co-authorship on manuscripts also served as motivation factors for doctors at SNUH. Conclusions Our results revealed that there might be two different approaches to increase clinical trial activity. One is a social level approach to establish clinical trial infrastructure providing sufficient clinical research professionals. The other is an individual level approach that would provide incentives to encourage doctors to participate in and conduct clinical trials. PMID:24156760

Real-life efficacy and reliability of training a hearing aid.

PubMed

Keidser, Gitte; Alamudi, Karima

2013-09-01

Commercial trainable hearing aids (HA) (i.e., devices that for a period are adjusted by the user in different acoustic environments and that subsequently with changing environments automatically adapt to the user's preferred settings), are readily available; however, little information exists about the efficacy of training a HA. The purpose of this study was to investigate the efficacy and reliability of training a HA in everyday environments. The participants were 26 hearing-impaired volunteers with a median age of 79 years and an average pure-tone average of 53 dB HL. Test devices were commercial, multimemory, prototype devices that enabled training of the compression characteristics in four frequency bands and in six sound classes. Participants wore the National Acoustic Laboratories nonlinear fitting procedure version 2 prescription for 3 weeks and trained the devices from the prescribed response for 3 weeks, before comparing their trained response with the prescription for 2 weeks. The devices were reset to the prescription, and 19 participants repeated the training and comparison trials. During the comparison trial, participants made daily diary ratings of their satisfaction with the programs, and a structured interview was completed at the end of the comparison trial. The participants displayed different needs for changing the prescription, with more daily adjustments leading to training across more sound classes. Unreliable observations were obtained from 8 participants after each of the test and retest comparison trials. Of the 10 participants who made sufficient changes to the prescription during the first trial, 80% preferred their trained response. The 8 "low trainers" reported no preference, and also reported lower overall satisfaction with the device. Fewer adjustments were made during the repeat trial, resulting in less training. Significant correlations between trained variations were seen for 63% of 19 participants. Of the 10 participants who provided valid data after both comparison trials, those who trained the device consistently generally showed consistent preferences, and vice versa. For those who wanted a change to the prescription, training was mostly effective. Limited data on reliability showed reasonable consistency in training outcomes and preferences. Findings, in particular on reliability, should be verified in larger populations. A guideline on how to clinically manage training with clients is presented.

Neurofeedback as a nonpharmacological treatment for adults with attention-deficit/hyperactivity disorder (ADHD): study protocol for a randomized controlled trial.

PubMed

Mayer, Kerstin; Wyckoff, Sarah Nicole; Fallgatter, Andreas J; Ehlis, Ann-Christine; Strehl, Ute

2015-04-18

Neurofeedback has been applied effectively in various areas, especially in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). This study protocol is designed to investigate the effect of slow cortical potential (SCP) feedback and a new form of neurofeedback using near-infrared spectroscopy (NIRS) on symptomatology and neurophysiological parameters in an adult ADHD population. A comparison of SCP and NIRS feedback therapy methods has not been previously conducted and may yield valuable findings about alternative treatments for adult ADHD. The outcome of both neurofeedback techniques will be assessed over 30 treatment sessions and after a 6-month follow-up period, and then will be compared to a nonspecific biofeedback treatment. Furthermore, to investigate if treatment effects in this proof-of-principle study can be predicted by specific neurophysiological baseline parameters, regression models will be applied. Finally, a comparison with healthy controls will be conducted to evaluate deviant pretraining neurophysiological parameters, stability of assessment measures, and treatment outcome. To date, an investigation and comparison of SCP and NIRS feedback training to an active control has not been conducted; therefore, we hope to gain valuable insights in effects and differences of these types of treatment for ADHD in adults. This study is registered with the German Registry of Clinical Trials: DRKS00006767 , date of registration: 8 October 2014.

Comparison of disease activity measures for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis.

PubMed

Merkel, P A; Cuthbertson, D D; Hellmich, B; Hoffman, G S; Jayne, D R W; Kallenberg, C G M; Krischer, J P; Luqmani, R; Mahr, A D; Matteson, E L; Specks, U; Stone, J H

2009-01-01

Currently, several different instruments are used to measure disease activity and extent in clinical trials of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, leading to division among investigative groups and difficulty comparing study results. An exercise comparing six different vasculitis instruments was performed. A total of 10 experienced vasculitis investigators from 5 countries scored 20 cases in the literature of Wegener granulomatosis or microscopic polyangiitis using 6 disease assessment tools: the Birmingham Vasculitis Activity Score (BVAS), The BVAS for Wegener granulomatosis (BVAS/WG), BVAS 2003, a Physician Global Assessment (PGA), the Disease Extent Index (DEI) and the Five Factor Score (FFS). Five cases were rescored by all raters. Reliability of the measures was extremely high (intraclass correlations for the six measures all = 0.98). Within each instrument, there were no significant differences or outliers among the scores from the 10 investigators. Test/retest reliability was high for each measure: range = 0.77 to 0.95. The scores of the five acute activity measures correlated extremely well with one another. Currently available tools for measuring disease extent and activity in ANCA-associated vasculitis are highly correlated and reliable. These results provide investigators with confidence to compare different clinical trial data and helps form common ground as international research groups develop new, improved and universally accepted vasculitis disease assessment instruments.

Measuring the validity and reliability of the Apple Watch as a physical activity monitor.

PubMed

Zhang, Peng; Godin, Steven D; Owens, Matthew V

2018-04-04

This study aimed to investigate the validity and reliability of the energy expenditure (EE) estimation of Apple Watch among college students. Thirty college students completed two sets of three 10-minute treadmill walking and running trials while wearing three Apple Watches and being connected to indirect calorimetry. The walking trials were at speeds of 54, 80, and 107 m•min-1 while the running trials were at 134, 161, 188m•min-1. Energy expenditure comparisons were made using Two-way ANOVA with repeatedmeasures. Reliability was analyzed by Intraclass Correlation. There was no significant device x speed interactions (F (15, 696) = 1.113, p = 0.341) between the indirect calorimetry (criterion) and Apple Watch. The lowest Inter-Class Correlation (ICC) scores were 0.49 (95%CI) at 54 while the highest were 0.72 (95%CI) at 107 and 134 m•min-1. Apple Watch demonstrated a low to moderate validity and reliability on measuring EE.

A community-based multilevel intervention for smoking, physical activity and diet: short-term findings from the Community Interventions for Health programme in Hangzhou, China.

PubMed

Lv, Jun; Liu, Qing-Min; Ren, Yan-Jun; He, Ping-Ping; Wang, Sheng-Feng; Gao, Fang; Li, Li-Ming

2014-04-01

To assess the short-term impact of a comprehensive, community-based multilevel intervention on knowledge, beliefs and practices with respect to smoking, physical activity and diet in Hangzhou, China. A non-randomised, controlled, before-after quasi-experimental trial was conducted in two intervention areas and one comparison area. The intervention built on a socioecological framework and took place across four settings: neighbourhoods, schools, workplaces and community health centres. Two independent cross-sectional surveys of adults aged 18-64 years at baseline and a subsequent follow-up were conducted in 2008/2009 and 2011 in the intervention and comparison areas. A 2-year intervention programme was begun in mid-2009 and continued until mid-2011. A total of 2016 adults at baseline and 2016 adults at follow-up completed the survey. Over the 2-year intervention period, the intervention areas showed a statistically significant decline (25.2% vs 18.7%, p<0.001) in the prevalence of smoking compared with the comparison area (18.0% vs 16.4%, p=0.343). The proportion of individuals who had noticed anyone smoking in any of nine locations in the previous 30 days demonstrated a statistically significant decline in the intervention (78.9% vs 66.5%, p<0.001) and comparison (76.3% vs 66.5%, p<0.001) areas. The fruit and vegetable consumption score increased in a statistically significant manner in the intervention (24.84 vs 25.97, p=0.036) and comparison (24.25 vs 26.67, p<0.001) areas. The metabolic equivalent of physical activity increased from 1204 to 1386 (p=0.023) in the intervention areas compared with 918 to 924 in the comparison area (p=0.201). After a 2-year intervention, beneficial changes were noted in the intervention areas with respect to smoking and physical activity but not diet. A community-based multilevel intervention programme is feasible in urban China.

What is the strength of evidence for heart failure disease-management programs?

PubMed

Clark, Alexander M; Savard, Lori A; Thompson, David R

2009-07-28

Heart failure (HF) disease-management programs are increasingly common. However, some large and recent trials of programs have not reported positive findings. There have also been parallel recent advances in reporting standards and theory around complex nonpharmacological interventions. These developments compel reconsideration in this Viewpoint of how research into HF-management programs should be evaluated, the quality, specificity, and usefulness of this evidence, and the recommendations for future research. Addressing the main determinants of intervention effectiveness by using the PICO (Patient, Intervention, Comparison, and Outcome) approach and the recent CONSORT (Consolidated Standards of Reporting Trials) statement on nonpharmacological trials, we will argue that in both current trials and meta-analyses, interventions and comparisons are not sufficiently well described; that complex programs have been excessively oversimplified; and that potentially salient differences in programs, populations, and settings are not incorporated into analyses. In preference to more general meta-analyses of programs, adequate descriptions are first needed of populations, interventions, comparisons, and outcomes in past and future trials. This could be achieved via a systematic survey of study authors based on the CONSORT statement. These more detailed data on studies should be incorporated into future meta-analyses of comparable trials and used with other techniques such as patient-based outcomes data and meta-regression. Although trials and meta-analyses continue to have potential to generate useful evidence, a more specific evidence base is needed to support the development of effective programs for different populations and settings.

Financial incentive strategies for maintenance of weight loss: results from an internet-based randomized controlled trial.

PubMed

Yancy, William S; Shaw, Pamela A; Wesby, Lisa; Hilbert, Victoria; Yang, Lin; Zhu, Jingsan; Troxel, Andrea; Huffman, David; Foster, Gary D; Wojtanowski, Alexis C; Volpp, Kevin G

2018-05-25

Financial incentives can improve initial weight loss; we examined whether financial incentives can improve weight loss maintenance. Participants aged 30-80 years who lost at least 5 kg during the first 4-6 months in a nationally available commercial weight loss program were recruited via the internet into a three-arm randomized trial of two types of financial incentives versus active control during months 1-6 (Phase I) followed by passive monitoring during months 7-12 (Phase II). Interventions were daily self-weighing and text messaging feedback alone (control) or combined with a lottery-based incentive or a direct incentive. The primary outcome was weight change 6 months after initial weight loss. Secondary outcomes included weight change 12 months after initial weight loss (6 months after cessation of maintenance intervention), and self-reported physical activity and eating behaviors. Of 191 participants randomized, the mean age was 49.0 (SD = 10.5) years and weight loss prior to randomization was 11.4 (4.7) kg; 92% were women and 89% were White. Mean weight changes during the next 6 months (Phase I) were: lottery -3.0 (5.8) kg; direct -2.8 (5.8) kg; and control -1.4 (5.8) kg (all pairwise comparisons p > 0.1). Weight changes through the end of 12 months post-weight loss (Phase II) were: lottery -1.8 (10.5) kg; direct -0.7 (10.7) kg; and control -0.3 (9.4) kg (all pairwise comparisons p > 0.1). The percentages of participants who maintained their weight loss (defined as gaining ≤1.36 kg) were: lottery 79%, direct 76%, and control 67% at 6 months and lottery 66%, direct 62%, and control 59% at 12 months (all pairwise comparisons p > 0.1). At 6 and 12 months after initial weight loss, changes in self-reported physical activity or eating behaviors did not differ across arms. Compared with the active control of daily texting based on daily home weighing, lottery-based and direct monetary incentives provided no additional benefit for weight loss maintenance.

Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials.

PubMed

Roth, Daniel E; Leung, Michael; Mesfin, Elnathan; Qamar, Huma; Watterworth, Jessica; Papp, Eszter

2017-11-29

Objectives  To estimate the effects of vitamin D supplementation during pregnancy on 11 maternal and 27 neonatal/infant outcomes; to determine frequencies at which trial outcome data were missing, unreported, or inconsistently reported; and to project the potential contributions of registered ongoing or planned trials. Design  Systematic review and meta-analysis of randomised controlled trials; systematic review of registered but unpublished trials. Data sources  Medline, Embase, PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to September 2017; manual searches of reference lists of systematic reviews identified in the electronic search; and online trial registries for unpublished, ongoing, or planned trials. Eligibility criteria for study selection  Trials of prenatal vitamin D supplementation with randomised allocation and control groups administered placebo, no vitamin D, or vitamin D ≤600 IU/day (or its equivalent), and published in a peer reviewed journal. Results  43 trials (8406 participants) were eligible for meta-analyses. Median sample size was 133 participants. Vitamin D increased maternal/cord serum concentration of 25-hydroxyvitamin D, but the dose-response effect was weak. Maternal clinical outcomes were rarely ascertained or reported, but available data did not provide evidence of benefits. Overall, vitamin D increased mean birth weight of 58.33 g (95% confidence interval 18.88 g to 97.78 g; 37 comparisons) and reduced the risk of small for gestational age births (risk ratio 0.60, 95% confidence interval 0.40 to 0.90; seven comparisons), but findings were not robust in sensitivity and subgroup analyses. There was no effect on preterm birth (1.0, 0.77 to 1.30; 15 comparisons). There was strong evidence that prenatal vitamin D reduced the risk of offspring wheeze by age 3 years (0.81, 0.67 to 0.98; two comparisons). For most outcomes, meta-analyses included data from a minority of trials. Only eight of 43 trials (19%) had an overall low risk of bias. Thirty five planned/ongoing randomised controlled trials could contribute 12 530 additional participants to future reviews. Conclusions  Most trials on prenatal vitamin D published by September 2017 were small and of low quality. The evidence to date seems insufficient to guide clinical or policy recommendations. Future trials should be designed and powered to examine clinical endpoints, including maternal conditions related to pregnancy (such as pre-eclampsia), infant growth, and respiratory outcomes. Systematic review registration  PROSPERO CRD42016051292. 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.

A systematic review of evidence for the effectiveness of practitioner-based complementary and alternative therapies in the management of rheumatic diseases: osteoarthritis.

PubMed

Macfarlane, Gary J; Paudyal, Priya; Doherty, Michael; Ernst, Edzard; Lewith, George; MacPherson, Hugh; Sim, Julius; Jones, Gareth T

2012-12-01

To critically review the evidence on the efficacy and effectiveness of practitioner-based complementary therapies for patients with osteoarthritis. We excluded t'ai chi and acupuncture, which have been the subject of recent reviews. Randomized controlled trials, published in English up to May 2011, were identified using systematic searches of bibliographic databases and searching of reference lists. Information was extracted on outcomes, statistical significance in comparison with alternative treatments and reported side effects. The methodological quality of the identified studies was determined using the Jadad scoring system. Outcomes considered were pain and patient global assessment. In all, 16 eligible trials were identified covering 12 therapies. Overall, there was no good evidence of the effectiveness of any of the therapies in relation to pain or global health improvement/quality of life because most therapies only had a single randomized controlled trial. Where positive results were reported, they were often comparing an active intervention with no intervention. Therapies with multiple trials either provided null (biofeedback) or inconsistent results (magnet therapy), or the trials available scored poorly for quality (chiropractic). There were few adverse events reported in the trials. There is not sufficient evidence to recommend any of the practitioner-based complementary therapies considered here for the management of OA, but neither is there sufficient evidence to conclude that they are not effective or efficacious.

A noninferiority confirmatory trial of prasugrel versus clopidogrel in Japanese patients with non-cardioembolic stroke: rationale and study design for a randomized controlled trial - PRASTRO-I trial.

PubMed

Nagao, Takehiko; Toyoda, Kazunori; Kitagawa, Kazuo; Kitazono, Takanari; Yamagami, Hiroshi; Uchiyama, Shinichiro; Tanahashi, Norio; Matsumoto, Masayasu; Minematsu, Kazuo; Nagata, Izumi; Nishikawa, Masakatsu; Nanto, Shinsuke; Abe, Kenji; Ikeda, Yasuo; Ogawa, Akira

2018-04-01

This comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO)-I trial investigates the noninferiority of prasugrel to clopidogrel sulfate in the prevention of recurrence of primary events (ischemic stroke, myocardial infarction, and death from other vascular causes), and the long-term safety of prasugrel in Japanese patients with non-cardioembolic stroke. This was an active-controlled, randomized, double-blind, double-dummy, parallel-group study conducted between July 2011 and March 2016 at multiple centers around Japan. Patients had to meet eligibility criteria before receiving 3.75 mg prasugrel or 75 mg clopidogrel orally once daily for a period of 96-104 weeks. A total of 3747 patients were included in this trial; 1598 in the 3.75 mg prasugrel group and 1551 in the 75 mg clopidogrel group completed the study. During the study period, 287 (15.2%) patients in the prasugrel group and 311 (16.7%) in the clopidogrel group discontinued treatment. Baseline characteristics, safety, and efficacy results are forthcoming and will be published separately. This article presents the study design and rationale for a trial investigating the noninferiority of prasugrel to clopidogrel sulfate with regards to the inhibitory effect on primary events in patients with non-cardioembolic stroke.

Minimal olfactory perception during sleep: why odor alarms will not work for humans.

PubMed

Carskadon, Mary A; Herz, Rachel S

2004-05-01

To examine olfactory arousal threshold during sleep in comparison to an auditory tone. On night 1, participants rated odor intensity when awake and experienced olfactory stimuli during stage 1 sleep. Night 2 involved stage 2, stage 4, and rapid-eye-movement (REM) sleep trials using the "staircase" threshold-detection method. Electroencephalogram, electrooculogram, electromyogram, electrocardiogram, and respiration were recorded along with behavioral response. An 800-Hz tone was given on trials when odors failed to arouse. Participants slept in individual rooms. Stimulus-delivery systems were operated from a separate room, where an experimenter observed physiologic recordings and behavioral responses. Three healthy men and 3 women aged 20 to 25 years (mean, 22 years). Two odorants, peppermint and pyridine, at 4 concentrations were presented through nasal cannulas using an air-dilution olfactometer. Tones were played over a speaker. Behavioral (button press and oral) responses, electroencephalographic activation, and changes in breathing and heart rate were assessed. Participants responded to odors on 92% of stage 1 sleep trials. Peppermint was ineffective in stages 2, 4, and REM sleep. Pyridine produced behavioral threshold on 45% of stage 2 trials, none in stage 4, and one third of REM sleep trials. Tones were effective on at least 75% of trials. Heart rate increased significantly only following behavioral responses to odors or tones across sleep stages. The data indicate that human olfaction is not reliably capable of alerting a sleeper.

Eye movements reflect and shape strategies in fraction comparison.

PubMed

Ischebeck, Anja; Weilharter, Marina; Körner, Christof

2016-01-01

The comparison of fractions is a difficult task that can often be facilitated by separately comparing components (numerators and denominators) of the fractions--that is, by applying so-called component-based strategies. The usefulness of such strategies depends on the type of fraction pair to be compared. We investigated the temporal organization and the flexibility of strategy deployment in fraction comparison by evaluating sequences of eye movements in 20 young adults. We found that component-based strategies could account for the response times and the overall number of fixations observed for the different fraction pairs. The analysis of eye movement sequences showed that the initial eye movements in a trial were characterized by stereotypical scanning patterns indicative of an exploratory phase that served to establish the kind of fraction pair presented. Eye movements that followed this phase adapted to the particular type of fraction pair and indicated the deployment of specific comparison strategies. These results demonstrate that participants employ eye movements systematically to support strategy use in fraction comparison. Participants showed a remarkable flexibility to adapt to the most efficient strategy on a trial-by-trial basis. Our results confirm the value of eye movement measurements in the exploration of strategic adaptation in complex tasks.

Intertrial Sources of Stimulus Control and Delayed Matching-to-Sample Performance in Humans

ERIC Educational Resources Information Center

Williams, Dean C.; Johnston, Mark D.; Saunders, Kathryn J.

2006-01-01

Two experiments compared delayed matching-to-sample (DMTS) accuracy under 2 procedures in adults with mental retardation. In the trial-unique procedure, every trial in a session contained different stimuli. Thus, comparison stimuli that were correct on one trial were never incorrect on other trials in that session (or vice versa). In the 2-sample…

Comparison of accelerometer cut points for predicting activity intensity in youth.

PubMed

Trost, Stewart G; Loprinzi, Paul D; Moore, Rebecca; Pfeiffer, Karin A

2011-07-01

The absence of comparative validity studies has prevented researchers from reaching consensus regarding the application of intensity-related accelerometer cut points for children and adolescents. This study aimed to evaluate the classification accuracy of five sets of independently developed ActiGraph cut points using energy expenditure, measured by indirect calorimetry, as a criterion reference standard. A total of 206 participants between the ages of 5 and 15 yr completed 12 standardized activity trials. Trials consisted of sedentary activities (lying down, writing, computer game), lifestyle activities (sweeping, laundry, throw and catch, aerobics, basketball), and ambulatory activities (comfortable walk, brisk walk, brisk treadmill walk, running). During each trial, participants wore an ActiGraph GT1M, and V˙O2 was measured breath-by-breath using the Oxycon Mobile portable metabolic system. Physical activity intensity was estimated using five independently developed cut points: Freedson/Trost (FT), Puyau (PU), Treuth (TR), Mattocks (MT), and Evenson (EV). Classification accuracy was evaluated via weighted κ statistics and area under the receiver operating characteristic curve (ROC-AUC). Across all four intensity levels, the EV (κ=0.68) and FT (κ=0.66) cut points exhibited significantly better agreement than TR (κ=0.62), MT (κ=0.54), and PU (κ=0.36). The EV and FT cut points exhibited significantly better classification accuracy for moderate- to vigorous-intensity physical activity (ROC-AUC=0.90) than TR, PU, or MT cut points (ROC-AUC=0.77-0.85). Only the EV cut points provided acceptable classification accuracy for all four levels of physical activity intensity and performed well among children of all ages. The widely applied sedentary cut point of 100 counts per minute exhibited excellent classification accuracy (ROC-AUC=0.90). On the basis of these findings, we recommend that researchers use the EV ActiGraph cut points to estimate time spent in sedentary, light-, moderate-, and vigorous-intensity activity in children and adolescents.

Reduced servo-control of fatigued human finger extensor and flexor muscles.

PubMed Central

Hagbarth, K E; Bongiovanni, L G; Nordin, M

1995-01-01

1. In healthy human subjects holding the index finger semi-extended at the metacarpophalangeal joint against a moderate load, electromyographic (EMG) activity was recorded from the finger extensor and flexor muscles during different stages of muscle fatigue. The aim was to study the effect of muscle fatigue on the level of background EMG activity and on the reflex responses to torque pulses causing sudden extensor unloadings. Paired comparisons were made between the averaged EMG and finger deflection responses under two conditions: (1) at a stage of fatigue (following a sustained co-contraction) when great effort was required to maintain the finger position, and (2) under non-fatigue conditions while the subject tried to produce similar background EMG levels to those in the corresponding fatigue trials. 2. Both the unloading reflex in the extensor and the concurrent stretch reflex in the flexor were significantly less pronounced and had a longer latency in the fatigue trials. Consequently, the finger deflections had a larger amplitude and were arrested later in the fatigue trials. 3. It is concluded that--with avoidance of 'automatic gain compensation', i.e. reflex modifications attributable to differences in background EMG levels--the servo-like action of the unloading and stretch reflexes is reduced in fatigued finger extensor and flexor muscles. PMID:7562624

Modeling conflict and error in the medial frontal cortex.

PubMed

Mayer, Andrew R; Teshiba, Terri M; Franco, Alexandre R; Ling, Josef; Shane, Matthew S; Stephen, Julia M; Jung, Rex E

2012-12-01

Despite intensive study, the role of the dorsal medial frontal cortex (dMFC) in error monitoring and conflict processing remains actively debated. The current experiment manipulated conflict type (stimulus conflict only or stimulus and response selection conflict) and utilized a novel modeling approach to isolate error and conflict variance during a multimodal numeric Stroop task. Specifically, hemodynamic response functions resulting from two statistical models that either included or isolated variance arising from relatively few error trials were directly contrasted. Twenty-four participants completed the task while undergoing event-related functional magnetic resonance imaging on a 1.5-Tesla scanner. Response times monotonically increased based on the presence of pure stimulus or stimulus and response selection conflict. Functional results indicated that dMFC activity was present during trials requiring response selection and inhibition of competing motor responses, but absent during trials involving pure stimulus conflict. A comparison of the different statistical models suggested that relatively few error trials contributed to a disproportionate amount of variance (i.e., activity) throughout the dMFC, but particularly within the rostral anterior cingulate gyrus (rACC). Finally, functional connectivity analyses indicated that an empirically derived seed in the dorsal ACC/pre-SMA exhibited strong connectivity (i.e., positive correlation) with prefrontal and inferior parietal cortex but was anti-correlated with the default-mode network. An empirically derived seed from the rACC exhibited the opposite pattern, suggesting that sub-regions of the dMFC exhibit different connectivity patterns with other large scale networks implicated in internal mentations such as daydreaming (default-mode) versus the execution of top-down attentional control (fronto-parietal). Copyright © 2011 Wiley Periodicals, Inc.

Clinical comparison and performance perspective of three aligning arch wires.

PubMed

Evans, T J; Jones, M L; Newcombe, R G

1998-07-01

To clinically evaluate three commonly used orthodontic tooth aligning arch wires: 016 x 022 inch active martensitic medium force nickel titanium, 016 x 022 inch graded force active martensitic nickel titanium, and 0.0155 inch multistrand stainless steel. A prospective randomized clinical trial. Measured serial study casts of dental arches for 112 assigned arch wires from 56 consecutive patients. Analysis based on completed records for 98 arch wires and 51 patients. A consecutive sample of 56 patients requiring both upper and lower fixed appliance therapy were randomly allocated two different arch wires from a possible three under trial. Good quality impressions were taken of the dental arches at the designated serial stages of alignment (start, T0; 4 weeks, T4; 8 weeks, T8). The resultant casts were measured on a Reflex Microscope to record the change in individual tooth alignment both in three and two dimensions (horizontal plane only). The measurement error was within acceptable limits (range, 0.05 to 0.09 mm) and showed no significant bias. ANOVA statistical models were fitted to the data to adjust for a number of variables. No significant difference in aligning capability (p > 0.05), in either two or three dimensions, was demonstrated between the three arch wires in the trial. Heat activated nickel titanium arch wires failed to demonstrate a better performance than the cheaper multistrand stainless steel wires in this randomized clinical trial. The failure to demonstrate in vivo superiority at the clinical level may be due to the confounding effects of large variations in individual metabolic response. Alternatively, it may be that in routine clinical practice NiTi-type wires are not sufficiently deformed to allow their full superelastic properties to come in to play during initial alignment.

Results of the first-in-human clinical trial for MB-102, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Debreczeny, Martin P.; Dowling, Thomas C.

2015-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated MB-102, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in progress. This clinical trial is the first in a series of trials necessary to obtain regulatory clearance from the FDA. We report herein the comparison of plasma pharmacokinetics between MB-102 and the known standard exogenous GFR agent Iohexol in healthy subjects with normal renal function. Post simultaneous administration of both agents, blood samples over a period of 12 hours were collected from each subject to assess pharmacokinetic parameters including GFR. Urine samples were collected over this same period to assess percent injected dose recovered in the urine. Results indicate MB-102 is a GFR agent in humans from the comparison to the standard agent.

Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials

PubMed Central

Dombrowski, S U; Knittle, K; Avenell, A; Araújo-Soares, V

2014-01-01

Objective To systematically review and describe currently available approaches to supporting maintenance of weight loss in obese adults and to assess the evidence for the effectiveness of these interventions. Design Systematic review with meta-analysis. Data sources Medline, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials. Study selection Studies were identified through to January 2014. Randomised trials of interventions to maintain weight loss provided to initially obese adults (aged ≥18) after weight loss of ≥5% body weight with long term (≥12 months) follow-up of weight change (main outcome) were included. Study appraisal and synthesis Potential studies were screened independently and in duplicate; study characteristics and outcomes were extracted. Meta-analyses were conducted to estimate the effects of interventions on weight loss maintenance with the inverse variance method and a random effects model. Results are presented as mean differences in weight change, with 95% confidence intervals. Results 45 trials involving 7788 individuals were included. Behavioural interventions focusing on both food intake and physical activity resulted in an average difference of −1.56 kg (95% confidence interval −2.27 to −0.86 kg; 25 comparisons, 2949 participants) in weight regain compared with controls at 12 months. Orlistat combined with behavioural interventions resulted in a −1.80 kg (−2.54 to −1.06; eight comparisons, 1738 participants) difference compared with placebo at 12 months. All orlistat studies reported higher frequencies of adverse gastrointestinal events in the experimental compared with placebo control groups. A dose-response relation for orlistat treatment was found, with 120 mg doses three times a day leading to greater weight loss maintenance (−2.34 kg, −3.03 to −1.65) compared with 60 mg and 30 mg three times a day (−0.70 kg, 95% confidence interval −1.92 to 0.52), P=0.02. Conclusions Behavioural interventions that deal with both diet and physical activity show small but significant benefits on weight loss maintenance. PMID:25134100

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial

PubMed Central

2013-01-01

Background Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. Methods/Design This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. Discussion This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. Trial registration NCT01695850 PMID:24180235

Predicting the effect of interactive video bikes on exercise adherence: An efficacy trial.

PubMed

Rhodes, Ryan E; Warburton, Darren E R; Bredin, Shannon S D

2009-12-01

Exercise games that employ video game technology are increasing in the marketplace but have received scant research attention despite their popularity. The purpose of this study was to evaluate the effect of videobike gaming on the constructs of the theory of planned behavior (TPB) and adherence in comparison to a cycling condition where participants listen to self-selected music. Participants were 29 inactive young men assigned randomly to experimental (n = 16) or comparison (n = 13) conditions. The recommended training regime consisted of moderate intensity activity (60-75% heart rate reserve), 3 days/week for 30 min/day for 6 weeks. At the end of the first session, participants were asked to complete TPB measures and these were subsequently measured 6 weeks later. Attendance was used as the measure of adherence. Results showed that affective attitude and adherence across the 6 weeks significantly favored the videobike condition over the comparison condition. Regression analyses suggested partial mediation of the effect of the videobike condition on adherence via affective attitude. This is the first study to provide evidence that interactive videobikes may improve adherence over traditional cycling because the activity produces higher affective attitudes. The results are promising for expanding to community-based evaluation.

Weight management for adolescents with intellectual and developmental disabilities: Rationale and design for an 18month randomized trial.

PubMed

Donnelly, J E; Ptomey, L T; Goetz, J R; Sullivan, D K; Gibson, C A; Greene, J L; Lee, R H; Mayo, M S; Honas, J J; Washburn, R A

2016-11-01

Adolescents with intellectual and developmental disabilities (IDD) are an underserved group in need of weight management. However, information regarding effective weight management for this group is limited, and is based primarily on results from small, non-powered, non-randomized trials that were not conducted in accordance with current weight management guidelines. Additionally, the comparative effectiveness of emerging dietary approaches, such as portion-controlled meals (PCMs) or program delivery strategies such as video chat using tablet computers have not been evaluated. Therefore, we will conduct an 18month trial to compare weight loss (6months) and maintenance (7-18months) in 123 overweight/obese adolescents with mild to moderate IDD, and a parent, randomized to a weight management intervention delivered remotely using FaceTime™ on an iPad using either a conventional meal plan diet (RD/CD) or a Stop Light diet enhanced with PCMs (RD/eSLD), or conventional diet delivered during face-to-face home visits (FTF/CD). This design will provide an adequately powered comparison of both diet (CD vs. eSLD) and delivery strategy (FTF vs. RD). Exploratory analyses will examine the influence of behavioral session attendance, compliance with recommendations for diet (energy intake), physical activity (min/day), self-monitoring of diet and physical activity, medications, and parental variables including diet quality, physical activity, baseline weight, weight change, and beliefs and attitudes regarding diet and physical activity on both weight loss and maintenance. We will also complete a cost and contingent valuation analysis to compare costs between RD and FTF delivery. Copyright © 2016. Published by Elsevier Inc.

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

Contrast water therapy and exercise induced muscle damage: a systematic review and meta-analysis.

PubMed

Bieuzen, François; Bleakley, Chris M; Costello, Joseph Thomas

2013-01-01

The aim of this systematic review was to examine the effect of Contrast Water Therapy (CWT) on recovery following exercise induced muscle damage. Controlled trials were identified from computerized literature searching and citation tracking performed up to February 2013. Eighteen trials met the inclusion criteria; all had a high risk of bias. Pooled data from 13 studies showed that CWT resulted in significantly greater improvements in muscle soreness at the five follow-up time points (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Pooled data also showed that CWT significantly reduced muscle strength loss at each follow-up time (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Despite comparing CWT to a large number of other recovery interventions, including cold water immersion, warm water immersion, compression, active recovery and stretching, there was little evidence for a superior treatment intervention. The current evidence base shows that CWT is superior to using passive recovery or rest after exercise; the magnitudes of these effects may be most relevant to an elite sporting population. There seems to be little difference in recovery outcome between CWT and other popular recovery interventions.

Contrast Water Therapy and Exercise Induced Muscle Damage: A Systematic Review and Meta-Analysis

PubMed Central

Bieuzen, François; Bleakley, Chris M.; Costello, Joseph Thomas

2013-01-01

The aim of this systematic review was to examine the effect of Contrast Water Therapy (CWT) on recovery following exercise induced muscle damage. Controlled trials were identified from computerized literature searching and citation tracking performed up to February 2013. Eighteen trials met the inclusion criteria; all had a high risk of bias. Pooled data from 13 studies showed that CWT resulted in significantly greater improvements in muscle soreness at the five follow-up time points (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Pooled data also showed that CWT significantly reduced muscle strength loss at each follow-up time (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Despite comparing CWT to a large number of other recovery interventions, including cold water immersion, warm water immersion, compression, active recovery and stretching, there was little evidence for a superior treatment intervention. The current evidence base shows that CWT is superior to using passive recovery or rest after exercise; the magnitudes of these effects may be most relevant to an elite sporting population. There seems to be little difference in recovery outcome between CWT and other popular recovery interventions. PMID:23626806

Differences in Funding Sources of Phase III Oncology Clinical Trials by Treatment Modality and Cancer Type.

PubMed

Jairam, Vikram; Yu, James B; Aneja, Sanjay; Wilson, Lynn D; Lloyd, Shane

2017-06-01

Given the limited resources available to conduct clinical trials, it is important to understand how trial sponsorship differs among different therapeutic modalities and cancer types and to consider the ramifications of these differences. We searched clinicaltrials.gov for a cross-sectional register of active, phase III, randomized controlled trials (RCTs) studying treatment-related endpoints such as survival and recurrence for the 24 most prevalent malignancies. We classified the RCTs into 7 categories of therapeutic modality: (1) chemotherapy/other cancer-directed drugs, (2) targeted therapy, (3) surgery, (4) radiation therapy (RT), (5) RT with other modalities, (6) multimodality therapy without RT, and (7) other. RCTs were categorized as being funded by one or more of the following groups: (1) government, (2) hospital/university, (3) industry, and (4) other. χ analysis was performed to detect differences in funding source distribution between modalities and cancer types. The percentage of multimodality trials (5%) and radiation RCTs (4%) funded by industry was less than that for chemotherapy (32%, P<0.01) or targeted therapy (48%, P<0.01). Trials studying targeted therapy were less likely to have hospital/university funding than any of the other modalities (P<0.01 in each comparison). Trials of chemotherapy were more likely to be funded by industry if they also studied targeted therapy (P<0.01). RCTs studying targeted therapies are more likely to be funded by industry than trials studying multimodality therapy or radiation. The impact of industry funding versus institutional or governmental sources of funding for cancer research is unclear and requires further study.

Autonomic Nervous Activity and Lipid Oxidation Postexercise with Capsaicin in the Humans

PubMed Central

Yeo, Nam Hwoeh; Kang, Sunghwun

2010-01-01

This study evaluated the synergistic effects of acute exercise with capsaicin (200mg) upon the restoration of cardiac autonomic functions and depolarization- repolarization interval as well as substrate oxidation. Nine healthy males [21.9(0.8) yrs] volunteered for this study. Cardiac autonomic activity, metabolic responses, and the ECG QT intervals were continuously measured during 5 min at rest and postexercise recovery after 30 min exercise at 50% VO2max on a stationary ergometer with placebo (ECON) or capsaicin intake (ECAP), and no exercise control (NCON) were randomized. Results indicated that the HF power reflecting parasympathetic activity significantly returned to the baseline much faster during ECAP than ECON trial during postexercise [122.1 (23.2) vs. 60.2 (11.7) %, p < 0.05]. The ECAP trial significantly decreased RQ [0.79(0.02) vs. 0.85 (0.03), p < 0.05] with significantly greater fat oxidation [69.3 (6.0) vs. 49.4 (10.8) %, p < 0.05] in comparison to NCON trial during 120 min postexercise recovery without any adverse effects on cardiac electrical stability as determined by trigger-averaged ECG QT interval analyses. We suggest that capsaicin before the exercise may contribute to the improvement of cardio-protective functions and metabolic responses as one of the beneficial supplements accelerating faster restoration of autonomic activity and enhanced lipolysis during postexercise recovery without any adverse effects on cardiac electrical stability. Key points Capsaicin before exercise may contribute to the improvement of cardio-protective functions as one of the beneficial supplements accelerating faster restoration of autonomic activity Capsaicin before exercise enhanced lipolysis during postexercise recovery period Capsaicin intake does not influence cardiac electrical stability during recovery period. PMID:24149693

Physical activity intervention for elderly patients with reduced physical performance after acute coronary syndrome (HULK study): rationale and design of a randomized clinical trial.

PubMed

Tonet, Elisabetta; Maietti, Elisa; Chiaranda, Giorgio; Vitali, Francesco; Serenelli, Matteo; Bugani, Giulia; Mazzoni, Gianni; Ruggiero, Rossella; Myers, Jonathan; Villani, Giovanni Quinto; Corvi, Ursula; Pasanisi, Giovanni; Biscaglia, Simone; Pavasini, Rita; Lucchi, Giulia Ricci; Sella, Gianluigi; Ferrari, Roberto; Volpato, Stefano; Campo, Gianluca; Grazzi, Giovanni

2018-05-21

Reduced physical performance and impaired mobility are common in elderly patients after acute coronary syndrome (ACS) and they represent independent risk factors for disability, morbidity, hospital readmission and mortality. Regular physical exercise represents a means for improving functional capacity. Nevertheless, its clinical benefit has been less investigated in elderly patients in the early phase after ACS. The HULK trial aims to investigate the clinical benefit of an early, tailored low-cost physical activity intervention in comparison to standard of care in elderly ACS patients with reduced physical performance. HULK is an investigator-initiated, prospective multicenter randomized controlled trial (NCT03021044). After successful management of the ACS acute phase and uneventful first 1 month, elderly (≥70 years) patients showing reduced physical performance are randomized (1:1 ratio) to either standard of care or physical activity intervention. Reduced physical performance is defined as a short physical performance battery (SPPB) score of 4-9. The early, tailored, low-cost physical intervention includes 4 sessions of physical activity with a supervisor and an home-based program of physical exercise. The chosen primary endpoint is the 6-month SPPB value. Secondary endpoints briefly include quality of life, on-treatment platelet reactivity, some laboratory data and clinical adverse events. To demonstrate an increase of at least one SPPB point in the experimental arm, a sample size of 226 patients is needed. The HULK study will test the hypothesis that an early, tailored low-cost physical activity intervention improves physical performance, quality of life, frailty status and outcome in elderly ACS patients with reduced physical performance. Clinicaltrials.gov, identifier NCT03021044 , first posted January, 13th 2017.

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer.

PubMed

Hamdy, Freddie C; Donovan, Jenny L; Lane, J Athene; Mason, Malcolm; Metcalfe, Chris; Holding, Peter; Davis, Michael; Peters, Tim J; Turner, Emma L; Martin, Richard M; Oxley, Jon; Robinson, Mary; Staffurth, John; Walsh, Eleanor; Bollina, Prasad; Catto, James; Doble, Andrew; Doherty, Alan; Gillatt, David; Kockelbergh, Roger; Kynaston, Howard; Paul, Alan; Powell, Philip; Prescott, Stephen; Rosario, Derek J; Rowe, Edward; Neal, David E

2016-10-13

The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

What Individuals in Recovery Need to Know About Wellness

MedlinePlus

... Prevalence of the metabolic syndrome in patients with schizophrenia: Baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES ...

Focus on Alectinib and Competitor Compounds for Second-Line Therapy in ALK-Rearranged NSCLC

PubMed Central

Tran, Phu N.; Klempner, Samuel J.

2016-01-01

The management of anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) exemplifies the potential of a precision medicine approach to cancer care. The ALK inhibitor crizotinib has led to improved outcomes in the first- and second-line setting; however, toxicities, intracranial activity, and acquired resistance necessitated the advent of later generation ALK inhibitors. A large portion of acquired resistance to ALK inhibitors is caused by secondary mutations in the ALK kinase domain. Alectinib is a second-generation ALK inhibitor capable of overcoming multiple crizotinib-resistant ALK mutations and has demonstrated improved outcomes after crizotinib failure. Favorable toxicity profile and improved intracranial activity have spurred ongoing front-line trials and comparisons to other ALK inhibitors. However, important questions regarding comparability to competitor compounds, acquired alectinib resistance, and ALK inhibitor sequencing remain. Here, we review the key clinical data supporting alectinib in the second-line therapy of ALK+ NSCLC and provide context in comparison to other ALK inhibitors in development. PMID:27965961

Focus on Alectinib and Competitor Compounds for Second-Line Therapy in ALK-Rearranged NSCLC.

PubMed

Tran, Phu N; Klempner, Samuel J

2016-01-01

The management of anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) exemplifies the potential of a precision medicine approach to cancer care. The ALK inhibitor crizotinib has led to improved outcomes in the first- and second-line setting; however, toxicities, intracranial activity, and acquired resistance necessitated the advent of later generation ALK inhibitors. A large portion of acquired resistance to ALK inhibitors is caused by secondary mutations in the ALK kinase domain. Alectinib is a second-generation ALK inhibitor capable of overcoming multiple crizotinib-resistant ALK mutations and has demonstrated improved outcomes after crizotinib failure. Favorable toxicity profile and improved intracranial activity have spurred ongoing front-line trials and comparisons to other ALK inhibitors. However, important questions regarding comparability to competitor compounds, acquired alectinib resistance, and ALK inhibitor sequencing remain. Here, we review the key clinical data supporting alectinib in the second-line therapy of ALK+ NSCLC and provide context in comparison to other ALK inhibitors in development.

Neratinib for the treatment of breast cancer.

PubMed

Prové, Annemie; Dirix, Luc

2016-10-03

Neratinib is an orally available, pan-HER inhibitor with clinical activity in patients with HER2-amplified and HER2-mutated breast cancer. Areas Covered. A summary of publically available and relevant clinical data on neratinib. Expert Opinion. Neratinib (N) is clearly distinct from lapatinib (L), a difference based on its broad anti-HER effect, its covalent target binding and its toxicity profile. The main toxicity of neratinib is gastro-intestinal and is essentially limited to diarrhea. Although not directly compared with single agent lapatinib, skin toxicity is much less pronounced with N. The direct clinical comparison of N-capecitabine versus L-capecitabine is the subject of the ongoing NALA-trial. In patients with advanced disease, neratinib has clinically relevant activity in patients with trastuzumab(T)-pretreated and unpretreated disease. In patients having completed one year of adjuvant trastuzumab, an additional year of neratinib further reduces the risk of recurrence of invasive disease. The activity of neratinib in HER2-mutated advanced disease is subject of ongoing clinical trials but preclinical and early clinical results are promising. Neratinib is a usefull drug and a valuable addition to the different anti-HER2-drugs avalaible for patients with HER2-overexpressing and HER2-mutated breast cancer.

Increasing Recreational Physical Activity in Patients With Chronic Low Back Pain: A Pragmatic Controlled Clinical Trial.

PubMed

Ben-Ami, Noa; Chodick, Gabriel; Mirovsky, Yigal; Pincus, Tamar; Shapiro, Yair

2017-02-01

Study Design Prospective, pragmatic, nonrandomized controlled clinical trial. Background Clinical guidelines recommend physical activity for the treatment of chronic low back pain. But engaging patients in physical activity has proven difficult. Known obstacles to physical activity include low self-efficacy and fear avoidance. Objectives This study tested the effectiveness of an enhanced transtheoretical model intervention (ETMI) aimed at increasing recreational physical activity in patients with chronic low back pain, in comparison to usual physical therapy. Methods Patients (n = 220) referred to physical therapy for chronic low back pain were allocated to ETMI or to a control group. The ETMI was delivered by physical therapists and based on behavior-change principles, combined with increased reassurance, therapeutic alliance, and exposure to reduce fear avoidance. The primary outcome was back pain-related disability (Roland-Morris Disability Questionnaire). Secondary outcomes included pain intensity, mental and physical health, and levels of physical activity. Results Intention-to-treat analysis in 189 patients at 12 months indicated that patients in the ETMI group had significantly lower disability compared to usual physical therapy. The difference in mean change from baseline between the interventions was 2.7 points (95% confidence interval: 0.9, 4.5) on the Roland-Morris Disability Questionnaire. At 12 months, worst pain, physical activity, and physical health were all significantly better in patients receiving ETMI. The average number of sessions was 3.5 for the ETMI group and 5.1 for controls. Conclusion Targeting obstacles to physical activity with an intervention that includes components to address self-efficacy and fear avoidance appears to be more effective than usual physical therapy care in reducing long-term disability. Further research is needed to explore the mechanisms that impact outcomes in this intervention package. Level of Evidence Therapy, level 2b. Registered June 7, 2012 at ClinicalTrials.gov (NCT01631344). J Orthop Sports Phys Ther 2017;47(2):57-66. doi:10.2519/jospt.2017.7057.

Exercise interventions for smoking cessation.

PubMed

Ussher, Michael H; Taylor, Adrian; Faulkner, Guy

2012-01-18

Taking regular exercise may help people give up smoking by moderating nicotine withdrawal and cravings, and by helping to manage weight gain. To determine whether exercise-based interventions alone, or combined with a smoking cessation programme, are more effective than a smoking cessation intervention alone. In July 2011, we searched the Cochrane Tobacco Addiction Group Specialized Register for studies including the terms 'exercise' or 'physical activity'. We also searched MEDLINE, EMBASE, PsycINFO, Dissertation Abstracts and CINAHL using the terms 'exercise' or 'physical activity' and 'smoking cessation'. We included randomized trials which compared an exercise programme alone, or an exercise programme as an adjunct to a cessation programme, with a cessation programme, recruiting smokers or recent quitters, and with a follow up of six months or more. We extracted data on study characteristics and smoking outcomes. Because of differences in studies we summarized the results narratively, making no attempt at meta-analysis. We identified 15 trials, seven of which had fewer than 25 people in each treatment arm. They varied in the timing and intensity of the smoking cessation and exercise programmes. Three studies showed significantly higher abstinence rates in a physically active group versus a control group at end of treatment. One of these studies also showed a significant benefit for exercise versus control on abstinence at the three-month follow up and a benefit for exercise of borderline significance (p = 0.05) at the 12-month follow up. One study showed significantly higher abstinence rates for the exercise group versus a control group at the three-month follow up but not at the end of treatment or 12-month follow up. The other studies showed no significant effect for exercise on abstinence. Only one of the 15 trials offered evidence for exercise aiding smoking cessation at a 12-month follow up. All the other trials were too small to reliably exclude an effect of intervention, or included an exercise intervention which was insufficiently intense to achieve the desired level of exercise. Trials are needed with larger sample sizes, sufficiently intense interventions, equal contact control conditions, and measures of exercise adherence and change in physical activity in both exercise and comparison groups.

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.

Oral paracetamol versus oral ibuprofen for closure of haemodynamically significant patent ductus arteriosus in preterm neonates (<32 weeks): a blinded, randomised, active-controlled, non-inferiority trial

PubMed Central

Kumar, Ashutosh; Sundaram, Venkataseshan; Yadav, Rahul; Oleti, Tejo Pratap; Murki, Srinivas; Krishna, Arun; Sundaram, Mangalabharathi; Saini, Shiv Sajan; Dutta, Sourabh

2017-01-01

Introduction Haemodynamically significant patent ductus arteriosus (hsPDA) is a common cause of mortality and morbidity in preterm infants. Existing medical therapies with ibuprofen or indomethacin have multiple adverse effects. Hence, an alternative drug like paracetamol given through oral route with less side effects need to be tested in an appropriate study design with least risk of bias to arrive at a conclusion. Methods and analysis Multisite, randomised, active-controlled, non-inferiority design. The primary objective is to study the efficacy of oral paracetamol for closure of hsPDA in comparison to oral ibuprofen in preterm neonates of <32 weeks’ gestation. Randomisation web-based and allocation concealment would be done; the treating team, investigators, outcome assessors and laboratory personnel would be blinded from the intervention. Echocardiography images would be coded for independent review. Closure of PDA by the end of last dose of study drug or earlier would be the study endpoint. A sample size of 196 neonates would be enrolled with a non-inferiority margin of 15%. Both intention-to-treat and per-protocol analysis will be done to assess the effect of contamination and protocol violations in the primary outcome. Ethics and dissemination The trial would follow international code of ethics for clinical trial. The trial protocol was approved by the Institute Ethics Committee of all three centres. All serious adverse events would be reported in detail to the Institute Ethics Committee. A written informed consent would be obtained from one of the parents. No plan has been made for dissemination. Trial registration number CTRI/2014/08/004805. PMID:29637155

Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial.

PubMed

Verloop, Willemien L; Beeftink, Martine M A; Nap, Alex; Bots, Michiel L; Velthuis, Birgitta K; Appelman, Yolande E; Cramer, Maarten-Jan; Agema, Willem R P; Scholtens, Asbjorn M; Doevendans, Pieter A; Allaart, Cor P; Voskuil, Michiel

2013-12-01

Aim Increasing evidence suggests an important role for hyperactivation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal LVEF (HFNEF) and hypertension. Moreover, the level of renal sympathetic activation is directly related to the severity of heart failure. Since percutaneous renal denervation (pRDN) has been shown to be effective in modulating elevated SNS activity in patients with hypertension, it can be hypothesized that pRDN has a positive effect on HFNEF. The DIASTOLE trial will investigate whether renal sympathetic denervation influences parameters of HFNEF. Methods DIASTOLE is a multicentre, randomized controlled trial. Sixty patients, diagnosed with HFNEF and treated for hypertension, will be randomly allocated in a 1:1 ratio to undergo renal denervation on top of medical treatment (n = 30) or to maintain medical treatment alone (n = 30). The primary objective is to investigate the efficacy of pRDN by means of pulsed wave Doppler echocardiographic parameters. Secondary objectives include safety of pRDN and a comparison of changes in the following parameters after pRDN: LV mass, LV volume, LVEF, and left atrial volume as determined by magnetic resonance imaging. Also, MIBG (metaiodobenzylguanidine) uptake and washout, BNP levels, blood pressure, heart rate variability, exercise capacity, and quality of life will be assessed. Perspective DIASTOLE is a randomized controlled trial evaluating renal denervation as a treatment option for HFNEF. The results of the current trial will provide important information regarding the treatment of HFNEF, and therefore may have major impact on future therapeutic strategies. Trail registration NCT01583881.

The effects of methylphenidate on cerebral responses to conflict anticipation and unsigned prediction error in a stop-signal task.

PubMed

Manza, Peter; Hu, Sien; Ide, Jaime S; Farr, Olivia M; Zhang, Sheng; Leung, Hoi-Chung; Li, Chiang-shan R

2016-03-01

To adapt flexibly to a rapidly changing environment, humans must anticipate conflict and respond to surprising, unexpected events. To this end, the brain estimates upcoming conflict on the basis of prior experience and computes unsigned prediction error (UPE). Although much work implicates catecholamines in cognitive control, little is known about how pharmacological manipulation of catecholamines affects the neural processes underlying conflict anticipation and UPE computation. We addressed this issue by imaging 24 healthy young adults who received a 45 mg oral dose of methylphenidate (MPH) and 62 matched controls who did not receive MPH prior to performing the stop-signal task. We used a Bayesian Dynamic Belief Model to make trial-by-trial estimates of conflict and UPE during task performance. Replicating previous research, the control group showed anticipation-related activation in the presupplementary motor area and deactivation in the ventromedial prefrontal cortex and parahippocampal gyrus, as well as UPE-related activations in the dorsal anterior cingulate, insula, and inferior parietal lobule. In group comparison, MPH increased anticipation activity in the bilateral caudate head and decreased UPE activity in each of the aforementioned regions. These findings highlight distinct effects of catecholamines on the neural mechanisms underlying conflict anticipation and UPE, signals critical to learning and adaptive behavior. © The Author(s) 2016.

The effects of methylphenidate on cerebral responses to conflict anticipation and unsigned prediction error in a stop-signal task

PubMed Central

Manza, Peter; Hu, Sien; Ide, Jaime S; Farr, Olivia M; Zhang, Sheng; Leung, Hoi-Chung; Li, Chiang-shan R

2016-01-01

To adapt flexibly to a rapidly changing environment, humans must anticipate conflict and respond to surprising, unexpected events. To this end, the brain estimates upcoming conflict on the basis of prior experience and computes unsigned prediction error (UPE). Although much work implicates catecholamines in cognitive control, little is known about how pharmacological manipulation of catecholamines affects the neural processes underlying conflict anticipation and UPE computation. We addressed this issue by imaging 24 healthy young adults who received a 45 mg oral dose of methylphenidate (MPH) and 62 matched controls who did not receive MPH prior to performing the stop-signal task. We used a Bayesian Dynamic Belief Model to make trial-by-trial estimates of conflict and UPE during task performance. Replicating previous research, the control group showed anticipation-related activation in the presupplementary motor area and deactivation in the ventromedial prefrontal cortex and parahippocampal gyrus, as well as UPE-related activations in the dorsal anterior cingulate, insula, and inferior parietal lobule. In group comparison, MPH increased anticipation activity in the bilateral caudate head and decreased UPE activity in each of the aforementioned regions. These findings highlight distinct effects of catecholamines on the neural mechanisms underlying conflict anticipation and UPE, signals critical to learning and adaptive behavior. PMID:26755547

Neural correlates of reactive aggression in children with attention-deficit/hyperactivity disorder and comorbid disruptive behaviour disorders.

PubMed

Bubenzer-Busch, S; Herpertz-Dahlmann, B; Kuzmanovic, B; Gaber, T J; Helmbold, K; Ullisch, M G; Baurmann, D; Eickhoff, S B; Fink, G R; Zepf, F D

2016-04-01

Attention deficit hyperactivity disorder (ADHD) is often linked with impulsive and aggressive behaviour, indexed by high comorbidity rates between ADHD and disruptive behaviour disorders (DBD). The present study aimed to investigate underlying neural activity of reactive aggression in children with ADHD and comorbid DBD using functional neuroimaging techniques (fMRI). Eighteen boys with ADHD (age 9-14 years, 10 subjects with comorbid DBD) and 18 healthy controls were administered a modified fMRI-based version of the 'Point Subtraction Aggression Game' to elicit reactive aggressive behaviour. Trials consisted of an 'aggression phase' (punishment for a fictitious opponent) and an 'outcome phase' (presentation of the trial outcome). During the aggression phase, higher aggressive responses of control children were accompanied by higher activation of the ventral anterior cingulate cortex and the temporoparietal junction. Patients displayed inverted results. During the outcome phase, comparison between groups and conditions showed differential activation in the dorsal striatum and bilateral insular when subjects gained points. Losing points was accompanied by differential activation of regions belonging to the insula and the middle temporal sulcus. Data support the hypothesis that deficient inhibitory control mechanisms are related to increased impulsive aggressive behaviour in young people with ADHD and comorbid DBD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Warm-needle moxibustion for spasticity after stroke: A systematic review of randomized controlled trials.

PubMed

Yang, Liu; Tan, Jing-Yu; Ma, Haili; Zhao, Hongjia; Lai, Jinghui; Chen, Jin-Xiu; Suen, Lorna K P

2018-03-22

Spasticity is a common post-stroke complication, and it results in substantial deterioration in the quality of life of patients. Although potential positive effects of warm-needle moxibustion on spasticity after stroke have been observed, evidence on its definitive effect remains uncertain. This study aimed to summarize clinical evidence pertaining to therapeutic effects and safety of warm-needle moxibustion for treating spasticity after stroke. Randomized controlled trials were reviewed systematically on the basis of the Cochrane Handbook for Systematic Reviews of Interventions. The report follows the PRISMA statement. Ten electronic databases (PubMed, CENTRAL, EMBASE, AMED, CINAHL, Web of Science, CBM, CNKI, WanFang, and VIP) were explored, and articles were retrieved manually from two Chinese journals (The Journal of Traditional Chinese Medicine and Zhong Guo Zhen Jiu) through retrospective search. Randomized controlled trials with warm-needle moxibustion as treatment intervention for patients with limb spasm after stroke were included in this review. The risk of bias assessment tool was utilized in accordance with Cochrane Handbook 5.1.0. All included studies reported spasm effect as primary outcome. Effect size was estimated using relative risk, standardized mean difference, or mean difference with a corresponding 95% confidence interval. Review Manager 5.3 was utilized for meta-analysis. Twelve randomized controlled trials with certain methodological flaws and risk of bias were included, and they involved a total of 878 participants. Warm-needle moxibustion was found to be superior to electroacupuncture or acupuncture in reducing spasm and in promoting motor function and daily living activities. Pooled results for spasm effect and motor function were significant when warm-needle moxibustion was compared with electroacupuncture or acupuncture. A comparison of daily living activities indicated significant differences between warm-needle moxibustion and electroacupuncture. However, no difference was observed between warm-needle moxibustion and acupuncture. Warm-needle moxibustion may be a promising intervention to reduce limb spasm as well as improve motor function and daily living activities for stroke patients with spasticity. However, evidence was not conclusive. Rigorously designed randomized controlled trials with sample sizes larger than that in the included trials should be conducted for verification. Copyright © 2018 Elsevier Ltd. All rights reserved.

Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: Trial design and protocol (CONSTRUCT)

PubMed Central

Seagrove, Anne C; Alam, M Fasihul; Alrubaiy, Laith; Cheung, Wai-Yee; Clement, Clare; Cohen, David; Grey, Michelle; Hilton, Mike; Hutchings, Hayley; Morgan, Jayne; Rapport, Frances; Roberts, Stephen E; Russell, Daphne; Russell, Ian; Thomas, Linzi; Thorne, Kymberley; Watkins, Alan; Williams, John G

2014-01-01

Introduction Many patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy. Mortality following emergency colectomy has fallen, but 10% of patients still die within 3 months of surgery. Infliximab and ciclosporin, both immunosuppressive drugs, offer hope for treating steroid-resistant UC as there is evidence of their short-term effectiveness. As there is little long-term evidence, this pragmatic randomised trial, known as Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT), aims to compare the clinical and cost-effectiveness of infliximab and ciclosporin for steroid-resistant UC. Methods and analysis Between May 2010 and February 2013, 52 UK centres recruited 270 patients admitted with acute severe UC who failed to respond to intravenous steroids but did not need surgery. We allocated them at random in equal proportions between infliximab and ciclosporin.The primary clinical outcome measure is quality-adjusted survival, that is survival weighted by Crohn's and Colitis Questionnaire (CCQ) participants’ scores, analysed by Cox regression. Secondary outcome measures include: the CCQ—an extension of the validated but community-focused UK Inflammatory Bowel Disease Questionnaire (IBDQ) to include patients with acute severe colitis and stoma; two general quality of life measures—EQ-5D and SF-12; mortality; survival weighted by EQ-5D; emergency and planned colectomies; readmissions; incidence of adverse events including malignancies, serious infections and renal disorders; disease activity; National Health Service (NHS) costs and patient-borne costs. Interviews investigate participants’ views on therapies for acute severe UC and healthcare professionals’ views on the two drugs and their administration. Ethics and dissemination The Research Ethics Committee for Wales has given ethical approval (Ref. 08/MRE09/42); each participating Trust or Health Board has given NHS Reseach & Development approval. We plan to present trial findings at international and national conferences and publish in high-impact peer-reviewed journals. Trial registration number ISRCTN: 22663589; EudraCT number: 2008-001968-36 PMID:24785401

Does self-efficacy mediate functional change in older adults participating in an exercise program after hip fracture? A randomized controlled trial.

PubMed

Chang, Feng-Hang; Latham, Nancy K; Ni, Pengsheng; Jette, Alan M

2015-06-01

To examine whether self-efficacy mediated the effect of the Home-based Post-Hip Fracture Rehabilitation program on activity limitations in older adults after hip fracture and whether the mediating effect was different between sex and age groups. Randomized controlled trial. Community. Participants with hip fracture (N=232; mean age ± SD, 79±9.4y) were randomly assigned to intervention (n=120, 51.7%) and attention control (n=112, 48.3%) groups. The 6-month intervention, the Home-based Post-Hip Fracture Rehabilitation, is a functionally oriented, home-based exercise program. Data were collected at baseline, postintervention (6mo), and follow-up (9mo). Activity Measure for Post-Acute Care. The mediating effect of the Home-based Post-Hip Fracture Rehabilitation program on Basic Mobility function through self-efficacy for exercise was significant at 9 months (βindirect=.21). Similarly, the mediating effect of the intervention on Daily Activity function through self-efficacy for exercise was significant at 9 months (βindirect=.49). In subgroup analyses, the mediating effect was significant at 9 months in the younger group (age, ≤79y) in comparison to the older group and was significant in women in comparison to men. Self-efficacy may play a partial mediating role in the effect on some longer-term functional outcomes in the Home-based Post-Hip Fracture Rehabilitation intervention. The results suggest that program components that target self-efficacy should be incorporated in future hip fracture rehabilitation interventions. Age and sex of the targeted participants may also need to be considered when developing interventions. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Does self-efficacy mediate functional change in older adults participating in an exercise program after hip fracture? A randomized control trial

PubMed Central

Latham, Nancy K.; Ni, Pengsheng; Jette, Alan M.

2015-01-01

Objectives This study examined whether self-efficacy mediated the effect of the HIP Rehab exercise program on activity limitations in older adults after hip fracture, and whether the mediation effect was different between different gender and age groups. Design Randomized controlled trial (RCT) Setting Community Participants Two hundred and thirty two participants aged 79±9.4 years with hip fracture were randomly assigned to intervention (n=120) or attention control (n=112) groups. Interventions The 6-month intervention, the HIP Rehab, is a functionally-oriented, home-based exercise program. Data was collected at baseline, post-intervention (6 months), and follow-up (9 months). Main outcome measure Activity Measure for Post-Acute Care (AM-PAC) Results The mediation effect of the HIP Rehab exercise program on Basic Mobility function through self-efficacy for exercise was significant at 9 months (βindirect=0.21). Similarly, the mediation effect of the intervention on Daily Activity function through self-efficacy for exercise was significant at 9 months (βindirect=0.49). In subgroup analyses, the mediation effect was significant at 9 months in the younger group (≤79 years old) in comparison to the older group, and was significant in females in comparison to males. Conclusion Self-efficacy may play a partial mediating role for the effect on some longer-term functional outcomes in the HIP Rehab intervention. The results suggest that program components that target self-efficacy should be incorporated in the future hip fracture rehabilitation interventions. Age and gender of the targeted participants may also need to be considered when developing interventions. PMID:25701101

Radiofrequency in female external genital cosmetics and sexual function: a randomized clinical trial.

PubMed

Lordêlo, Patrícia; Leal, Mariana Robatto Dantas; Brasil, Cristina Aires; Santos, Juliana Menezes; Lima, Maria Clara Neves Pavie Cardoso; Sartori, Marair Gracio Ferreira

2016-11-01

Female sexual behavior goes through cultural changes constantly, and recently, some women have shown the desire the ideal genitalia. In this study, we aimed to evaluate clinical responses to nonablative radiofrequency (RF) in terms of its cosmetic outcome in the female external genitalia and its effect on sexual function. A single-masking randomized controlled trial was conducted in 43 women (29 sexually active) who were unsatisfied with the appearance of their external genitalia. The women were divided into an RF group (n = 21, 14 sexually active) and a control group (n = 22, 15 sexually active). Eight sessions of RF were performed once a week. Photographs (taken before the first session and 8 days after the last session) were evaluated by the women and three blinded health professionals by using two 3-point Likert scales (unsatisfied, unchanged, and satisfied; and worst, unchanged, and improved). Sexual function was evaluated using the Female Sexual Function Index (FSFI) and analyzed using the Student t test. Women's satisfaction and health professional evaluation were analyzed using the chi-square test and inter- and intragroup binomial comparisons. Satisfaction response rates were 76 and 27 % for the RF and control groups, respectively (p = 0.001). All professionals found a clinical improvement association in the treated group with RF in comparison with the control group (p < 0.01). The overall FSFI sexual function score increased by 3.51 points in the RF group vs 0.1 points in the control group (p = 0.003). RF is an alternative for attaining a cosmetic outcome for the female external genitalia, with positives changes in patients' satisfaction and FSFI scores.

Clown intervention to reduce preoperative anxiety in children and parents: a randomized controlled trial.

PubMed

Dionigi, Alberto; Sangiorgi, Diego; Flangini, Roberto

2014-03-01

This study investigated whether a clown doctor intervention could reduce preoperative anxiety in children hospitalized for minor surgery and in their parents. A randomized controlled trial was conducted with 77 children and 119 parents: the clown group consisted of 52 children accompanied in the preoperating room by their parents (n = 89) and two clowns while the comparison group consisted of children accompanied by the parents only. The clown intervention significantly reduced the children's preoperative anxiety: children benefited from the clown's presence and showed better adjustment than children in the comparison group. Mothers in Comparison Group showed higher anxiety.

Prediction of activity type in preschool children using machine learning techniques.

PubMed

Hagenbuchner, Markus; Cliff, Dylan P; Trost, Stewart G; Van Tuc, Nguyen; Peoples, Gregory E

2015-07-01

Recent research has shown that machine learning techniques can accurately predict activity classes from accelerometer data in adolescents and adults. The purpose of this study is to develop and test machine learning models for predicting activity type in preschool-aged children. Participants completed 12 standardised activity trials (TV, reading, tablet game, quiet play, art, treasure hunt, cleaning up, active game, obstacle course, bicycle riding) over two laboratory visits. Eleven children aged 3-6 years (mean age=4.8±0.87; 55% girls) completed the activity trials while wearing an ActiGraph GT3X+ accelerometer on the right hip. Activities were categorised into five activity classes: sedentary activities, light activities, moderate to vigorous activities, walking, and running. A standard feed-forward Artificial Neural Network and a Deep Learning Ensemble Network were trained on features in the accelerometer data used in previous investigations (10th, 25th, 50th, 75th and 90th percentiles and the lag-one autocorrelation). Overall recognition accuracy for the standard feed forward Artificial Neural Network was 69.7%. Recognition accuracy for sedentary activities, light activities and games, moderate-to-vigorous activities, walking, and running was 82%, 79%, 64%, 36% and 46%, respectively. In comparison, overall recognition accuracy for the Deep Learning Ensemble Network was 82.6%. For sedentary activities, light activities and games, moderate-to-vigorous activities, walking, and running recognition accuracy was 84%, 91%, 79%, 73% and 73%, respectively. Ensemble machine learning approaches such as Deep Learning Ensemble Network can accurately predict activity type from accelerometer data in preschool children. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Methods to decrease blood loss and transfusion requirements for liver transplantation.

PubMed

Gurusamy, Kurinchi Selvan; Pissanou, Theodora; Pikhart, Hynek; Vaughan, Jessica; Burroughs, Andrew K; Davidson, Brian R

2011-12-07

Excessive blood loss and increased blood transfusion requirements may have significant impact on the short-term and long-term outcomes after liver transplantation. To compare the potential benefits and harms of different methods of decreasing blood loss and blood transfusion requirements during liver transplantation. We searched The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and metaRegister of Controlled Trials until September 2011. We included all randomised clinical trials that were performed to compare various methods of decreasing blood loss and blood transfusion requirements during liver transplantation. Two authors independently identified the trials and extracted the data. We analysed the data with both the fixed-effect and the random-effects model using RevMan Analysis. For each outcome we calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI) based on available data analysis. We also conducted network meta-analysis. We included 33 trials involving 1913 patients. The sample size in the trials varied from 8 to 209 participants. The interventions included pharmacological interventions (aprotinin, tranexamic acid, epsilon amino caproic acid, antithrombin 3, recombinant factor (rFvIIa), oestrogen, prostaglandin, epinephrine), blood substitutes (blood components rather than whole blood, hydroxy-ethyl starch, thromboelastography), and cardiovascular interventions (low central venous pressure). All the trials were of high risk of bias. Primary outcomes were reported in at least two trials for the following comparisons: aprotinin versus control, tranexamic acid versus control, recombinant factor VIIa (rFVIIa) versus control, and tranexamic acid versus aprotinin. There were no significant differences in the 60-day mortality (3 trials; 6/161 (3.7%) in the aprotinin group versus 8/119 (6.7%) in the control group; RR 0.52; 95% CI 0.18 to 1.45), primary graft non-function (2 trials; 0/128 (0.0%) in the aprotinin group versus 4/89 (4.5%) in the control group; RR 0.15; 95% CI 0.02 to 1.25), retransplantation (3 trials; 2/256 (0.8%) in the aprotinin group versus 12/178 (6.7%) in the control group; RR 0.21; 95% CI 0.02 to 1.79), or thromboembolic episodes (3 trials; 4/161 (2.5%) in the aprotinin group versus 5/119 (4.2%) in the control group; RR 0.59; 95% CI 0.19 to 1.84) between the aprotinin and control groups. There were no significant differences in the 60-day mortality (3 trials; 4/83 (4.8%) in the tranexamic acid group versus 5/56 (8.9%) in the control group; RR 0.55; 95% CI 0.17 to 1.76), retransplantation (2 trials; 3/41 (7.3%) in the tranexamic acid group versus 3/36 (8.3%) in the control group; RR 0.79; 95% CI 0.18 to 3.48), or thromboembolic episodes (5 trials; 5/103 (4.9%) in the tranexamic acid group versus 1/76 (1.3%) in the control group; RR 2.20; 95% CI 0.38 to 12.64) between the tranexamic acid and control groups. There were no significant differences in the 60-day mortality (3 trials; 8/195 (4.1%) in the recombinant factor VIIa (rFVIIa) group versus 2/91 (2.2%) in the control group; RR 1.51; 95% CI 0.33 to 6.95), thromboembolic episodes (2 trials; 24/185 (13.0%) in the rFVIIa group versus 8/81 (9.9%) in the control group; RR 1.38; 95% CI 0.65 to 2.91), or serious adverse events (2 trials; 90/185 (48.6%) in the rFVIIa group versus 30/81 (37.0%) in the control group; RR 1.30; 95% CI 0.94 to 1.78) between the rFVIIa and control groups. There were no significant differences in the 60-day mortality (2 trials; 6/91 (6.6%) in the tranexamic acid group versus 1/87 (1.1%) in the aprotinin group; RR 4.12; 95% CI 0.71 to 23.76) or thromboembolic episodes (2 trials; 4/91 (4.4%) in the tranexamic acid group versus 2/87 (2.3%) in the aprotinin group; RR 1.97; 95% CI 0.37 to 10.37) between the tranexamic acid and aprotinin groups. The remaining outcomes in the above comparisons and the remaining comparisons included only only trial under the primary outcome or the outcome was not reported at all in the trials. There were no significant differences in the mortality, primary graft non-function, graft failure, retransplantation, thromboembolic episodes, or serious adverse events in any of these comparisons. However, the confidence intervals were wide, and it is not possible to reach any conclusion on the safety of the interventions. None of the trials reported the quality of life in patients.Secondary outcomes were reported in at least two trials for the following comparisons - aprotinin versus control, tranexamic acid versus control, rFVIIa versus control, thromboelastography versus control, and tranexamic acid versus aprotinin. There was significantly lower allogeneic blood transfusion requirements in the aprotinin group than the control group (8 trials; 185 patients in aprotinin group and 190 patients in control group; SMD -0.61; 95% CI -0.82 to -0.40). There were no significant differences in the allogeneic blood transfusion requirements between the tranexamic acid and control groups (4 trials; 93 patients in tranexamic acid group and 66 patients in control group; SMD -0.27; 95% CI -0.59 to 0.06); rFVIIa and control groups (2 trials; 141 patients in rFVIIa group and 80 patients in control group; SMD -0.05; 95% CI -0.32 to 0.23); thromboelastography and control groups (2 trials; 31 patients in thromboelastography group and 31 patients in control group; SMD -0.73; 95% CI -1.69 to 0.24); or between the tranexamic acid and aprotinin groups (3 trials; 101 patients in tranexamic acid group and 97 patients in aprotinin group; SMD -0.09; 95% CI -0.36 to 0.19). The remaining outcomes in the above comparisons and the remaining comparisons included only only trial under the primary outcome or the outcome was not reported at all in the trials. There were no significant differences in the blood loss, transfusion requirements, hospital stay, or intensive care unit stay in most of the comparisons. Aprotinin, recombinant factor VIIa, and thromboelastography groups may potentially reduce blood loss and transfusion requirements. However, risks of systematic errors (bias) and risks of random errors (play of chance) hamper the confidence in this conclusion. We need further well-designed randomised trials with low risk of systematic error and low risk of random errors before these interventions can be supported or refuted.

Evidence of MAOA genotype involvement in spatial ability in males

PubMed Central

Mueller, Sven C.; Cornwell, Brian R.; Grillon, Christian; MacIntyre, Jessica; Gorodetsky, Elena; Goldman, David; Pine, Daniel S.; Ernst, Monique

2014-01-01

Although the Monoamine Oxidase-A (MAOA) gene has been linked to spatial learning and memory in animal models, convincing evidence in humans is lacking. Performance on an ecologically-valid, virtual computer-based equivalent of the Morris Water Maze task was compared between 28 healthy males with the low MAOA transcriptional activity and 41 healthy age- and IQ-matched males with the high MAOA transcriptional activity. The results revealed consistently better performance (reduced heading error, shorter path length, and reduced failed trials) for the high MAOA activity individuals relative to the low activity individuals. By comparison, groups did not differ on pre-task variables or strategic measures such as first-move latency. The results provide novel evidence of MAOA gene involvement in human spatial navigation using a virtual analogue of the Morris Water Maze task. PMID:24671068

Eye movements reflect and shape strategies in fraction comparison

PubMed Central

Ischebeck, Anja; Weilharter, Marina; Körner, Christof

2016-01-01

The comparison of fractions is a difficult task that can often be facilitated by separately comparing components (numerators and denominators) of the fractions—that is, by applying so-called component-based strategies. The usefulness of such strategies depends on the type of fraction pair to be compared. We investigated the temporal organization and the flexibility of strategy deployment in fraction comparison by evaluating sequences of eye movements in 20 young adults. We found that component-based strategies could account for the response times and the overall number of fixations observed for the different fraction pairs. The analysis of eye movement sequences showed that the initial eye movements in a trial were characterized by stereotypical scanning patterns indicative of an exploratory phase that served to establish the kind of fraction pair presented. Eye movements that followed this phase adapted to the particular type of fraction pair and indicated the deployment of specific comparison strategies. These results demonstrate that participants employ eye movements systematically to support strategy use in fraction comparison. Participants showed a remarkable flexibility to adapt to the most efficient strategy on a trial-by-trial basis. Our results confirm the value of eye movement measurements in the exploration of strategic adaptation in complex tasks. PMID:26039819

Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF).

PubMed

McMurray, John J V; Packer, Milton; Desai, Akshay S; Gong, Jim; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael R

2013-09-01

Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides. Patients with chronic HF, NYHA class II-IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death. PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF. NCT01035255.

Unfractionated or low-molecular weight heparin for induction of remission in ulcerative colitis.

PubMed

Chande, N; McDonald, J W; Macdonald, J K

2008-04-16

There are a limited number of treatment options for patients with ulcerative colitis (UC). An increased risk of thrombosis in UC coupled with an observation that UC patients being treated with anticoagulant therapy for thrombotic events had an improvement in their bowel symptoms led to trials examining the use of unfractionated heparin (UFH) and low molecular weight heparins (LMWH) in patients with active UC. To review randomized trials examining the efficacy of unfractionated heparin (UFH) or low molecular weight heparins (LMWH) for remission induction in patients with ulcerative colitis. The MEDLINE (PUBMED), and EMBASE databases, The Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD group specialized trials register, review papers on ulcerative colitis, and references from identified papers were searched in an effort to identify all randomized trials studying UFH or LMWH use in patients with ulcerative colitis. Abstracts from major gastroenterological meetings were searched to identify research published in abstract form only. Each author independently reviewed potentially relevant trials to determine their eligibility for inclusion based on the criteria identified above. The Jadad scale was used to assess study quality. Studies published in abstract form only were included if the authors could be contacted for further information. A data extraction form was developed and used to extract data from included studies. At least 2 authors independently extracted data. Any disagreements were resolved by consensus. Data were analyzed using Review Manager (RevMan 4.2.9). Data were analyzed on an intention-to-treat basis, and treated dichotomously. In cross-over studies, only data from the first arm were included. The primary endpoint was induction of remission, as defined by the studies. Data were combined for analysis if they assessed the same treatments (UFH or LMWH versus placebo or other therapy). If a comparison was only assessed in a single trial, P-values were derived using the chi-square test. If the comparison was assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals (95% CI). The presence of heterogeneity among studies was assessed using the chi-square test (a P value of 0.10 was regarded as statistically significant). If statistically significant heterogeneity was identified the odds ratio and 95% CI were calculated using a random effects model. There were 2 randomized, double-blind studies assessing LMWH versus placebo for the treatment of mild-moderate active UC. Various outcomes were assessed in the 2 studies. LMWH showed no benefit over placebo in any outcome, including clinical remission (OR 1.09; 95% CI 0.26 to 4.63; P = 0.91), clinical improvement (OR 0.73; 95% CI 0.32 to 1.66; P = 0.45 and OR 1.09; 95% CI 0.18 to 6.58; P = 0.92 in the two studies, respectively), endoscopic improvement (OR 1.35; 95% CI 0.29 to 6.18; P = 0.70), or histological improvement (OR 2.00; 95% CI 0.45 to 8.96; P = 0.37). LMWH was also not beneficial when added to standard therapy in a randomized open-label trial in which the outcome measures included clinical remission (OR 0.71; 95% CI 0.17 to 2.95; P = 0.64), clinical improvement (OR 2.00; 95% CI 0.31 to 12.75; P = 0.46), endoscopic remission (OR 0.71; 95% CI 0.17 to 2.95; P = 0.64), or endoscopic improvement (OR 1.40; 95% CI 0.34 to 5.79; P = 0.64). LMWH was well-tolerated and provided no significant benefit for quality of life. One study examining UFH versus corticosteroids in the treatment of severe UC demonstrated inferiority of UFH in clinical improvement as an outcome measure (OR 0.02; 95% CI 0 to 0.40; P = 0.01). Patients assigned to UFH did not improve clinically. More patients assigned to UFH had rectal hemorrhage as an adverse event. There is no evidence to support the use of UFH or LMWH for the treatment of active UC. No further trials examining these drugs for patients with UC are warranted, except perhaps a trial of UFH in patients with mild disease. Any benefit found would need to be weighed against a possible increased risk of rectal bleeding in patients with active UC.

An mHealth App for Supporting Quitters to Manage Cigarette Cravings With Short Bouts of Physical Activity: A Randomized Pilot Feasibility and Acceptability Study.

PubMed

Hassandra, Mary; Lintunen, Taru; Hagger, Martin S; Heikkinen, Risto; Vanhala, Mauno; Kettunen, Tarja

2017-05-26

While gains in reducing smoking rates in Finland have been made, prevalence rates are still substantial. Relapse rates among smokers engaged in quit-smoking programs are high. Physical activity has been proposed as one means to help smokers manage cravings. Software and apps on mobile phone and handheld devices offer an opportunity to communicate messages on how to use physical activity to manage cravings as part of quit-smoking programs. We aimed to test the feasibility, acceptability, usability, and preliminary efficacy of an mHealth mobile phone app, Physical activity over Smoking (PhoS), to assist smokers in quitting smoking in a randomized controlled trial. The app was designed to prompt smokers to engage in physical activities to manage their smoking cravings. Regular smokers (n=44) attended a group-based behavioral counselling program aimed at promoting physical activity as an additional aid to quit. After quit day, participants were randomly allocated to an intervention (n=25) or to a comparison (n=19) group. Participants in the intervention group were provided with the PhoS app and training on how to use it to assist with relapse prevention. Participants in the comparison condition were provided with generalized relapse prevention training. Some participants reported that the PhoS app was useful in assisting them to successfully manage their cigarette cravings, although compliance across the sample was modest and participants reported low levels of usability. Participants receiving the PhoS app did not report greater abstinence than those who did not receive the app. However, participants receiving the app were more likely to report greater abstinence if they did not use pharmacological support, while those who did not receive the app reported greater abstinence when using pharmacological support. Participants receiving the app reported greater levels of physical activity than those who did not. Results revealed that the app resulted in better retention. The PhoS app showed some potential to reduce abstinence among participants not using pharmacological therapy and to increase physical activity. However, problems with usability and lack of effects on abstinence raise questions over the app's long-term effectiveness. Future research should prioritize further development of the app to maximize usability and test effects of the intervention independent of quit-smoking programs. International Standard Randomized Controlled Trial Number (ISRCTN): 55259451; http://www.controlled-trials.com/ISRCTN55259451 (Archived by WebCite at http://www.webcitation.org/6cKF2mzEI). ©Mary Hassandra, Taru Lintunen, Martin S Hagger, Risto Heikkinen, Mauno Vanhala, Tarja Kettunen. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 26.05.2017.

Recommendations for imaging tumor response in neurofibromatosis clinical trials

PubMed Central

Ardern-Holmes, Simone L.; Babovic-Vuksanovic, Dusica; Barker, Fred G.; Connor, Steve; Evans, D. Gareth; Fisher, Michael J.; Goutagny, Stephane; Harris, Gordon J.; Jaramillo, Diego; Karajannis, Matthias A.; Korf, Bruce R.; Mautner, Victor; Plotkin, Scott R.; Poussaint, Tina Y.; Robertson, Kent; Shih, Chie-Schin; Widemann, Brigitte C.

2013-01-01

Objective: Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. Methods: Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. Results: MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. Conclusions: The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors. PMID:24249804

Recommendations for imaging tumor response in neurofibromatosis clinical trials.

PubMed

Dombi, Eva; Ardern-Holmes, Simone L; Babovic-Vuksanovic, Dusica; Barker, Fred G; Connor, Steve; Evans, D Gareth; Fisher, Michael J; Goutagny, Stephane; Harris, Gordon J; Jaramillo, Diego; Karajannis, Matthias A; Korf, Bruce R; Mautner, Victor; Plotkin, Scott R; Poussaint, Tina Y; Robertson, Kent; Shih, Chie-Schin; Widemann, Brigitte C

2013-11-19

Neurofibromatosis (NF)-related benign tumors such as plexiform neurofibromas (PN) and vestibular schwannomas (VS) can cause substantial morbidity. Clinical trials directed at these tumors have become available. Due to differences in disease manifestations and the natural history of NF-related tumors, response criteria used for solid cancers (1-dimensional/RECIST [Response Evaluation Criteria in Solid Tumors] and bidimensional/World Health Organization) have limited applicability. No standardized response criteria for benign NF tumors exist. The goal of the Tumor Measurement Working Group of the REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) committee is to propose consensus guidelines for the evaluation of imaging response in clinical trials for NF tumors. Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members. MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors.

Active versus passive adverse event reporting after pediatric chiropractic manual therapy: study protocol for a cluster randomized controlled trial.

PubMed

Pohlman, Katherine A; Carroll, Linda; Tsuyuki, Ross T; Hartling, Lisa; Vohra, Sunita

2017-12-01

Patient safety performance can be assessed with several systems, including passive and active surveillance. Passive surveillance systems provide opportunity for health care personnel to confidentially and voluntarily report incidents, including adverse events, occurring in their work environment. Active surveillance systems systematically monitor patient encounters to seek detailed information about adverse events that occur in work environments; unlike passive surveillance, active surveillance allows for collection of both numerator (number of adverse events) and denominator (number of patients seen) data. Chiropractic manual therapy is commonly used in both adults and children, yet few studies have been done to evaluate the safety of chiropractic manual therapy for children. In an attempt to evaluate this, this study will compare adverse event reporting in passive versus active surveillance systems after chiropractic manual therapy in the pediatric population. This cluster randomized controlled trial aims to enroll 70 physicians of chiropractic (unit of randomization) to either passive or active surveillance system to report adverse events that occur after treatment for 60 consecutive pediatric (13 years of age and younger) patient visits (unit of analysis). A modified enrollment process with a two-phase consent procedure will be implemented to maintain provider blinding and minimize dropouts. The first phase of consent is for the provider to confirm their interest in a trial investigating the safety of chiropractic manual therapy. The second phase ensures that they understand the specific requirements for the group to which they were randomized. Percentages, incidence estimates, and 95% confidence intervals will be used to describe the count of reported adverse events in each group. The primary outcome will be the number and quality of the adverse event reports in the active versus the passive surveillance group. With 80% power and 5% one-sided significance level, the sample size was calculated to be 35 providers in each group, which includes an 11% lost to follow-up of chiropractors and 20% of patient visits. This study will be the first direct comparison of adverse event reporting using passive versus active surveillance. It is also the largest prospective evaluation of adverse events reported after chiropractic manual therapy in children, identified as a major gap in the academic literature. ClinicalTrials.gov, ID: NCT02268331 . Registered on 10 October 2014.

Conflict monitoring and adaptation in individuals at familial risk for developing bipolar disorder.

PubMed

Patino, Luis R; Adler, Caleb M; Mills, Neil P; Strakowski, Stephen M; Fleck, David E; Welge, Jeffrey A; DelBello, Melissa P

2013-05-01

To examine conflict monitoring and conflict-driven adaptation in individuals at familial risk for developing bipolar disorder. We recruited 24 adolescents who had a parent with bipolar disorder and 23 adolescents with healthy parents. Participants completed an arrow version of the Eriksen Flanker Task that included trials with three levels of conflict: neutral, congruent, and incongruent flanks. Differences in performance were explored based upon the level of conflict in the current and previous trials. Individuals at risk for developing bipolar disorder performed more slowly than youth with healthy parents in all trials. Analyses evaluating sequential effects revealed that at-risk subjects responded more slowly than youth of healthy parents for all trial types when preceded by an incongruent trial, for incongruent trials preceded by congruent trials, and for neutral and congruent trials when preceded by neutral trials. In contrast to the comparison group, at-risk adolescents failed to display a response time advantage for incongruent trials preceded by an incongruent trial. When removing subjects with attention-deficit hyperactivity disorder (ADHD), differences between groups in response time fell below significant level, but a difference in sequence modulation remained significant. Subjects at risk for bipolar disorder also displayed greater intra-subject response time variability for incongruent and congruent trials compared with the comparison adolescents. No differences in response accuracy were observed between groups. Adolescents at risk for developing bipolar disorder displayed specific deficits in cognitive flexibility, which might be useful as a potential marker related to the development of bipolar disorder. © 2013 John Wiley and Sons A/S. Published by Blackwell Publishing Ltd.

Perioperative Dextromethorphan as an Adjunct for Postoperative Pain: a Meta-Analysis of Randomized Controlled Trials

PubMed Central

King, Michael R.; Ladha, Karim S.; Gelineau, Amanda M.; Anderson, T. Anthony

2015-01-01

Background N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to reduce perioperative pain and opioid use. We performed a meta-analysis to determine whether the use of perioperative dextromethorphan lowers opioid consumption or pain scores. Methods PubMed, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, pubget, and Embase were searched. Studies were included if they were randomized, double-blinded, placebo controlled trials written in English, performed on patients ≥12 years. For comparison of opioid use, included studies tracked total consumption of intravenous or intramuscular opioids over 24 to 48 hours. Pain score comparisons were performed at 1 hour, 4 to 6 hours, and 24 hours postoperatively. Difference in means (MD) was used for effect size. Results Forty studies were identified and 21 were eligible for one or more comparisons. In 848 patients from 14 trials, opioid consumption favored dextromethorphan (MD -10.51 mg intravenous morphine equivalents; 95% confidence interval [CI]: -16.48 mg to -4.53 mg; p = 0.0006). In 884 patients from 13 trials, pain at 1 hour favored dextromethorphan (MD -1.60; 95% CI: -1.89 to -1.31; p < 0.00001). In 950 patients from 13 trials, pain at 4-6 hours favored dextromethorphan (MD -0.89; 95% CI: -1.11 to -0.66; p < 0.00001). In 797 patients from 12 trials, pain at 24 hours favored dextromethorphan (MD -0.92; 95% CI: -1.24 to -0.60; p < 0.00001). Conclusions This meta-analysis suggests dextromethorphan use perioperatively reduces postoperative opioid consumption at 24-48 hours and pain scores at 1, 4-6, and 24 hours. PMID:26587683

Perioperative Dextromethorphan as an Adjunct for Postoperative Pain: A Meta-analysis of Randomized Controlled Trials.

PubMed

King, Michael R; Ladha, Karim S; Gelineau, Amanda M; Anderson, T Anthony

2016-03-01

N-methyl-D-aspartate receptor antagonists have been shown to reduce perioperative pain and opioid use. The authors performed a meta-analysis to determine whether the use of perioperative dextromethorphan lowers opioid consumption or pain scores. PubMed, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Pubget, and EMBASE were searched. Studies were included if they were randomized, double-blinded, placebo-controlled trials written in English, and performed on patients 12 yr or older. For comparison of opioid use, included studies tracked total consumption of IV or intramuscular opioids over 24 to 48 h. Pain score comparisons were performed at 1, 4 to 6, and 24 h postoperatively. Difference in means (MD) was used for effect size. Forty studies were identified and 21 were eligible for one or more comparisons. In 848 patients from 14 trials, opioid consumption favored dextromethorphan (MD, -10.51 mg IV morphine equivalents; 95% CI, -16.48 to -4.53 mg; P = 0.0006). In 884 patients from 13 trials, pain at 1 h favored dextromethorphan (MD, -1.60; 95% CI, -1.89 to -1.31; P < 0.00001). In 950 patients from 13 trials, pain at 4 to 6 h favored dextromethorphan (MD, -0.89; 95% CI, -1.11 to -0.66; P < 0.00001). In 797 patients from 12 trials, pain at 24 h favored dextromethorphan (MD, -0.92; 95% CI, -1.24 to -0.60; P < 0.00001). This meta-analysis suggests that dextromethorphan use perioperatively reduces the postoperative opioid consumption at 24 to 48 h and pain scores at 1, 4 to 6, and 24 h.

Gefitinib in advanced non-small cell lung cancer: does it deserve a second chance?

PubMed

Stinchcombe, Thomas E; Socinski, Mark A

2008-09-01

There has been intense investigation into the epidermal growth factor receptor (EGFR) as a therapeutic target in the treatment of non-small cell lung cancer (NSCLC). Currently there are two EGFR tyrosine kinase inhibitors, erlotinib and gefitinib, approved for the treatment of advanced NSCLC. In a phase III trial (BR.21), treatment with erlotinib resulted in a statistically significant improvement in overall survival in patients who had experienced progression after one or two previous chemotherapy treatments in comparison with best supportive care (BSC). In contrast, in the Iressa Survival Evaluation in Lung Cancer (ISEL) trial, treatment with gefitinib did not result in a statistically significant improvement in overall survival time in comparison with BSC in patients who had received one or two previous chemotherapy treatments and were refractory to or intolerant of the previous chemotherapy. After the results of the ISEL trial, the U.S. Food and Drug Administration restricted the use of gefitinib, and gefitinib was effectively removed from routine clinical practice within the U.S. However, gefitinib was approved in other countries and clinical trials investigating gefitinib continued. Recently the Iressa Non-small cell lung cancer Trial Evaluating REsponse and Survival against Taxotere (INTEREST) trial met the primary endpoint of demonstrating noninferiority in terms of overall survival for gefitinib (250 mg daily) in comparison with docetaxel (75 mg/m(2) every 3 weeks). Patients treated with gefitinib experienced a lower rate of treatment-related toxicity and higher rate of improvement in quality of life. Results of recent gefitinib trials have been provocative, and suggest a role for gefitinib in the treatment of advanced NSCLC.

Active Video Games in Schools and Effects on Physical Activity and Health: A Systematic Review.

PubMed

Norris, Emma; Hamer, Mark; Stamatakis, Emmanuel

2016-05-01

To assess the quality of evidence for the effects of school active video game (AVG) use on physical activity and health outcomes. Online databases (ERIC, PsycINFO, PubMed, SPORTDiscus, and Web of Science) and gray literature were searched. Inclusion criteria were the use of AVGs in school settings as an intervention; assessment of at least 1 health or physical activity outcome; and comparison of outcomes with either a control group or comparison phase. Studies featuring AVGs within complex interventions were excluded. Study quality was assessed using the Effective Public Health Practice Project tool. Twenty-two reports were identified: 11 assessed physical activity outcomes only, 5 assessed motor skill outcomes only, and 6 assessed both physical activity and health outcomes. Nine out of 14 studies found greater physical activity in AVG sessions compared with controls; mostly assessed by objective measures in school time only. Motor skills were found to improve with AVGs vs controls in all studies but not compared with other motor skill interventions. Effects of AVGs on body composition were mixed. Study quality was low in 16 studies and moderate in the remaining 6, with insufficient detail given on blinding, participation rates, and confounding variables. There is currently insufficient evidence to recommend AVGs as efficacious health interventions within schools. Higher quality AVG research utilizing randomized controlled trial designs, larger sample sizes, and validated activity measurements beyond the school day is needed. Copyright © 2016 Elsevier Inc. All rights reserved.

Profiling clinical cancer research across the Atlantic: a review of research and its characteristics presented at ASCO and ESMO Congresses during the last decade.

PubMed

Pentheroudakis, George; Krikelis, Dimitrios; Cervantes, Andres; Vermorken, Jan; Pavlidis, Nicholas

2012-10-01

The comparison of clinical cancer research characteristics across the Atlantic and their evolution over time have not been studied to date. We collected oral presentations on breast, lung and colorectal cancer at ASCO (n=506) and ESMO (n=239) Congresses in years 2000-2010. EU-originated research constituted 52% of all ASCO presentations while US-research 26.7% of ESMO Congress presentations. Industry sponsorship was reported in 24.8% of ASCO vs. 31.8% of ESMO Congress trials. ASCO-presented trials were larger with longer follow-up periods but were blinded less often. ESMO-presented trials used Event-Free Survival (EFS, 38.1%) and Surrogate (18.4%) primary endpoints and reported positive primary endpoints (65%) more often than ASCO-presented trials. Interim analysis resulted in discontinuation of a trial more often at ASCO Congress (8.3% vs. 3.2%). ASCO Congress-presented research was more often published (69.2% vs. 59.8% at ESMO) at higher impact factor journals. Strong trends over the decade were seen for more frequent industry sponsorship, blinded design, larger sample size, early interim discontinuation, use of EFS endpoints and biomarker evaluation. Cancer clinical research is a complex scientific activity with common global but also distinct characteristics at the two sides of the Atlantic. Copyright © 2011 Elsevier Ltd. All rights reserved.

Study protocol: can a school gardening intervention improve children’s diets?

PubMed Central

2012-01-01

Background The current academic literature suggests there is a potential for using gardening as a tool to improve children’s fruit and vegetable intake. This study is two parallel randomised controlled trials (RCT) devised to evaluate the school gardening programme of the Royal Horticultural Society (RHS) Campaign for School Gardening, to determine if it has an effect on children’s fruit and vegetable intake. Method/Design Trial One will consist of 26 schools; these schools will be randomised into two groups, one to receive the intensive intervention as “Partner Schools” and the other to receive the less intensive intervention as “Associate Schools”. Trial Two will consist of 32 schools; these schools will be randomised into either the less intensive intervention “Associate Schools” or a comparison group with delayed intervention. Baseline data collection will be collected using a 24-hour food diary (CADET) to collect data on dietary intake and a questionnaire exploring children’s knowledge and attitudes towards fruit and vegetables. A process measures questionnaire will be used to assess each school’s gardening activities. Discussion The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children’s fruit and vegetable intake. The evaluation will provide valuable information for designing future research in primary school children’s diets and school based interventions. Trial registration ISRCTN11396528 PMID:22537179

A randomized, controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil as a treatment of agitated behaviour in dementia

PubMed Central

2013-01-01

Background Lavender essential oil shows evidence of sedative properties in neurophysiological and animal studies but clinical trials of its effectiveness as a treatment of agitation in people with dementia have shown mixed results. Study methods have varied widely, however, making comparisons hazardous. To help remedy previous methodological shortcomings, we delivered high grade lavender oil in specified amounts to nursing home residents whose agitated behaviours were recorded objectively. Methods 64 nursing home residents with frequent physically agitated behaviours were entered into a randomized, single-blind cross-over trial of dermally-applied, neurophysiologically active, high purity 30% lavender oil versus an inactive control oil. A blinded observer counted the presence or absence of target behaviours and rated participants’ predominant affect during each minute for 30 minutes prior to exposure and for 60 minutes afterwards. Results Lavender oil did not prove superior to the control oil in reducing the frequency of physically agitated behaviours or in improving participants’ affect. Conclusions Studies of essential oils are constrained by their variable formulations and uncertain pharmacokinetics and so optimal dosing and delivery regimens remain speculative. Notwithstanding this, topically delivered, high strength, pure lavender oil had no discernible effect on affect and behaviour in a well-defined clinical sample. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN 12609000569202) PMID:24219098

The effectiveness of ICT-based neurocognitive and psychosocial rehabilitation programmes in people with mild dementia and mild cognitive impairment using GRADIOR and ehcoBUTLER: study protocol for a randomised controlled trial.

PubMed

Vanova, Martina; Irazoki, Eider; García-Casal, J Antonio; Martínez-Abad, Fernando; Botella, Cristina; Shiells, Kate R; Franco-Martín, Manuel A

2018-02-12

Cognitive rehabilitation is a highly individualised, non-pharmacological intervention for people with mild cognitive impairment (MCI) and dementia, which in recent years has also been developed for various IT platforms. In this study, we aim to evaluate the effectiveness of the cognitive rehabilitation software GRADIOR in a multi-centre, single-blinded randomised controlled trial with people with MCI and mild dementia. A total of 400 people with MCI and mild dementia will be randomly allocated to one of four groups. This trial will compare the cognitive rehabilitation treatment using the GRADIOR programme with a psychosocial stimulation intervention (PSS) using the ehcoBUTLER platform, with a combined treatment consisting of GRADIOR and ehcoBUTLER, and with a group receiving treatment as usual during a period of 1 year. The outcomes of this clinical trial will be to determine any relevant changes in cognition, mood, quality of life, activities of daily living and quality of patient-carer relationship after 4 months and 1 year of intervention in a cross-sectional group comparison. Participants will be followed-up for 1 year to investigate potential long-term effects of the conducted treatments. Current Controlled Trials ISRCTN, ID: 15742788 . Registered on 12 June 2017.

Annual variation in decomposition and insect succession at a periurban area of central Iberian Peninsula.

PubMed

Díaz-Aranda, Luisa M; Martín-Vega, Daniel; Gómez-Gómez, Aída; Cifrián, Blanca; Baz, Arturo

2018-05-01

The variation in decomposition and insect succession among the four seasons of one year was studied for the first time in a periurban area of central Spain. During the winter trial, the carcasses showed corification, a cadaveric preservation phenomenon which apparently leaded to a significant delay in decomposition processes. The composition of the insect fauna breeding on carcasses changed significantly between trials. Active decay was mainly driven by Calliphoridae (Diptera) larvae in every season except in winter trial, when larvae of Thanatophilus species (Coleoptera: Silphidae) were the main consumers of soft tissues. Advanced decay was characterized by the occurrence of Dermestidae, Silphidae, Cleridae, Nitidulidae (Coleoptera) and Piophilidae (Diptera) larvae. Differences in the species composition in comparison with other regions of the Iberian Peninsula were also observed. The current paper provides baseline and preliminary information on the insect succession on carrion in central Spain, as well as a starting point for further research on forensic entomology in this region. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Lubiprostone.

PubMed

McKeage, Kate; Plosker, Greg L; Siddiqui, M Asif A

2006-01-01

Lubiprostone (Amitiza) is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of the gastrointestinal epithelium, resulting in increased fluid secretion. In two pivotal, randomised, double-blind, multicentre phase III studies in patients with chronic idiopathic constipation, the frequency of spontaneous bowel movements (SBMs) was significantly greater in patients receiving lubiprostone 24microg twice daily than in those receiving placebo at each weekly timepoint throughout both 4-week studies (p < 0.05). At week 1 in one pivotal trial, the mean frequency of SBMs in the lubiprostone group was 5.9 per week compared with 4.0 per week in the placebo group (p < 0.0001) [baseline SBMs 1.3 and 1.5 per week]. Significantly greater improvements occurred with lubiprostone than placebo in the degree of straining, stool consistency and constipation severity (where reported) in both pivotal studies (p < 0.05 for all comparisons at all timepoints). Lubiprostone was generally well tolerated in clinical trials with no reports of treatment-related serious adverse events in pivotal trials. Nausea was the most common adverse event, occurring in up to 31% of patients receiving lubiprostone.

Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison

PubMed Central

Loke, Yoon K; Pradhan, Shiva; Yeong, Jessica Ka-yan; Kwok, Chun Shing

2014-01-01

Aims There are concerns regarding increased risk of acute coronary syndrome with dabigatran. We aimed to assess whether alternative treatment options such as rivaroxaban or apixaban carry a similar risk as compared with dabigatran. Methods We searched MEDLINE and EMBASE for randomized controlled trials of apixaban, dabigatran or rivaroxaban against control (placebo, heparin or vitamin K antagonist). We pooled odds ratios (OR) for adverse coronary events (acute coronary syndrome or myocardial infarction) using fixed effect meta-analysis and assessed heterogeneity with I2. We conducted adjusted indirect comparisons to compare risk of adverse coronary events with apixaban or rivaroxaban vs. dabigatran. Results Twenty-seven randomized controlled trials met the inclusion criteria. Dabigatran was associated with a significantly increased risk of adverse coronary events in pooled analysis of nine trials (OR 1.45, 95% CI 1.14, 1.86). There was no signal for coronary risk with apixaban from nine trials (pooled OR 0.89, 95% CI 0.78, 1.03) or rivaroxaban from nine trials (pooled OR 0.81, 95% CI 0.72, 0.93). Overall, adjusted indirect comparison suggested that both apixaban (OR 0.61, 95% CI 0.44, 0.85) and rivaroxaban (OR 0.54; 95% CI 0.39, 0.76) were associated with lower coronary risk than dabigatran. Restricting the indirect comparison to a vitamin K antagonist as a common control, yielded similar findings, OR 0.57 (95% CI 0.39, 0.85) for apixaban vs. dabigatran and 0.53 (95% CI 0.37, 0.77) for rivaroxaban vs. dabigatran. Conclusions There are significant differences in the comparative safety of apixaban, rivaroxaban and dabigatran with regards to acute coronary adverse events. PMID:24617578

Quantitative analysis of impact of awareness-raising activities on organic solid waste separation behaviour in Balikpapan City, Indonesia.

PubMed

Murase, Noriaki; Murayama, Takehiko; Nishikizawa, Shigeo; Sato, Yuriko

2017-10-01

Many cities in Indonesia are under pressure to reduce solid waste and dispose of it properly. In response to this pressure, the Japan International Cooperation Agency and the Indonesian Government have implemented a solid waste separation and collection project to reduce solid waste in the target area (810 households) of Balikpapan City. We used a cluster randomised controlled trial method to measure the impact of awareness-raising activities that were introduced by the project on residents' organic solid waste separation behaviour. The level of properly separated organic solid waste increased by 6.0% in areas that conducted awareness-raising activities. Meanwhile, the level decreased by 3.6% in areas that did not conduct similar activities. Therefore, in relative comparison, awareness-raising increased the level by 9.6%. A comparison among small communities in the target area confirmed that awareness-raising activities had a significant impact on organic solid waste separation. High frequencies of monitoring at waste stations and door-to-door visits by community members had a positive impact on organic solid waste separation. A correlation between the proximity of environmental volunteers' houses to waste stations and a high level of separation was also confirmed. The awareness-raising activities introduced by the project led to a significant increase in the separation of organic solid waste.

The Trial State Assessment: Prospects and Realities. The Third Report of the National Academy of Education Panel on the Evaluation of the NAEP Trial State Assessment: 1992 Trial State Assessment.

ERIC Educational Resources Information Center

National Academy of Education, Stanford, CA.

The National Academy of Education Panel is providing the intellectual leadership and coordination for an independent evaluation of the 1990 and 1992 Trial State Assessments (TSA) of the National Assessment of Educational Progress (NAEP). These instruments provide state-by-state comparisons of educational achievement, which is the first such use of…

Head-to-head randomized trials are mostly industry sponsored and almost always favor the industry sponsor.

PubMed

Flacco, Maria Elena; Manzoli, Lamberto; Boccia, Stefania; Capasso, Lorenzo; Aleksovska, Katina; Rosso, Annalisa; Scaioli, Giacomo; De Vito, Corrado; Siliquini, Roberta; Villari, Paolo; Ioannidis, John P A

2015-07-01

To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results. From a 50% random sample of the randomized controlled trials (RCTs) published in journals indexed in PubMed during 2011, we selected the trials with ≥ 100 participants, evaluating the efficacy and safety of drugs, biologics, and medical devices through a head-to-head comparison. We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only three involved truly antagonistic comparisons. Industry-sponsored trials were larger, more commonly registered, used more frequently noninferiority/equivalence designs, had higher citation impact, and were more likely to have "favorable" results (superiority or noninferiority/equivalence for the experimental treatment) than nonindustry-sponsored trials. Industry funding [odds ratio (OR) 2.8; 95% confidence interval (CI): 1.6, 4.7] and noninferiority/equivalence designs (OR 3.2; 95% CI: 1.5, 6.6), but not sample size, were strongly associated with "favorable" findings. Fifty-five of the 57 (96.5%) industry-funded noninferiority/equivalence trials got desirable "favorable" results. The literature of head-to-head RCTs is dominated by the industry. Industry-sponsored comparative assessments systematically yield favorable results for the sponsors, even more so when noninferiority designs are involved. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Long-term prophylaxis in hereditary angio-oedema: a systematic review

PubMed Central

Casazza, Giovanni; Bossi, Ilaria; Duca, Piergiorgio; Cicardi, Marco

2012-01-01

Objective To systematically review the evidence regarding long-term prophylaxis in the prevention or reduction of attacks in hereditary angio-oedema (HAE). Design Systematic review and meta-analysis. Data sources Electronic databases were searched up to April 2011. Two reviewers selected the studies and extracted the study data, patient characteristics and outcomes of interest. Eligibility criteria for selected studies Controlled trials for HAE prophylaxis. Results 7 studies were included, for a total of 73 patients and 587 HAE attacks. Due to the paucity of studies, a meta-analysis was not possible. Since two studies did not report the number of HAE attacks, five studies (52 patients) were finally included in the summary analysis. Four classes of drugs with at least one controlled trial have been proposed for HAE prophylaxis. All those drugs, except heparin, were found to be more effective than placebo. In the absence of direct comparisons, the relative efficacies of these drugs were determined by calculating a RR of attacks (drug vs placebo). The results were as follows: danazol (RR=0.023, 95% CI 0.003 to 0.162), methyltestosterone (RR=0.054, 95% CI 0.013 to 0.163), ɛ-aminocaproic acid (RR=0.095, 95% CI 0.025 to 0.356), tranexamic acid (RR=0.308, 95% CI 0.195 to 0.479) and C1-INH 0.491 (95% CI 0.395 to 0.607). Conclusions Few trials have evaluated the benefits of HAE prophylaxis, and all drugs but heparin seem to be effective in this setting. Since there are no direct comparisons of HAE drugs, it was not possible to draw definitive conclusions on the most effective one. Thus, to accumulate evidence for HAE prophylaxis, further studies are needed that consider the dose–efficacy relationship and include a head-to-head comparison between drugs, with the active group, rather than placebo, as the control. PMID:22786946

Statistical analysis plan for evaluating low- vs. standard-dose alteplase in the ENhanced Control of Hypertension and Thrombolysis strokE stuDy (ENCHANTED).

PubMed

Anderson, Craig S; Woodward, Mark; Arima, Hisatomi; Chen, Xiaoying; Lindley, Richard I; Wang, Xia; Chalmers, John

2015-12-01

The ENhanced Control of Hypertension And Thrombolysis strokE stuDy trial is a 2 × 2 quasi-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial that is evaluating in thrombolysis-eligible acute ischemic stroke patients whether: (1) low-dose (0·6 mg/kg body weight) intravenous alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage compared with standard-dose (0·9 mg/kg body weight) intravenous alteplase; and (2) early intensive blood pressure lowering (systolic target 130-140 mmHg) has superior efficacy and lower risk of any intracerebral hemorrhage compared with guideline-recommended blood pressure control (systolic target <180 mmHg). To outline in detail the predetermined statistical analysis plan for the 'alteplase dose arm' of the study. All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be classified, and for each item, appropriate descriptive statistical analyses are planned with appropriate comparisons made between randomized groups. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. A statistical analysis plan was developed for the results of the alteplase dose arm of the study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. We have developed a predetermined statistical analysis plan for the ENhanced Control of Hypertension And Thrombolysis strokE stuDy alteplase dose arm which is to be followed to avoid analysis bias arising from prior knowledge of the study findings. © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Slipping during side-step cutting: anticipatory effects and familiarization.

PubMed

Oliveira, Anderson Souza Castelo; Silva, Priscila Brito; Lund, Morten Enemark; Farina, Dario; Kersting, Uwe Gustav

2014-04-01

The aim of the present study was to verify whether the expectation of perturbations while performing side-step cutting manoeuvres influences lower limb EMG activity, heel kinematics and ground reaction forces. Eighteen healthy men performed two sets of 90° side-step cutting manoeuvres. In the first set, 10 unperturbed trials (Base) were performed while stepping over a moveable force platform. In the second set, subjects were informed about the random possibility of perturbations to balance throughout 32 trials, of which eight were perturbed (Pert, 10cm translation triggered at initial contact), and the others were "catch" trials (Catch). Center of mass velocity (CoMVEL), heel acceleration (HAC), ground reaction forces (GRF) and surface electromyography (EMG) from lower limb and trunk muscles were recorded for each trial. Surface EMG was analyzed prior to initial contact (PRE), during load acceptance (LA) and propulsion (PRP) periods of the stance phase. In addition, hamstrings-quadriceps co-contraction ratios (CCR) were calculated for these time-windows. The results showed no changes in CoMVEL, HAC, peak GRF and surface EMG PRE among conditions. However, during LA, there were increases in tibialis anterior EMG (30-50%) concomitant to reduced EMG for quadriceps muscles, gluteus and rectus abdominis for Catch and Pert conditions (15-40%). In addition, quadriceps EMG was still reduced during PRP (p<.05). Consequently, CCR was greater for Catch and Pert in comparison to Base (p<.05). These results suggest that there is modulation of muscle activity towards anticipating potential instability in the lower limb joints and assure safety to complete the task. Copyright © 2014. Published by Elsevier B.V.

Does the Method of Weight Loss Effect Long-Term Changes in Weight, Body Composition or Chronic Disease Risk Factors in Overweight or Obese Adults? A Systematic Review

PubMed Central

Washburn, Richard A.; Szabo, Amanda N.; Lambourne, Kate; Willis, Erik A.; Ptomey, Lauren T.; Honas, Jeffery J.; Herrmann, Stephen D.; Donnelly, Joseph E.

2014-01-01

Background Differences in biological changes from weight loss by energy restriction and/or exercise may be associated with differences in long-term weight loss/regain. Objective To assess the effect of weight loss method on long-term changes in weight, body composition and chronic disease risk factors. Data Sources PubMed and Embase were searched (January 1990-October 2013) for studies with data on the effect of energy restriction, exercise (aerobic and resistance) on long-term weight loss. Twenty articles were included in this review. Study Eligibility Criteria Primary source, peer reviewed randomized trials published in English with an active weight loss period of >6 months, or active weight loss with a follow-up period of any duration, conducted in overweight or obese adults were included. Study Appraisal and Synthesis Methods Considerable heterogeneity across trials existed for important study parameters, therefore a meta-analysis was considered inappropriate. Results were synthesized and grouped by comparisons (e.g. diet vs. aerobic exercise, diet vs. diet + aerobic exercise etc.) and study design (long-term or weight loss/follow-up). Results Forty percent of trials reported significantly greater long-term weight loss with diet compared with aerobic exercise, while results for differences in weight regain were inconclusive. Diet+aerobic exercise resulted in significantly greater weight loss than diet alone in 50% of trials. However, weight regain (∼55% of loss) was similar in diet and diet+aerobic exercise groups. Fat-free mass tended to be preserved when interventions included exercise. PMID:25333384

Increased Intra-Participant Variability in Children with Autistic Spectrum Disorders: Evidence from Single-Trial Analysis of Evoked EEG

PubMed Central

Milne, Elizabeth

2011-01-01

Intra-participant variability in clinical conditions such as autistic spectrum disorder (ASD) is an important indicator of pathophysiological processing. The data reported here illustrate that trial-by-trial variability can be reliably measured from EEG, and that intra-participant EEG variability is significantly greater in those with ASD than in neuro-typical matched controls. EEG recorded at the scalp is a linear mixture of activity arising from muscle artifacts and numerous concurrent brain processes. To minimize these additional sources of variability, EEG data were subjected to two different methods of spatial filtering. (i) The data were decomposed using infomax independent component analysis, a method of blind source separation which un-mixes the EEG signal into components with maximally independent time-courses, and (ii) a surface Laplacian transform was performed (current source density interpolation) in order to reduce the effects of volume conduction. Data are presented from 13 high functioning adolescents with ASD without co-morbid ADHD, and 12 neuro-typical age-, IQ-, and gender-matched controls. Comparison of variability between the ASD and neuro-typical groups indicated that intra-participant variability of P1 latency and P1 amplitude was greater in the participants with ASD, and inter-trial α-band phase coherence was lower in the participants with ASD. These data support the suggestion that individuals with ASD are less able to synchronize the activity of stimulus-related cell assemblies than neuro-typical individuals, and provide empirical evidence in support of theories of increased neural noise in ASD. PMID:21716921

Physical activity and trial-by-trial adjustments of response conflict.

PubMed

Kamijo, Keita; Takeda, Yuji

2013-08-01

The relationship of physical activity to trial-by-trial adjustments of response conflict was assessed using behavioral task performance, the N2 event-related brain potential component, and phase-locking values (PLVs) in a lower gamma band during a perceptual conflict task. Nineteen physically active and 19 inactive young adults (mean age = 21.3 years) performed a Navon task, using a global letter made up of local letters of either the same kind (congruent trials) or a different kind (incongruent trials). Findings revealed that active individuals exhibited smaller N2 amplitudes and greater PLVs on incongruent trials that were preceded by incongruent trials compared with those preceded by congruent trials. Such phenomena were not observed for inactive individuals. These results suggest that greater physical activity is associated with larger trial-by-trial adjustments of response conflict, which we attribute to upregulation of top-down cognitive control and reductions in response conflict.

Comparative efficacy and safety of tofacitinib, with or without methotrexate, in patients with active rheumatoid arthritis: a Bayesian network meta-analysis of randomized controlled trials.

PubMed

Lee, Young Ho; Bae, Sang-Cheol; Song, Gwan Gyu

2015-12-01

This study aimed to assess the relative efficacy and safety of tofacitinib 5 and 10 mg twice daily, or in combination with methotrexate (MTX), in patients with active RA. Randomized controlled trials (RCTs) examining the efficacy and safety of tofacitinib in patients with active RA were included in this network meta-analysis. We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from the RCTs. Ten RCTs including 4867 patients met the inclusion criteria. There were 21 pairwise comparisons including 11 direct comparisons of seven interventions. The ACR20 response rate was significantly higher in the tofacitinib 10 mg + MTX group than in the placebo and MTX groups (OR 7.56, 95 % credible interval (CrI) 3.07-21.16; OR 3.67, 95 % CrI 2.60-5.71, respectively). Ranking probabilities based on the surface under the cumulative ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX had the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.9254), followed by tofacitinib 5 mg + MTX (SUCRA = 0.7156), adalimumab 40 mg + MTX (SUCRA = 0.6097), tofacitinib 10 mg (SUCRA = 0.5984), tofacitinib 5 mg (SUCRA = 0.4749), MTX (SUCRA = 0.1674), and placebo (SUCRA = 0.0086). In contrast, the safety based on the number of withdrawals due to adverse events did not differ significantly among the seven interventions. Tofacitinib, at dosages 5 and 10 mg twice daily, in combination with MTX, was the most efficacious intervention for active RA and was not associated with a significant risk for withdrawals due to adverse events.

Delayed matching to two-picture samples by individuals with and without disabilities: an analysis of the role of naming.

PubMed

Gutowski, Stanley J; Stromer, Robert

2003-01-01

Delayed matching to complex, two-picture samples (e.g., cat-dog) may be improved when the samples occasion differential verbal behavior. In Experiment 1, individuals with mental retardation matched picture comparisons to identical single-picture samples or to two-picture samples, one of which was identical to a comparison. Accuracy scores were typically high on single-picture trials under both simultaneous and delayed matching conditions. Scores on two-picture trials were also high during the simultaneous condition but were lower during the delay condition. However, scores improved on delayed two-picture trials when each of the sample pictures was named aloud before comparison responding. Experiment 2 replicated these results with preschoolers with typical development and a youth with mental retardation. Sample naming also improved the preschoolers' matching when the samples were pairs of spoken names and the correct comparison picture matched one of the names. Collectively, the participants could produce the verbal behavior that might have improved performance, but typically did not do so unless the procedure required it. The success of the naming intervention recommends it for improving the observing and remembering of multiple elements of complex instructional stimuli.

Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors.

PubMed

Gladman, Dafna; Rigby, William; Azevedo, Valderilio F; Behrens, Frank; Blanco, Ricardo; Kaszuba, Andrzej; Kudlacz, Elizabeth; Wang, Cunshan; Menon, Sujatha; Hendrikx, Thijs; Kanik, Keith S

2017-10-19

Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors. In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis. At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib. In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).

A randomized controlled trial comparing 2 interventions for visual field loss with standard occupational therapy during inpatient stroke rehabilitation.

PubMed

Mödden, Claudia; Behrens, Marion; Damke, Iris; Eilers, Norbert; Kastrup, Andreas; Hildebrandt, Helmut

2012-06-01

Compensatory and restorative treatments have been developed to improve visual field defects after stroke. However, no controlled trials have compared these interventions with standard occupational therapy (OT). A total of 45 stroke participants with visual field defect admitted for inpatient rehabilitation were randomized to restorative computerized training (RT) using computer-based stimulation of border areas of their visual field defects or to a computer-based compensatory therapy (CT) teaching a visual search strategy. OT, in which different compensation strategies were used to train for activities of daily living, served as standard treatment for the active control group. Each treatment group received 15 single sessions of 30 minutes distributed over 3 weeks. The primary outcome measures were visual field expansion for RT, visual search performance for CT, and reading performance for both treatments. Visual conjunction search, alertness, and the Barthel Index were secondary outcomes. Compared with OT, CT resulted in a better visual search performance, and RT did not result in a larger expansion of the visual field. Intragroup pre-post comparisons demonstrated that CT improved all defined outcome parameters and RT several, whereas OT only improved one. CT improved functional deficits after visual field loss compared with standard OT and may be the intervention of choice during inpatient rehabilitation. A larger trial that includes lesion location in the analysis is recommended.

Real medical benefit assessed by indirect comparison.

PubMed

Falissard, Bruno; Zylberman, Myriam; Cucherat, Michel; Izard, Valérie; Meyer, François

2009-01-01

Frequently, in data packages submitted for Marketing Approval to the CHMP, there is a lack of relevant head-to-head comparisons of medicinal products that could enable national authorities responsible for the approval of reimbursement to assess the Added Therapeutic Value (ASMR) of new clinical entities or line extensions of existing therapies.Indirect or mixed treatment comparisons (MTC) are methods stemming from the field of meta-analysis that have been designed to tackle this problem. Adjusted indirect comparisons, meta-regressions, mixed models, Bayesian network analyses pool results of randomised controlled trials (RCTs), enabling a quantitative synthesis.The REAL procedure, recently developed by the HAS (French National Authority for Health), is a mixture of an MTC and effect model based on expert opinions. It is intended to translate the efficacy observed in the trials into effectiveness expected in day-to-day clinical practice in France.

Therapeutic ultrasound for acute ankle sprains.

PubMed

van den Bekerom, Michel Pj; van der Windt, Daniëlle Awm; Ter Riet, Gerben; van der Heijden, Geert J; Bouter, Lex M

2011-06-15

Ultrasound is used in the treatment of a wide variety of musculoskeletal disorders, which include acute ankle sprains. This is an update of a Cochrane review first published in 1999, and previously updated in 2004. To evaluate the effects of ultrasound therapy in the treatment of acute ankle sprains. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (September 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 3), MEDLINE (1966 to September 2010), EMBASE (1983 to September 2010), CINAHL (1982 to 2004), and PEDro - the Physiotherapy Evidence Database (accessed 01/06/09). We also searched the Cochrane Rehabilitation and Related Therapies Field database, reference lists of articles, and contacted colleagues.The WHO International Clinical Trials Registry Platform was searched for ongoing trials. Randomised or quasi-randomised trials were included if the following conditions were met: at least one study group was treated with therapeutic ultrasound; participants had acute lateral ankle sprains; and outcome measures included general improvement, pain, swelling, functional disability, or range of motion. Two authors independently performed study selection, and assessed the risk of bias and extracted data. Risk ratios and risk differences together with 95% confidence intervals were calculated for dichotomous outcomes and mean differences together with 95% confidence intervals for continuous outcome measures. Limited pooling of data was undertaken where there was clinical homogeneity in terms of participants, treatments, outcomes, and follow-up time points. Six trials were included, involving 606 participants. Five trials included comparisons of ultrasound therapy with sham ultrasound; and three trials included single comparisons of ultrasound with three other treatments. The assessment of risk of bias was hampered by poor reporting of trial methods and results. None of the five placebo-controlled trials (sham ultrasound) demonstrated statistically significant differences between true and sham ultrasound therapy for any outcome measure at one to four weeks of follow-up. The pooled risk ratio for general improvement at one week was 1.04 (random-effects model, 95% confidence interval 0.92 to 1.17) for active versus sham ultrasound. The differences between intervention groups were generally small, between zero and six per cent, for most dichotomous outcomes. The evidence from the five small placebo-controlled trials included in this review does not support the use of ultrasound in the treatment of acute ankle sprains. The potential treatment effects of ultrasound appear to be generally small and of probably of limited clinical importance, especially in the context of the usually short-term recovery period for these injuries. However, the available evidence is insufficient to rule out the possibility that there is an optimal dosage schedule for ultrasound therapy that may be of benefit.

Neural circuitry of emotional and cognitive conflict revealed through facial expressions.

PubMed

Chiew, Kimberly S; Braver, Todd S

2011-03-09

Neural systems underlying conflict processing have been well studied in the cognitive realm, but the extent to which these overlap with those underlying emotional conflict processing remains unclear. A novel adaptation of the AX Continuous Performance Task (AX-CPT), a stimulus-response incompatibility paradigm, was examined that permits close comparison of emotional and cognitive conflict conditions, through the use of affectively-valenced facial expressions as the response modality. Brain activity was monitored with functional magnetic resonance imaging (fMRI) during performance of the emotional AX-CPT. Emotional conflict was manipulated on a trial-by-trial basis, by requiring contextually pre-cued facial expressions to emotional probe stimuli (IAPS images) that were either affectively compatible (low-conflict) or incompatible (high-conflict). The emotion condition was contrasted against a matched cognitive condition that was identical in all respects, except that probe stimuli were emotionally neutral. Components of the brain cognitive control network, including dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC), showed conflict-related activation increases in both conditions, but with higher activity during emotion conditions. In contrast, emotion conflict effects were not found in regions associated with affective processing, such as rostral ACC. These activation patterns provide evidence for a domain-general neural system that is active for both emotional and cognitive conflict processing. In line with previous behavioural evidence, greatest activity in these brain regions occurred when both emotional and cognitive influences additively combined to produce increased interference.

Space-by-Time Modular Decomposition Effectively Describes Whole-Body Muscle Activity During Upright Reaching in Various Directions

PubMed Central

Hilt, Pauline M.; Delis, Ioannis; Pozzo, Thierry; Berret, Bastien

2018-01-01

The modular control hypothesis suggests that motor commands are built from precoded modules whose specific combined recruitment can allow the performance of virtually any motor task. Despite considerable experimental support, this hypothesis remains tentative as classical findings of reduced dimensionality in muscle activity may also result from other constraints (biomechanical couplings, data averaging or low dimensionality of motor tasks). Here we assessed the effectiveness of modularity in describing muscle activity in a comprehensive experiment comprising 72 distinct point-to-point whole-body movements during which the activity of 30 muscles was recorded. To identify invariant modules of a temporal and spatial nature, we used a space-by-time decomposition of muscle activity that has been shown to encompass classical modularity models. To examine the decompositions, we focused not only on the amount of variance they explained but also on whether the task performed on each trial could be decoded from the single-trial activations of modules. For the sake of comparison, we confronted these scores to the scores obtained from alternative non-modular descriptions of the muscle data. We found that the space-by-time decomposition was effective in terms of data approximation and task discrimination at comparable reduction of dimensionality. These findings show that few spatial and temporal modules give a compact yet approximate representation of muscle patterns carrying nearly all task-relevant information for a variety of whole-body reaching movements. PMID:29666576

Neural Circuitry of Emotional and Cognitive Conflict Revealed through Facial Expressions

PubMed Central

Chiew, Kimberly S.; Braver, Todd S.

2011-01-01

Background Neural systems underlying conflict processing have been well studied in the cognitive realm, but the extent to which these overlap with those underlying emotional conflict processing remains unclear. A novel adaptation of the AX Continuous Performance Task (AX-CPT), a stimulus-response incompatibility paradigm, was examined that permits close comparison of emotional and cognitive conflict conditions, through the use of affectively-valenced facial expressions as the response modality. Methodology/Principal Findings Brain activity was monitored with functional magnetic resonance imaging (fMRI) during performance of the emotional AX-CPT. Emotional conflict was manipulated on a trial-by-trial basis, by requiring contextually pre-cued facial expressions to emotional probe stimuli (IAPS images) that were either affectively compatible (low-conflict) or incompatible (high-conflict). The emotion condition was contrasted against a matched cognitive condition that was identical in all respects, except that probe stimuli were emotionally neutral. Components of the brain cognitive control network, including dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC), showed conflict-related activation increases in both conditions, but with higher activity during emotion conditions. In contrast, emotion conflict effects were not found in regions associated with affective processing, such as rostral ACC. Conclusions/Significance These activation patterns provide evidence for a domain-general neural system that is active for both emotional and cognitive conflict processing. In line with previous behavioural evidence, greatest activity in these brain regions occurred when both emotional and cognitive influences additively combined to produce increased interference. PMID:21408006

Evaluation of platelet adhesion and activation on polymers: Round-robin study to assess inter-center variability.

PubMed

Braune, S; Sperling, C; Maitz, M F; Steinseifer, U; Clauser, J; Hiebl, B; Krajewski, S; Wendel, H P; Jung, F

2017-10-01

The regulatory agencies provide recommendations rather than protocols or standard operation procedures for the hemocompatibility evaluation of novel materials e.g. for cardiovascular applications. Thus, there is a lack of specifications with regard to test setups and procedures. As a consequence, laboratories worldwide perform in vitro assays under substantially different test conditions, so that inter-laboratory and inter-study comparisons are impossible. Here, we report about a prospective, randomized and double-blind multicenter trial which demonstrates that standardization of in vitro test protocols allows a reproducible assessment of platelet adhesion and activation from fresh human platelet rich plasma as possible indicators of the thrombogenicity of cardiovascular implants. Standardization of the reported static in vitro setup resulted in a laboratory independent scoring of the following materials: poly(dimethyl siloxane) (PDMS), poly(ethylene terephthalate) (PET) and poly(tetrafluoro ethylene) (PTFE). The results of this in vitro study provide evidence that inter-laboratory and inter-study comparisons can be achieved for the evaluation of the adhesion and activation of platelets on blood-contacting biomaterials by stringent standardization of test protocols. Copyright © 2017 Elsevier B.V. All rights reserved.

Promoting early presentation of breast cancer in older women: sustained effect of an intervention to promote breast cancer awareness in routine clinical practice.

PubMed

Dodd, Rachael H; Forster, Alice S; Sellars, Sarah; Patnick, Julietta; Ramirez, Amanda J; Forbes, Lindsay J L

2017-06-05

Older women have poorer survival from breast cancer, which may be at least partly due to poor breast cancer awareness leading to delayed presentation and more advanced stage at diagnosis. In a randomised trial, an intervention to promote early presentation of breast cancer in older women increased breast cancer awareness at 1 year compared with usual care (24 versus 4%). We examined its effectiveness in routine clinical practice. We piloted the intervention delivered by practising health professionals to women aged about 70 in four breast screening services. We measured the effect on breast cancer awareness at 1 year compared with comparison services, where women did not receive the intervention. At 1 year, 25% of women in pilot services were breast cancer aware compared with 4% in comparison services (p = 0.001). The components of breast cancer awareness were knowledge of breast cancer non-lump symptoms (pilot: 63% vs comparison: 82% at 1 year; OR = 2.56, 95% CI 1.92-3.42), knowledge of age related risk (pilot: 8% vs comparison: 36% at 1 year; OR = 5.56, 95% CI 4.0-7.74) and reported breast checking (pilot: 70% vs comparison: 78% at 1 year; OR = 1.49, 95% CI 1.13-1.96). The intervention may be as effective in routine clinical practice as in a randomised controlled trial. This intervention has the potential to reduce patient delay in the diagnosis of breast cancer in older women. The PEP trial was registered with the International Standard Registered Clinical/soCial sTudy Number (ISRCTN) as a clinical trial ( ISRCTN31994827 ) on 3rd October 2007.

A comparison of two worlds: How does Bayes hold up to the status quo for the analysis of clinical trials?

PubMed

Pressman, Alice R; Avins, Andrew L; Hubbard, Alan; Satariano, William A

2011-07-01

There is a paucity of literature comparing Bayesian analytic techniques with traditional approaches for analyzing clinical trials using real trial data. We compared Bayesian and frequentist group sequential methods using data from two published clinical trials. We chose two widely accepted frequentist rules, O'Brien-Fleming and Lan-DeMets, and conjugate Bayesian priors. Using the nonparametric bootstrap, we estimated a sampling distribution of stopping times for each method. Because current practice dictates the preservation of an experiment-wise false positive rate (Type I error), we approximated these error rates for our Bayesian and frequentist analyses with the posterior probability of detecting an effect in a simulated null sample. Thus for the data-generated distribution represented by these trials, we were able to compare the relative performance of these techniques. No final outcomes differed from those of the original trials. However, the timing of trial termination differed substantially by method and varied by trial. For one trial, group sequential designs of either type dictated early stopping of the study. In the other, stopping times were dependent upon the choice of spending function and prior distribution. Results indicate that trialists ought to consider Bayesian methods in addition to traditional approaches for analysis of clinical trials. Though findings from this small sample did not demonstrate either method to consistently outperform the other, they did suggest the need to replicate these comparisons using data from varied clinical trials in order to determine the conditions under which the different methods would be most efficient. Copyright © 2011 Elsevier Inc. All rights reserved.

A comparison of two worlds: How does Bayes hold up to the status quo for the analysis of clinical trials?

PubMed Central

Pressman, Alice R.; Avins, Andrew L.; Hubbard, Alan; Satariano, William A.

2014-01-01

Background There is a paucity of literature comparing Bayesian analytic techniques with traditional approaches for analyzing clinical trials using real trial data. Methods We compared Bayesian and frequentist group sequential methods using data from two published clinical trials. We chose two widely accepted frequentist rules, O'Brien–Fleming and Lan–DeMets, and conjugate Bayesian priors. Using the nonparametric bootstrap, we estimated a sampling distribution of stopping times for each method. Because current practice dictates the preservation of an experiment-wise false positive rate (Type I error), we approximated these error rates for our Bayesian and frequentist analyses with the posterior probability of detecting an effect in a simulated null sample. Thus for the data-generated distribution represented by these trials, we were able to compare the relative performance of these techniques. Results No final outcomes differed from those of the original trials. However, the timing of trial termination differed substantially by method and varied by trial. For one trial, group sequential designs of either type dictated early stopping of the study. In the other, stopping times were dependent upon the choice of spending function and prior distribution. Conclusions Results indicate that trialists ought to consider Bayesian methods in addition to traditional approaches for analysis of clinical trials. Though findings from this small sample did not demonstrate either method to consistently outperform the other, they did suggest the need to replicate these comparisons using data from varied clinical trials in order to determine the conditions under which the different methods would be most efficient. PMID:21453792

Fixed or removable function appliances for Class II malocclusions.

PubMed

Madurantakam, Parthasarathy

2016-06-01

Data sourcesEmbase, Cochrane Central Register of Controlled Trials, Medline (Pubmed), Web of Science, Google Scholar, Scopus, LILACS database and bibliographies of clinical trials encountered during search. There was no restriction on language or date during search.Study selectionRandomised Controlled Trials (RCTs) and Controlled Clinical Trials (CCT) in patients with Class II malocclusions that compared at least one fixed functional appliance with at least one removable functional appliance (RFA) in children below 16 years of age. Primary outcomes were clinical and lateral cephalometric measurements and the duration of treatment. Secondary outcomes included patient experiences of treatment, quality of life measures and harms arising during treatment as well as costs of both treatments.Data extraction and synthesisThe titles and abstracts of all studies identified through the search were assessed independently and in duplicate by two review authors. Disagreements about included studies were resolved through discussion with the third author. Heterogeneity was assessed using customised forms and risk of bias using a Cochrane Collaboration tool. A meta-analysis was planned for studies at low risk of bias with similar comparisons reporting the same outcome.ResultsTwo RCTs and two CCTs that met the inclusion/exclusion criteria were included in the final analysis. Risk of bias assessment indicated three trials were at high risk while one was unclear. Consequently, the included trials were deemed to be inappropriate for meta-analysis (MA).Two studies with 282 participants evaluated Twin Block with fixed Herbst appliance and reported significant improvements in anterior-posterior skeletal discrepancy, mandibular length and reduction of overjet with both appliances. While one study reported significantly shorter treatment duration in Herbst appliance, the other study did not find any difference. Herbst appliance had better compliance, less dropouts but more emergency visits.One trial that compared activator appliance with Twin Force Bite Corrector found significantly shorter time with the fixed appliance. However, effective length and sagittal positioning of the mandible was not different between the groups.One trial comparing activator with Forsus FRZ reported enhanced mandibular growth and restrained maxillary growth with both the appliances. While activator appliance was associated with increased posterior facial height, Forsus significantly rotated the occlusal plane.ConclusionsLimited available evidence indicates that both fixed and removable functional appliances are effective in reducing overjet in growing children. However, there is insufficient evidence to differentiate between the two types with respect to biological (skeletal and dental) effects or patient experiences.

Reduced Cortisol Metabolism during Critical Illness

PubMed Central

Boonen, Eva; Vervenne, Hilke; Meersseman, Philippe; Andrew, Ruth; Mortier, Leen; Declercq, Peter E.; Vanwijngaerden, Yoo-Mee; Spriet, Isabel; Wouters, Pieter J.; Perre, Sarah Vander; Langouche, Lies; Vanhorebeek, Ilse; Walker, Brian R.; Van den Berghe, Greet

2015-01-01

BACKGROUND Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic–pituitary–adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. METHODS In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. RESULTS Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P<0.001 for both comparisons). Cortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (P<0.001). Impaired cortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). CONCLUSIONS During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.) PMID:23506003

Effect of completion-time windows in the analysis of health-related quality of life outcomes in cancer patients

PubMed Central

Ediebah, D. E.; Coens, C.; Maringwa, J. T.; Quinten, C.; Zikos, E.; Ringash, J.; King, M.; Gotay, C.; Flechtner, H.-H.; Schmucker von Koch, J.; Weis, J.; Smit, E. F.; Köhne, C.-H.; Bottomley, A.

2013-01-01

Background We examined if cancer patients' health-related quality of life (HRQoL) scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 are affected by the specific time point, before or during treatment, at which the questionnaire is completed, and whether this could bias the overall treatment comparison analyses. Patients and methods A ‘completion-time window’ variable was created on three closed EORTC randomised control trials in lung (non-small cell lung cancer, NSCLC) and colorectal cancer (CRC) to indicate when the QLQ-30 was completed relative to chemotherapy cycle dates, defined as ‘before’, ‘on’ and ‘after’. HRQoL mean scores were calculated using a linear mixed model. Results Statistically significant differences (P < 0.05) were observed on 6 and 5 scales for ‘on’ and ‘after’ comparisons in the NSCLC and two-group CRC trial, respectively. As for the three-group CRC trial, several statistical differences were observed in the ‘before’ to ‘on’ and the ‘on’ to ‘after’ comparisons. For all three trials, including the ‘completion-time window’ variable in the model resulted in a better fit, but no substantial changes in the treatment effects were noted. Conclusions We showed that considering the exact timing of completion within specified windows resulted in statistical and potentially clinically significant differences, but it did not alter the conclusions of treatment comparison in these studies. PMID:22935549

Ophthalmic randomized controlled trials reports: the statement of the hypothesis.

PubMed

Lee, Chun Fan; Cheng, Andy Chi On; Fong, Daniel Yee Tak

2014-01-01

To evaluate whether the ophthalmic randomized controlled trials (RCTs) were designed properly, their hypotheses stated clearly, and their conclusions drawn correctly. A systematic review of 206 ophthalmic RCTs. The objective statement, methods, and results sections and the conclusions of RCTs published in 4 major general clinical ophthalmology journals from 2009 through 2011 were assessed. The clinical objective and specific hypothesis were the main outcome measures. The clinical objective of the trial was presented in 199 (96.6%) studies and the hypothesis was specified explicitly in 56 (27.2%) studies. One hundred ninety (92.2%) studies tested superiority. Among them, 17 (8.3%) studies comparing 2 or more active treatments concluded equal or similar effectiveness between the 2 arms after obtaining insignificant results. There were 5 noninferiority studies and 4 equivalence studies. How the treatments were compared was not mentioned in 1 of the noninferiority studies. Two of the equivalence studies did not specify the equivalence margin and used tests for detecting difference rather than confirming equivalence. The clinical objective commonly was stated, but the prospectively defined hypothesis tended to be understated in ophthalmic RCTs. Superiority was the most common type of comparison. Conclusions made in some of them with negative results were not consistent with the hypothesis, indicating that noninferiority or equivalence may be a more appropriate design. Flaws were common in the noninferiority and equivalence studies. Future ophthalmic researchers should choose the type of comparison carefully, specify the hypothesis clearly, and draw conclusions that are consistent with the hypothesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Systematic review: conservative treatments for secondary lymphedema

PubMed Central

2012-01-01

Background Several conservative (i.e., nonpharmacologic, nonsurgical) treatments exist for secondary lymphedema. The optimal treatment is unknown. We examined the effectiveness of conservative treatments for secondary lymphedema, as well as harms related to these treatments. Methods We searched MEDLINE®, EMBASE®, Cochrane Central Register of Controlled Trials®, AMED, and CINAHL from 1990 to January 19, 2010. We obtained English- and non-English-language randomized controlled trials or observational studies (with comparison groups) that reported primary effectiveness data on conservative treatments for secondary lymphedema. For English-language studies, we extracted data in tabular form and summarized the tables descriptively. For non-English-language studies, we summarized the results descriptively and discussed similarities with the English-language studies. Results Thirty-six English-language and eight non-English-language studies were included in the review. Most of these studies involved upper-limb lymphedema secondary to breast cancer. Despite lymphedema's chronicity, lengths of follow-up in most studies were under 6 months. Many trial reports contained inadequate descriptions of randomization, blinding, and methods to assess harms. Most observational studies did not control for confounding. Many studies showed that active treatments reduced the size of lymphatic limbs, although extensive between-study heterogeneity in areas such as treatment comparisons and protocols, and outcome measures, prevented us from assessing whether any one treatment was superior. This heterogeneity also precluded us from statistically pooling results. Harms were rare (< 1% incidence) and mostly minor (e.g., headache, arm pain). Conclusions The literature contains no evidence to suggest the most effective treatment for secondary lymphedema. Harms are few and unlikely to cause major clinical problems. PMID:22216837

Effects of a Program to Promote High Quality Parenting by Divorced and Separated Fathers.

PubMed

Sandler, Irwin; Gunn, Heather; Mazza, Gina; Tein, Jenn-Yun; Wolchik, Sharlene; Berkel, Cady; Jones, Sarah; Porter, Michele

2018-05-01

This paper reports on the effects on parenting and on children's mental health problems and competencies from a randomized trial of a parenting program for divorced and separated fathers. The program, New Beginnings Program-Dads (NBP-Dads), includes ten group sessions (plus two phone sessions) which promote parenting skills to increase positive interactions with children, improve father-child communication, use of effective discipline strategies, and skills to protect children from exposure to interparental conflict. The program was adapted from the New Beginnings Program, which has been tested in two randomized trials with divorced mothers and shown to strengthen mothers' parenting and improve long-term outcomes for children (Wolchik et al. 2007). Fathers were randomly assigned to receive either NBP-Dads or a 2-session active comparison program. The sample consisted of 384 fathers (201 NBP-Dads, 183 comparisons) and their children. Assessments using father, youth, and teacher reports were conducted at pretest, posttest, and 10-month follow-up. Results indicated positive effects of NBP-Dads to strengthen parenting as reported by fathers and youth at posttest and 10-month follow-up. Program effects to reduce child internalizing problems and increase social competence were found at 10 months. Many of the program effects were moderated by baseline level of the variable, child age, gender, and father ethnicity. This is the first randomized trial to find significant effects to strengthen father parenting following divorce. In view of recent changes in family courts to allot fathers increasing amounts of parenting time following divorce, the results have significant implications for improving outcomes for children from divorced families.

Type I error probabilities based on design-stage strategies with applications to noninferiority trials.

PubMed

Rothmann, Mark

2005-01-01

When testing the equality of means from two different populations, a t-test or large sample normal test tend to be performed. For these tests, when the sample size or design for the second sample is dependent on the results of the first sample, the type I error probability is altered for each specific possibility in the null hypothesis. We will examine the impact on the type I error probabilities for two confidence interval procedures and procedures using test statistics when the design for the second sample or experiment is dependent on the results from the first sample or experiment (or series of experiments). Ways for controlling a desired maximum type I error probability or a desired type I error rate will be discussed. Results are applied to the setting of noninferiority comparisons in active controlled trials where the use of a placebo is unethical.

Exploration of the validity of weak magnets as a suitable placebo in trials of magnetic therapy.

PubMed

Greaves, C J; Harlow, T N

2008-06-01

To investigate whether 50 mT magnetic bracelets would be suitable as a placebo control condition for studying the pain relieving effects of higher strength magnetic bracelets in arthritis. Randomised controlled comparison between groups given either a weak 50 mT or a higher strength 180 mT magnetic bracelets to test. Four arthritis support groups in Devon, UK. One hundred sixteen people with osteoarthritis and rheumatoid arthritis. Beliefs about group allocation and expectation of benefit. There was no significant difference between groups in beliefs about allocation to the 'active magnet' group. Participants were however more likely to have an expectation of benefit (pain relief) with the higher strength magnetic bracelets. Asking about perceived group allocation is not sufficient to rule out placebo effects in trials of magnetic bracelets which use weak magnets as a control condition. There are differences in expectation of benefit between different magnet strengths.

Dissecting polyclonal vaccine-induced humoral immunity against HIV using Systems Serology

PubMed Central

Chung, Amy W.; Kumar, Manu P.; Arnold, Kelly B.; Yu, Wen Han; Schoen, Matthew K.; Dunphy, Laura J.; Suscovich, Todd J.; Frahm, Nicole; Linde, Caitlyn; Mahan, Alison E.; Hoffner, Michelle; Streeck, Hendrik; Ackerman, Margaret E.; McElrath, M. Juliana; Schuitemaker, Hanneke; Pau, Maria G.; Baden, Lindsey R.; Kim, Jerome H.; Michael, Nelson L.; Barouch, Dan H.; Lauffenburger, Douglas A.; Alter, Galit

2017-01-01

While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc-functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine-trials. Each vaccine regimen induced a unique humoral “Fc-fingerprint”. Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive. PMID:26544943

Relearning of Activities of Daily Living: A Comparison of the Effectiveness of Three Learning Methods in Patients with Dementia of the Alzheimer Type.

PubMed

Bourgeois, J; Laye, M; Lemaire, J; Leone, E; Deudon, A; Darmon, N; Giaume, C; Lafont, V; Brinck-Jensen, S; Dechamps, A; König, A; Robert, P

2016-01-01

This study examined the effectiveness of three different learning methods: trial and error learning (TE), errorless learning (EL) and learning by modeling with spaced retrieval (MR) on the relearning process of IADL in mild-to-moderately severe Alzheimer's Dementia (AD) patients (n=52), using a 6-weeks randomized controlled trial design. The participants had to relearn three IADLs. Repeated-measure analyses during pre-intervention, post-intervention and 1-month delayed sessions were performed. All three learning methods were found to have similar efficiency. However, the intervention produced greater improvements in the actual performance of the IADL tasks than on their explicit knowledge. This study confirms that the relearning of IADL is possible with AD patients through individualized interventions, and that the improvements can be maintained even after the intervention.

Treatment of periodontal disease for glycaemic control in people with diabetes mellitus.

PubMed

Simpson, Terry C; Weldon, Jo C; Worthington, Helen V; Needleman, Ian; Wild, Sarah H; Moles, David R; Stevenson, Brian; Furness, Susan; Iheozor-Ejiofor, Zipporah

2015-11-06

Glycaemic control is a key issue in the care of people with diabetes mellitus (DM). Periodontal disease is the inflammation and destruction of the underlying supporting tissues of the teeth. Some studies have suggested a bidirectional relationship between glycaemic control and periodontal disease. This review updates the previous version published in 2010. The objective is to investigate the effect of periodontal therapy on glycaemic control in people with diabetes mellitus. We searched the following electronic databases: the Cochrane Oral Health Group Trials Register (to 31 December 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2014, Issue 11), MEDLINE via OVID (1946 to 31 December 2014), EMBASE via OVID (1980 to 31 December 2014), LILACS via BIREME (1982 to 31 December 2014), and CINAHL via EBSCO (1937 to 31 December 2014). ZETOC (1993 to 31 December 2014) and Web of Knowledge (1990 to 31 December 2014) were searched for conference proceedings. Additionally, two periodontology journals were handsearched for completeness, Annals of Periodontology (1996 to 2003) and Periodontology 2000 (1993 to 2003). We searched the US National Institutes of Health Trials Registry (http://clinicaltrials.gov) and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. We searched for randomised controlled trials (RCTs) of people with type 1 or type 2 DM (T1DM/T2DM) with a diagnosis of periodontitis. Interventions included periodontal treatments such as mechanical debridement, surgical treatment and antimicrobial therapy. Two broad comparisons were proposed:1. periodontal therapy versus no active intervention/usual care;2. periodontal therapy versus alternative periodontal therapy. For this review update, at least two review authors independently examined the titles and abstracts retrieved by the search, selected the included trials, extracted data from included trials and assessed included trials for risk of bias.Our primary outcome was blood glucose levels measured as glycated (glycosylated) haemoglobin assay (HbA1c).Our secondary outcomes included adverse effects, periodontal indices (bleeding on probing (BOP), clinical attachment level (CAL), gingival index (GI), plaque index (PI) and probing pocket depth (PPD)), cost implications and diabetic complications. We included 35 studies (including seven from the previous version of the review), which included 2565 participants in total. All studies used a parallel RCT design, and 33 studies (94%) only targeted T2DM patients. There was variation between studies with regards to included age groups (ages 18 to 80), duration of follow-up (3 to 12 months), use of antidiabetic therapy, and included participants' baseline HbA1c levels (from 5.5% to 13.1%).We assessed 29 studies (83%) as being at high risk of bias, two studies (6%) as being at low risk of bias, and four studies (11%) as unclear. Thirty-four of the studies provided data suitable for analysis under one or both of the two comparisons.Comparison 1: low quality evidence from 14 studies (1499 participants) comparing periodontal therapy with no active intervention/usual care demonstrated that mean HbA1c was 0.29% lower (95% confidence interval (CI) 0.48% to 0.10% lower) 3 to 4 months post-treatment, and 0.02% lower after 6 months (five studies, 826 participants; 95% CI 0.20% lower to 0.16% higher).Comparison 2: 21 studies (920 participants) compared different periodontal therapies with each other. There was only very low quality evidence for the multiple head-to-head comparisons, the majority of which were unsuitable to be pooled, and provided no clear evidence of a benefit for one periodontal intervention over another. We were able to pool the specific comparison between scaling and root planing (SRP) plus antimicrobial versus SRP and there was no consistent evidence that the addition of antimicrobials to SRP was of any benefit to delivering SRP alone (mean HbA1c 0.00% lower: 12 studies, 450 participants; 95% CI 0.22% lower to 0.22% higher) at 3-4 months post-treatment, or after 6 months (mean HbA1c 0.04% lower: five studies, 206 patients; 95% CI 0.41% lower to 0.32% higher).Less than half of the studies measured adverse effects. The evidence was insufficient to conclude whether any of the treatments were associated with harm. No other patient-reported outcomes (e.g. quality of life) were measured by the included studies, and neither were cost implications or diabetic complications.Studies showed varying degrees of success with regards to achieving periodontal health, with some showing high levels of residual inflammation following treatment. Statistically significant improvements were shown for all periodontal indices (BOP, CAL, GI, PI and PPD) at 3-4 and 6 months in comparison 1; however, this was less clear for individual comparisons within the broad category of comparison 2. There is low quality evidence that the treatment of periodontal disease by SRP does improve glycaemic control in people with diabetes, with a mean percentage reduction in HbA1c of 0.29% at 3-4 months; however, there is insufficient evidence to demonstrate that this is maintained after 4 months.There was no evidence to support that one periodontal therapy was more effective than another in improving glycaemic control in people with diabetes mellitus.In clinical practice, ongoing professional periodontal treatment will be required to maintain clinical improvements beyond 6 months. Further research is required to determine whether adjunctive drug therapies should be used with periodontal treatment. Future RCTs should evaluate this, provide longer follow-up periods, and consider the inclusion of a third 'no treatment' control arm.Larger, well conducted and clearly reported studies are needed in order to understand the potential of periodontal treatment to improve glycaemic control among people with diabetes mellitus. In addition, it will be important in future studies that the intervention is effective in reducing periodontal inflammation and maintaining it at lowered levels throughout the period of observation.

InterGeo II: International Geographical Achievement Test. Field Trials Report and Test (Secondary Schools, Grade 8).

ERIC Educational Resources Information Center

Niemz, Gunter; Stoltman, Joseph P.

InterGeo II, a project of the Commission on Geographical Education (CGE) of the International Geographical Union (IGU), has developed a broadly based, field-trialed testing instrument for making cross-national comparisons of achievement in geography. Field trials of InterGeo II were held in 23 countries. Data were analyzed for national achievement…

Therapeutic Plasma Transfusion in Bleeding Patients: A Systematic Review.

PubMed

Levy, Jerrold H; Grottke, Oliver; Fries, Dietmar; Kozek-Langenecker, Sibylle

2017-04-01

Plasma products, including fresh frozen plasma, are administered extensively in a variety of settings from massive transfusion to vitamin K antagonist reversal. Despite the widespread use of plasma as a hemostatic agent in bleeding patients, its effect in comparison with other available choices of hemostatic therapies is unclear. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed Central, and databases of ongoing trials for randomized controlled trials that assessed the efficacy and/or safety of therapeutic plasma as an intervention to treat bleeding patients compared with other interventions or placebo. Of 1243 unique publications retrieved in our initial search, no randomized controlled trials were identified. Four nonrandomized studies described the effect of therapeutic plasma in bleeding patients; however, data gathered from these studies did not allow for comparison with other therapeutic interventions primarily as a result of the low number of patients and the use of different (or lack of) comparators. We identified two ongoing trials investigating the efficacy and safety of therapeutic plasma, respectively; however, no data have been released as yet. Although plasma is used extensively in the treatment of bleeding patients, evidence from randomized controlled trials comparing its effect with those of other therapeutic interventions is currently lacking.

Evaluating the Specificity of Cognitive Control Deficits in Schizophrenia Using Antisaccades, Functional Magnetic Resonance Imaging, and Healthy Individuals With Poor Cognitive Control.

PubMed

Rodrigue, Amanda L; Schaeffer, David J; Pierce, Jordan E; Clementz, Brett A; McDowell, Jennifer E

2018-01-01

Cognitive control impairments in schizophrenia (SZ) can be evaluated using antisaccade tasks and functional magnetic resonance imaging (fMRI). Studies, however, often compare people with SZ to high performing healthy people, making it unclear if antisaccade-related disruptions are specific to the disease or due to generalized deficits in cognitive control. We included two healthy comparison groups in addition to people with SZ: healthy people with high cognitive control (HCC), who represent a more typical comparison group, and healthy people with low cognitive control (LCC), who perform similarly on antisaccade measures as people with SZ. Using two healthy comparison groups may help determine which antisaccade-related deficits are specific to SZ (distinguish SZ from LCC and HCC groups) and which are due to poor cognitive control (distinguish the LCC and SZ groups from the HCC group). People with SZ and healthy people with HCC or LCC performed an antisaccade task during fMRI acquisition. LCC and SZ groups showed under-activation of saccade circuitry. SZ-specific disruptions were observed in the left superior temporal gyrus and insula during error trials (suppression of activation in the SZ group compared to the LCC and HCC group). Differences related to antisaccade errors may distinguish people with SZ from healthy people with LCC.

Issues in the design of multisite clinical trials of psychotherapy: VA Cooperative Study No. 494 as an example.

PubMed

Schnurr, Paula P; Friedman, Matthew J; Engel, Charles C; Foa, Edna B; Shea, M Tracie; Resick, Patricia M; James, Kenneth E; Chow, Bruce K

2005-12-01

This article describes issues in the design of an ongoing multisite randomized clinical trial of psychotherapy for treating posttraumatic stress disorder (PTSD) in female veterans and active duty personnel. Research aimed at testing treatments for PTSD in women who have served in the military is especially important due to the high prevalence of PTSD in this population. VA Cooperative Study 494 was designed to enroll 384 participants across 12 sites. Participants are randomly assigned to receive 10 weekly sessions of individual psychotherapy: Prolonged Exposure, a specific cognitive-behavioral therapy protocol for PTSD, or present-centered therapy, a comparison treatment that addresses current interpersonal problems but avoids a trauma focus. PTSD is the primary outcome. Additional outcomes are comorbid problems such as depression and anxiety; psychosocial function and quality of life; physical health status; satisfaction with treatment; and service utilization. Follow-up assessments are conducted at the end of treatment and then 3 and 6 months after treatment. Both treatments are delivered according to a manual. Videotapes of therapy sessions are viewed by experts who provide feedback to therapists throughout the trial to ensure adherence to the treatment manual. Discussion includes issues encountered in multisite psychotherapy trials along with the rationale for our decisions about how we addressed these issues in CSP #494.

Study protocol: can a school gardening intervention improve children's diets?

PubMed

Christian, Meaghan S; El Evans, Charlotte; Conner, Mark; Ransley, Joan K; Cade, Janet E

2012-04-26

The current academic literature suggests there is a potential for using gardening as a tool to improve children's fruit and vegetable intake. This study is two parallel randomised controlled trials (RCT) devised to evaluate the school gardening programme of the Royal Horticultural Society (RHS) Campaign for School Gardening, to determine if it has an effect on children's fruit and vegetable intake. Trial One will consist of 26 schools; these schools will be randomised into two groups, one to receive the intensive intervention as "Partner Schools" and the other to receive the less intensive intervention as "Associate Schools". Trial Two will consist of 32 schools; these schools will be randomised into either the less intensive intervention "Associate Schools" or a comparison group with delayed intervention. Baseline data collection will be collected using a 24-hour food diary (CADET) to collect data on dietary intake and a questionnaire exploring children's knowledge and attitudes towards fruit and vegetables. A process measures questionnaire will be used to assess each school's gardening activities. The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children's fruit and vegetable intake. The evaluation will provide valuable information for designing future research in primary school children's diets and school based interventions. ISRCTN11396528.

A randomized, controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil as a treatment of agitated behaviour in dementia.

PubMed

O'Connor, Daniel W; Eppingstall, Barbara; Taffe, John; van der Ploeg, Eva S

2013-11-13

Lavender essential oil shows evidence of sedative properties in neurophysiological and animal studies but clinical trials of its effectiveness as a treatment of agitation in people with dementia have shown mixed results. Study methods have varied widely, however, making comparisons hazardous. To help remedy previous methodological shortcomings, we delivered high grade lavender oil in specified amounts to nursing home residents whose agitated behaviours were recorded objectively. 64 nursing home residents with frequent physically agitated behaviours were entered into a randomized, single-blind cross-over trial of dermally-applied, neurophysiologically active, high purity 30% lavender oil versus an inactive control oil. A blinded observer counted the presence or absence of target behaviours and rated participants' predominant affect during each minute for 30 minutes prior to exposure and for 60 minutes afterwards. Lavender oil did not prove superior to the control oil in reducing the frequency of physically agitated behaviours or in improving participants' affect. Studies of essential oils are constrained by their variable formulations and uncertain pharmacokinetics and so optimal dosing and delivery regimens remain speculative. Notwithstanding this, topically delivered, high strength, pure lavender oil had no discernible effect on affect and behaviour in a well-defined clinical sample. Australian and New Zealand Clinical Trials Registry (ACTRN 12609000569202).

Changes in the Healthy Beverage Index in Response to an Intervention Targeting a Reduction in Sugar-Sweetened Beverage Consumption as Compared to an Intervention Targeting Improvements in Physical Activity: Results from the Talking Health Trial.

PubMed

Hedrick, Valisa E; Davy, Brenda M; Myers, Emily A; You, Wen; Zoellner, Jamie M

2015-12-04

The recently developed Healthy Beverage Index (HBI) was designed to evaluate overall beverage intake quality (including total fluid consumption and beverage calories), yet no known intervention studies have assessed longitudinal changes to the HBI. The objective of this investigation was to assess changes in HBI scores in response to a sugar-sweetened beverage (SSB) reduction trial as compared to a physical activity comparison group. Participants were enrolled into a six-month, community-based, controlled behavioral trial and randomized into either a SSB reduction group (SIPsmartER) or a physical activity group (MoveMore). Correlations and multilevel mixed-effects linear regression with intention-to-treat analyses are presented. Total HBI score significantly increased for SIPsmartER (n = 149) (mean increase = 7.5 points (5.4, 9.7), p ≤ 0.001) and MoveMore (n = 143) (mean increase = 3.4 points (1.6, 5.2), p ≤ 0.001) participants, with a significant between group effect (p ≤ 0.05), over the six-month intervention. Other significant changes in HBI components for SIPsmartER included increased SSB and total beverage calorie scores, and decreased low-fat milk and diet soda scores. Changes in total HBI scores were significantly correlated with changes in total Healthy Eating Index-2010 scores (r = 0.15, p ≤ 0.01). Our findings suggest that individual HBI component scores, beyond the SSB component, are influenced by intervention strategies that primarily focus on SSB reduction.

Hemodynamic responses in amygdala and hippocampus distinguish between aversive and neutral cues during Pavlovian fear conditioning in behaving rats

PubMed Central

McHugh, Stephen B; Marques-Smith, Andre; Li, Jennifer; Rawlins, J N P; Lowry, John; Conway, Michael; Gilmour, Gary; Tricklebank, Mark; Bannerman, David M

2013-01-01

Lesion and electrophysiological studies in rodents have identified the amygdala and hippocampus (HPC) as key structures for Pavlovian fear conditioning, but human functional neuroimaging studies have not consistently found activation of these structures. This could be because hemodynamic responses cannot detect the sparse neuronal activity proposed to underlie conditioned fear. Alternatively, differences in experimental design or fear levels could account for the discrepant findings between rodents and humans. To help distinguish between these alternatives, we used tissue oxygen amperometry to record hemodynamic responses from the basolateral amygdala (BLA), dorsal HPC (dHPC) and ventral HPC (vHPC) in freely-moving rats during the acquisition and extinction of conditioned fear. To enable specific comparison with human studies we used a discriminative paradigm, with one auditory cue [conditioned stimulus (CS)+] that was always followed by footshock, and another auditory cue (CS−) that was never followed by footshock. BLA tissue oxygen signals were significantly higher during CS+ than CS− trials during training and early extinction. In contrast, they were lower during CS+ than CS− trials by the end of extinction. dHPC and vHPC tissue oxygen signals were significantly lower during CS+ than CS− trials throughout extinction. Thus, hemodynamic signals in the amygdala and HPC can detect the different patterns of neuronal activity evoked by threatening vs. neutral stimuli during fear conditioning. Discrepant neuroimaging findings may be due to differences in experimental design and/or fear levels evoked in participants. Our methodology offers a way to improve translation between rodent models and human neuroimaging. PMID:23173719

Beta oscillatory responses in healthy subjects and subjects with mild cognitive impairment☆

PubMed Central

Güntekin, Bahar; Emek-Savaş, Derya Durusu; Kurt, Pınar; Yener, Görsev Gülmen; Başar, Erol

2013-01-01

The aim of the present study was to investigate the role of beta oscillatory responses upon cognitive load in healthy subjects and in subjects with mild cognitive impairment (MCI). The role of beta oscillations upon cognitive stimulation is least studied in comparison to other frequency bands. The study included 17 consecutive patients with MCI (mean age = 70.8 ± 5.6 years) according to Petersen's criteria, and 17 age- and education-matched normal elderly controls (mean age = 68.5 ± 5.5 years). The experiments used a visual oddball paradigm. EEG was recorded at 30 cortical locations. EEG-evoked power, inter-trial phase synchronization, and event-related beta responses filtered in 15–20 Hz were obtained in response to target and non-target stimuli for both groups of subjects. In healthy subjects, EEG-evoked beta power, inter-trial phase synchronization of beta responses and event-related filtered beta responses were significantly higher in responses to target than non-target stimuli (p < 0.05). In MCI patients, there were no differences in evoked beta power between target and non-target stimuli. Furthermore, upon presentation of visual oddball paradigm, occipital electrodes depict higher beta response in comparison to other electrode sites. The increased beta response upon presentation of target stimuli in healthy subjects implies that beta oscillations could shift the system to an attention state, and had important function in cognitive activity. This may, in future, open the way to consider beta activity as an important operator in brain cognitive processes. PMID:24179847

Anti-inflammatory activity of Shirishavaleha: An Ayurvedic compound formulation.

PubMed

Yadav, Shyamlal Singh; Galib; Ravishankar, B; Prajapati, P K; Ashok, B K; Varun, B

2010-10-01

The purpose of the present study was to evaluate the anti-inflammatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth.), viz. the bark (Twak) and the heartwood (Sara). The activity was screened in the carrageenan-induced rat paw edema model in albino rats. The raw materials were collected and authenticated in the university and the trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for 5 days. Phenylbutazone was used as the standard anti-inflammatory drug for comparison. Between the two different test samples studied, the formulation made from heartwood showed a weak anti-inflammatory activity in this model while that made from the bark produced a considerable suppression of edema after 6 h. It appears that the bark sample would be preferable for clinical use.

Evidence of MAOA genotype involvement in spatial ability in males.

PubMed

Mueller, Sven C; Cornwell, Brian R; Grillon, Christian; Macintyre, Jessica; Gorodetsky, Elena; Goldman, David; Pine, Daniel S; Ernst, Monique

2014-07-01

Although the monoamine oxidase-A (MAOA) gene has been linked to spatial learning and memory in animal models, convincing evidence in humans is lacking. Performance on an ecologically-valid, virtual computer-based equivalent of the Morris Water Maze task was compared between 28 healthy males with the low MAOA transcriptional activity and 41 healthy age- and IQ-matched males with the high MAOA transcriptional activity. The results revealed consistently better performance (reduced heading error, shorter path length, and reduced failed trials) for the high MAOA activity individuals relative to the low activity individuals. By comparison, groups did not differ on pre-task variables or strategic measures such as first-move latency. The results provide novel evidence of MAOA gene involvement in human spatial navigation using a virtual analogue of the Morris Water Maze task. Copyright © 2014 Elsevier B.V. All rights reserved.

Sexual steroids in serum and prostatic tissue of human non-cancerous prostate (STERPROSER trial).

PubMed

Neuzillet, Yann; Raynaud, Jean-Pierre; Radulescu, Camélia; Fiet, Jean; Giton, Franck; Dreyfus, Jean-François; Ghoneim, Tarek P; Lebret, Thierry; Botto, Henry

2017-11-01

The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume. Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI). Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates. STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase. © 2017 Wiley Periodicals, Inc.

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

PubMed

Sandborn, William J; Su, Chinyu; Sands, Bruce E; D'Haens, Geert R; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul; Panés, Julian

2017-05-04

Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks. In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (P<0.001 for both comparisons with placebo). In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels. In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.).

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

PubMed Central

Wiljer, David; Cafazzo, Joseph A

2016-01-01

Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η2=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η2=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η2=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r2=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). Conclusions mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients. PMID:27613084

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

PubMed

Pham, Quynh; Wiljer, David; Cafazzo, Joseph A

2016-09-09

Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η(2)=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η(2)=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η(2)=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r(2)=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients.

Case Study: Ticagrelor in PLATO and Prasugrel in TRITON-TIMI 38 and TRILOGY-ACS Trials in Patients With Acute Coronary Syndromes

PubMed Central

Husted, Steen; Boersma, Eric

2016-01-01

Cross-trial comparisons are typically inappropriate as there are often numerous differences in study designs, populations, end points, and loading doses of the study drugs. These differences are clearly reflected in the most recent updates to the European Society of Cardiology (ESC) non-ST elevation acute coronary syndrome (NSTE-ACS) and ST elevation myocardial infarction (STEMI) guidelines, which include recommendations for the use of the antiplatelet agents ticagrelor, prasugrel, and clopidogrel, based in part on results from the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel–Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38, TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY-ACS) and PLATelet inhibition and patient Outcomes (PLATO) trials. Here, we describe each of these trials in detail and explain the differences between them that make direct comparisons difficult. In conclusion, this information, along with the current guidelines and recommendations, will assist clinicians in deciding the most appropriate treatment pathway for their patients with NSTE-ACS and STEMI. PMID:25830867

Echinacea for preventing and treating the common cold

PubMed Central

Karsch-Völk, Marlies; Barrett, Bruce; Kiefer, David; Bauer, Rudolf; Ardjomand-Woelkart, Karin; Linde, Klaus

2014-01-01

Background Echinacea plant preparations (family Asteraceae) are widely used in Europe and North America for common colds. Most consumers and physicians are not aware that products available under the term Echinacea differ appreciably in their composition, mainly due to the use of variable plant material, extraction methods and the addition of other components. Objectives To assess whether there is evidence that Echinacea preparations are effective and safe compared to placebo in the prevention and treatment of the common cold. Search methods We searched CENTRAL 2013, Issue 5, MEDLINE (1946 to May week 5, 2013), EMBASE (1991 to June 2013), CINAHL (1981 to June 2013), AMED (1985 to February 2012), LILACS (1981 to June 2013), Web of Science (1955 to June 2013), CAMBASE (no time limits), the Centre for Complementary Medicine Research (1988 to September 2007), WHO ICTRP and clinicaltrials.gov (last searched 5 June 2013), screened references and asked experts in the field about published and unpublished studies. Selection criteria Randomized controlled trials (RCTs) comparing mono-preparations of Echinacea with placebo. Data collection and analysis At least two review authors independently assessed eligibility and trial quality and extracted data. The primary efficacy outcome was the number of individuals with at least one cold in prevention trials and the duration of colds in treatment trials. For all included trials the primary safety and acceptability outcome was the number of participants dropping out due to adverse events. We assessed trial quality using the Cochrane ’Risk of bias’ tool. Main results Twenty-four double-blind trials with 4631 participants including a total of 33 comparisons of Echinacea preparations and placebo met the inclusion criteria. A variety of different Echinacea preparations based on different species and parts of plant were used. Evidence from seven trials was available for preparations based on the aerial parts of Echinacea purpurea. Ten trials were considered to have a low risk of bias, six to have an unclear risk of bias and eight to have a high risk of bias. Ten trials with 13 comparisons investigated prevention and 15 trials with 20 comparisons investigated treatment of colds (one trial addressed both prevention and treatment). Due to the strong clinical heterogeneity of the studies we refrained from pooling for the main analysis. None of the 12 prevention comparisons reporting the number of patients with at least one cold episode found a statistically significant difference. However a post hoc pooling of their results, suggests a relative risk reduction of 10% to 20%. Of the seven treatment trials reporting data on the duration of colds, only one showed a significant effect of Echinacea over placebo. The number of patients dropping out or reporting adverse effects did not differ significantly between treatment and control groups in prevention and treatment trials. However, in prevention trials there was a trend towards a larger number of patients dropping out due to adverse events in the treatment groups. Authors’ conclusions Echinacea products have not here been shown to provide benefits for treating colds, although, it is possible there is a weak benefit from some Echinacea products: the results of individual prophylaxis trials consistently show positive (if non-significant) trends, although potential effects are of questionable clinical relevance. PMID:24554461

Over the counter (OTC) artificial tear drops for dry eye syndrome.

PubMed

Pucker, Andrew D; Ng, Sueko M; Nichols, Jason J

2016-02-23

Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi-randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears. To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches. This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy. We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text. We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations.

Oxytocin reduces amygdala activity, increases social interactions and reduces anxiety-like behavior irrespective of NMDAR antagonism

PubMed Central

Sobota, Rosanna; Mihara, Takuma; Forrest, Alexandra; Featherstone, Robert E.; Siegel, Steven J.

2015-01-01

Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala leading to increased fear and social anxiety. Several studies have demonstrated the pro-social effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of sub-chronic oxytocin on electroencephalographic (EEG) activity in amygdala of mice during performance of the three chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine, but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, while oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate pro-social and social anxiety pathways may mediate social preference. PMID:26214213

The Dopaminergic Midbrain Encodes the Expected Certainty about Desired Outcomes.

PubMed

Schwartenbeck, Philipp; FitzGerald, Thomas H B; Mathys, Christoph; Dolan, Ray; Friston, Karl

2015-10-01

Dopamine plays a key role in learning; however, its exact function in decision making and choice remains unclear. Recently, we proposed a generic model based on active (Bayesian) inference wherein dopamine encodes the precision of beliefs about optimal policies. Put simply, dopamine discharges reflect the confidence that a chosen policy will lead to desired outcomes. We designed a novel task to test this hypothesis, where subjects played a "limited offer" game in a functional magnetic resonance imaging experiment. Subjects had to decide how long to wait for a high offer before accepting a low offer, with the risk of losing everything if they waited too long. Bayesian model comparison showed that behavior strongly supported active inference, based on surprise minimization, over classical utility maximization schemes. Furthermore, midbrain activity, encompassing dopamine projection neurons, was accurately predicted by trial-by-trial variations in model-based estimates of precision. Our findings demonstrate that human subjects infer both optimal policies and the precision of those inferences, and thus support the notion that humans perform hierarchical probabilistic Bayesian inference. In other words, subjects have to infer both what they should do as well as how confident they are in their choices, where confidence may be encoded by dopaminergic firing. © The Author 2014. Published by Oxford University Press.

The Dopaminergic Midbrain Encodes the Expected Certainty about Desired Outcomes

PubMed Central

Schwartenbeck, Philipp; FitzGerald, Thomas H. B.; Mathys, Christoph; Dolan, Ray; Friston, Karl

2015-01-01

Dopamine plays a key role in learning; however, its exact function in decision making and choice remains unclear. Recently, we proposed a generic model based on active (Bayesian) inference wherein dopamine encodes the precision of beliefs about optimal policies. Put simply, dopamine discharges reflect the confidence that a chosen policy will lead to desired outcomes. We designed a novel task to test this hypothesis, where subjects played a “limited offer” game in a functional magnetic resonance imaging experiment. Subjects had to decide how long to wait for a high offer before accepting a low offer, with the risk of losing everything if they waited too long. Bayesian model comparison showed that behavior strongly supported active inference, based on surprise minimization, over classical utility maximization schemes. Furthermore, midbrain activity, encompassing dopamine projection neurons, was accurately predicted by trial-by-trial variations in model-based estimates of precision. Our findings demonstrate that human subjects infer both optimal policies and the precision of those inferences, and thus support the notion that humans perform hierarchical probabilistic Bayesian inference. In other words, subjects have to infer both what they should do as well as how confident they are in their choices, where confidence may be encoded by dopaminergic firing. PMID:25056572

75 FR 12769 - National Center for Complementary and Alternative Medicine Announcement of Workshop on Control...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

... Complementary and Alternative Medicine Announcement of Workshop on Control/Comparison Groups for Trials of Non... the strengths and weaknesses of the various control/comparison groups used in studies of NPI and the most appropriate use of these control/ comparison groups. This workshop will be divided into six...

Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD): a systematic review of randomized clinical trials.

PubMed

De Crescenzo, Franco; Perelli, Federica; Armando, Marco; Vicari, Stefano

2014-01-01

The treatment of postpartum depression with selective serotonin reuptake inhibitors (SSRIs) has been claimed to be both efficacious and well tolerated, but no recent systematic reviews have been conducted. A qualitative systematic review of randomized clinical trials on women with postpartum depression comparing SSRIs to placebo and/or other treatments was performed. A comprehensive literature search of online databases, the bibliographies of published articles and grey literature were conducted. Data on efficacy, acceptability and tolerability were extracted and the quality of the trials was assessed. Six randomised clinical trials, comprising 595 patients, met quality criteria for inclusion in the analysis. Cognitive-behavioural intervention, psychosocial community-based intervention, psychodynamic therapy, cognitive behavioural therapy, a second-generation tricyclic antidepressant and placebo were used as comparisons. All studies demonstrated higher response and remission rates among those treated with SSRIs and greater mean changes on depression scales, although findings were not always statistically significant. Dropout rates were high in three of the trials but similar among treatment and comparison groups. In general, SSRIs were well tolerated and trial quality was good. There are few trials, patients included in the trials were not representative of all patients with postpartum depression, dropout rates in three trials were high, and long-term efficacy and tolerability were assessed in only two trials. SSRIs appear to be efficacious and well tolerated in the treatment of postpartum depression, but the available evidence fails to demonstrate a clear superiority over other treatments. © 2013 Elsevier B.V. All rights reserved.

Physiotherapy for Parkinson's disease: a comparison of techniques.

PubMed

Tomlinson, Claire L; Herd, Clare P; Clarke, Carl E; Meek, Charmaine; Patel, Smitaa; Stowe, Rebecca; Deane, Katherine H O; Shah, Laila; Sackley, Catherine M; Wheatley, Keith; Ives, Natalie

2014-06-17

Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. The role of physiotherapy is to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety and wellbeing, thereby enhancing quality of life. Trials have shown that physiotherapy has short-term benefits in PD. However, which physiotherapy intervention is most effective remains unclear. To assess the effectiveness of one physiotherapy intervention compared with a second approach in patients with PD. Relevant trials were identified by electronic searches of numerous literature databases (for example MEDLINE, EMBASE) and trial registers, plus handsearching of major journals, abstract books, conference proceedings and reference lists of retrieved publications. The literature search included trials published up to the end of January 2012. Randomised controlled trials of one physiotherapy intervention versus another physiotherapy intervention in patients with PD. Data were abstracted independently from each paper by two authors. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance and martial arts. A total of 43 trials were identified with 1673 participants. All trials used small patient numbers (average trial size of 39 participants); the methods of randomisation and concealment of allocation were poor or not stated in most trials. Blinded assessors were used in just over half of the trials and only 10 stated that they used intention-to-treat analysis.A wide variety of validated and customised outcome measures were used to assess the effectiveness of physiotherapy interventions. The most frequently reported physiotherapy outcomes were gait speed and timed up and go, in 19 and 15 trials respectively. Only five of the 43 trials reported data on falls (12%). The motor subscales of the Unified Parkinson's Disease Rating Scale and Parkinson's Disease Questionnaire-39 were the most commonly reported clinician-rated disability and patient-rated quality of life outcome measures, used in 22 and 13 trials respectively. The content and delivery of the physiotherapy interventions varied widely in the trials included within this review, so no quantitative meta-analysis could be performed. Considering the small number of participants examined, the methodological flaws in many of the studies, the possibility of publication bias, and the variety of interventions, formal comparison of the different physiotherapy techniques could not be performed. There is insufficient evidence to support or refute the effectiveness of one physiotherapy intervention over another in PD.This review shows that a wide range of physiotherapy interventions to treat PD have been tested . There is a need for more specific trials with improved treatment strategies to underpin the most appropriate choice of physiotherapy intervention and the outcomes measured.

Multisensory Stimulation as an Intervention Strategy for Elderly Patients With Severe Dementia: A Pilot Randomized Controlled Trial.

PubMed

Sánchez, Alba; Marante-Moar, M Pilar; Sarabia, Carmen; de Labra, Carmen; Lorenzo, Trinidad; Maseda, Ana; Millán-Calenti, José Carlos

2016-06-01

The objective of this study was to compare the effect of multisensory stimulation environment (MSSE) and one-to-one activity sessions in the symptomatology of elderly individuals with severe dementia. Thirty-two participants were randomly assigned to the following 3 groups: MSSE, activity, and control group. The MSSE and activity groups participated in two 30-minute weekly sessions over 16 weeks. Pre-, mid-, and posttrial; 8-week follow-up behavior; mood; cognitive status; and dementia severity were registered. Patients in the MSSE group demonstrated a significant improvement in the Neuropsychiatric Inventory and Bedford Alzheimer Nursing Severity Scale scores compared with the activity group. Both MSSE and activity groups showed an improvement during the intervention in the Cohen-Mansfield Agitation Inventory aggressive behavior factor and total score, with no significant differences between groups. The MSSE may have better effects on neuropsychiatric symptoms and dementia severity in comparison with one-to-one activity sessions in patients with severe dementia. © The Author(s) 2015.

Assessing the Effects of Interpersonal and Intrapersonal Behavior Change Strategies on Physical Activity in Older Adults: a Factorial Experiment.

PubMed

McMahon, Siobhan K; Lewis, Beth; Oakes, J Michael; Wyman, Jean F; Guan, Weihua; Rothman, Alexander J

2017-06-01

Little is known about which behavior change strategies motivate older adults to increase their physical activity. The purpose of this study was to assess the relative effects of two sets of behavior change strategies to motivate increased physical activity among older adults: interpersonal and intrapersonal. Community-dwelling older adults (N = 102, mean age = 79) were randomized in a 2 × 2 factorial experiment to receive interpersonal (e.g., social support, friendly social comparison; no, yes) and /or intrapersonal (e.g., goal setting, barriers management; no, yes) behavior change strategies, combined with an evidence-based, physical activity protocol (Otago exercise program) and a physical activity monitor (Fitbit One™). Based on monitor data, participants who received interpersonal strategies, compared to those who did not, increased their average minutes of total physical activity (light, moderate, vigorous) per week, immediately (p = .006) and 6 months (p = .048) post-intervention. Similar, increases were observed on measures of functional strength and balance, immediately (p = .012) and 6 months (p = .003) post-intervention. The intrapersonal strategies did not elicit a significant increase in physical activity or functional strength and balance. Findings suggest a set of interpersonally oriented behavior change strategies combined with an evidence-based physical activity protocol can elicit modest, but statistically and clinically significant, increases in older adults' physical activity and functional strength and balance. Future research should replicate these findings and investigate the sustained quantity of physical activity elicited by these strategies and their impact on older adults' quality of life and falls. Trial Registration The ClinicalTrials.gov registration identifier is NCT02433249.

Working alliance and empathy as mediators of brief telephone counseling for cigarette smokers who are not ready to quit

PubMed Central

Klemperer, Elias M.; Hughes, John R.; Callas, Peter W.; Solomon, Laura J.

2016-01-01

Working alliance and empathy are believed to be important components of counseling, though few studies have empirically tested this. We recently conducted a randomized controlled trial in which brief motivational and reduction counseling failed to increase the number of participants who made a quit attempt (QA) in comparison to usual care (i.e., brief advice to quit). Our negative findings could have been due to non-specific factors. This secondary analysis used a subset of participants (n=347) to test a) whether, in comparison to usual care, brief telephone-based motivational or reduction counseling predicted greater working alliance or empathy, b) whether changes in these non-specific factors predicted an increased probability of a QA at a 6-month follow-up, and c) whether counseling affected the probability of a QA via working alliance or empathy (i.e., mediation). Findings were similar for both active counseling conditions (motivational and reduction) vs usual care. In comparison to usual care, active counseling predicted greater working alliance (p<.001) and empathy (p<.05). Greater working alliance predicted a greater probability of a QA (p<.001) but, surprisingly, greater empathy predicted a decreased probability of a QA (p<.05) at the 6-month follow-up. Both working alliance (p<.001) and empathy (p<.05) mediated the active counseling's effects on the probability of a QA. One explanation for our motivational and reduction interventions' failure to influence QAs in comparison to usual care is that working alliance and empathy had opposing effects on quitting. Our analyses illustrate how testing non-specific factors as mediators can help explain why a treatment failed. PMID:28165273

Working alliance and empathy as mediators of brief telephone counseling for cigarette smokers who are not ready to quit.

PubMed

Klemperer, Elias M; Hughes, John R; Callas, Peter W; Solomon, Laura J

2017-02-01

Working alliance and empathy are believed to be important components of counseling, although few studies have empirically tested this. We recently conducted a randomized controlled trial in which brief motivational and reduction counseling failed to increase the number of participants who made a quit attempt (QA) in comparison to usual care (i.e., brief advice to quit). Our negative findings could have been due to nonspecific factors. This secondary analysis used a subset of participants (n = 347) to test (a) whether, in comparison to usual care, brief telephone-based motivational or reduction counseling predicted greater working alliance or empathy; (b) whether changes in these nonspecific factors predicted an increased probability of a QA at a 6-month follow-up; and (c) whether counseling affected the probability of a QA via working alliance or empathy (i.e., mediation). Findings were similar for both active counseling conditions (motivational and reduction) versus usual care. In comparison to usual care, active counseling predicted greater working alliance (p < .001) and empathy (p < .05). Greater working alliance predicted a greater probability of a QA (p < .001) but, surprisingly, greater empathy predicted a decreased probability of a QA (p < .05) at the 6-month follow-up. Working alliance (p < .001) and empathy (p < .05) mediated the active counseling's effects on the probability of a QA. One explanation for our motivational and reduction interventions' failure to influence QAs in comparison to usual care is that working alliance and empathy had opposing effects on quitting. Our analyses illustrate how testing nonspecific factors as mediators can help explain why a treatment failed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Fear-potentiated startle processing in humans: Parallel fMRI and orbicularis EMG assessment during cue conditioning and extinction.

PubMed

Lindner, Katja; Neubert, Jörg; Pfannmöller, Jörg; Lotze, Martin; Hamm, Alfons O; Wendt, Julia

2015-12-01

Studying neural networks and behavioral indices such as potentiated startle responses during fear conditioning has a long tradition in both animal and human research. However, most of the studies in humans do not link startle potentiation and neural activity during fear acquisition and extinction. Therefore, we examined startle blink responses measured with electromyography (EMG) and brain activity measured with functional MRI simultaneously during differential conditioning. Furthermore, we combined these behavioral fear indices with brain network activity by analyzing the brain activity evoked by the startle probe stimulus presented during conditioned visual threat and safety cues as well as in the absence of visual stimulation. In line with previous research, we found a fear-induced potentiation of the startle blink responses when elicited during a conditioned threat stimulus and a rapid decline of amygdala activity after an initial differentiation of threat and safety cues in early acquisition trials. Increased activation during processing of threat cues was also found in the anterior insula, the anterior cingulate cortex (ACC), and the periaqueductal gray (PAG). More importantly, our results depict an increase of brain activity to probes presented during threatening in comparison to safety cues indicating an involvement of the anterior insula, the ACC, the thalamus, and the PAG in fear-potentiated startle processing during early extinction trials. Our study underlines that parallel assessment of fear-potentiated startle in fMRI paradigms can provide a helpful method to investigate common and distinct processing pathways in humans and animals and, thus, contributes to translational research. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect Size in Efficacy Trials of Women With Decreased Sexual Desire.

PubMed

Pyke, Robert E; Clayton, Anita H

2018-03-22

Regarding hypoactive sexual desire disorder (HSDD) in women, some reviewers judge the effect size small for medications vs placebo, but substantial for cognitive behavior therapy (CBT) or mindfulness meditation training (MMT) vs wait list. However, we lack comparisons of the effect sizes for the active intervention itself, for the control treatment, and for the differential between the two. For efficacy trials of HSDD in women, compare effect sizes for medications (testosterone/testosterone transdermal system, flibanserin, and bremelanotide) and placebo vs effect sizes for psychotherapy and wait-list control. We conducted a literature search for mean changes and SD on main measures of sexual desire and associated distress in trials of medications, CBT, or MMT. Effect size was used as it measures the magnitude of the intervention without confounding by sample size. Cohen d was used to determine effect sizes. For medications, mean (SD) effect size was 1.0 (0.34); for CBT and MMT, 1.0 (0.36); for placebo, 0.55 (0.16); and for wait list, 0.05 (0.26). Recommendations of psychotherapy over medication for treatment of HSDD are premature and not supported by data on effect sizes. Active participation in treatment conveys considerable non-specific benefits. Caregivers should attend to biological and psychosocial elements, and patient preference, to optimize response. Few clinical trials of psychotherapies were substantial in size or utilized adequate control paradigms. Medications and psychotherapies had similar, large effect sizes. Effect size of placebo was moderate. Effect size of wait-list control was very small, about one quarter that of placebo. Thus, a substantial non-specific therapeutic effect is associated with receiving placebo plus active care and evaluation. The difference in effect size between placebo and wait-list controls distorts the value of the subtraction of effect of the control paradigms to estimate intervention effectiveness. Pyke RE, Clayton AH. Effect Size in Efficacy Trials of Women With Decreased Sexual Desire. Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Exercise interventions for smoking cessation.

PubMed

Ussher, Michael H; Taylor, Adrian; Faulkner, Guy

2008-10-08

Taking regular exercise may help people give up smoking by moderating nicotine withdrawal and cravings, and by helping to manage weight gain. To determine whether exercise-based interventions alone or combined with a smoking cessation programme are more effective than a smoking cessation intervention alone. In July 2008, we searched the Cochrane Tobacco Addiction Group Specialized Register for studies including the terms 'exercise' or 'physical activity'. We also searched MEDLINE, EMBASE, PsycINFO, Dissertation Abstracts and CINAHL. We included randomized trials which compared an exercise programme alone, or an exercise programme as an adjunct to a cessation programme, with a cessation programme, recruiting smokers or recent quitters, and with a follow up of six months or more. We extracted data on study characteristics and smoking outcomes. Because of differences in studies we summarized the results narratively, making no attempt at meta-analysis. We identified 13 trials, six of which had fewer than 25 people in each treatment arm. They varied in the timing and intensity of the smoking cessation and exercise programmes. Three studies showed significantly higher abstinence rates in a physically active group versus a control group at end of treatment. One of these studies also showed a significant benefit for exercise versus control on abstinence at the three-month follow up and a benefit for exercise of borderline significance (P = 0.05) at the 12-month follow up. One study showed significantly higher abstinence rates for the exercise group versus a control group at the three-month follow up but not at the end of treatment or 12-month follow up. The other studies showed no significant effect for exercise on abstinence. Only one of the 13 trials offered evidence for exercise aiding smoking cessation at a 12-month follow up. All the other trials were too small to exclude reliably an effect of intervention, or included an exercise intervention which was insufficiently intense to achieve the desired level of exercise. Trials are needed with larger sample sizes, sufficiently intense interventions, equal contact control conditions, measures of exercise adherence and change in physical activity in both exercise and comparison groups.

Cow weights and calf production for pasture 12-C Lehmann lovegrass grazing trials, 1982 to 1993

Treesearch

Phil R. Ogden; E. Lamar Smith

2003-01-01

The purpose of the grazing trials described in this paper was to provide information to aid in the development of grazing management strategies where Lehmann lovegrass has become a dominant species. Seven pastures were utilized from 1984 to 1987 for a comparison of four yearlong stocking rates to seasonal grazing rotated through three pastures. A second trial, 1988 to...

Blinded sample size re-estimation in three-arm trials with 'gold standard' design.

PubMed

Mütze, Tobias; Friede, Tim

2017-10-15

In this article, we study blinded sample size re-estimation in the 'gold standard' design with internal pilot study for normally distributed outcomes. The 'gold standard' design is a three-arm clinical trial design that includes an active and a placebo control in addition to an experimental treatment. We focus on the absolute margin approach to hypothesis testing in three-arm trials at which the non-inferiority of the experimental treatment and the assay sensitivity are assessed by pairwise comparisons. We compare several blinded sample size re-estimation procedures in a simulation study assessing operating characteristics including power and type I error. We find that sample size re-estimation based on the popular one-sample variance estimator results in overpowered trials. Moreover, sample size re-estimation based on unbiased variance estimators such as the Xing-Ganju variance estimator results in underpowered trials, as it is expected because an overestimation of the variance and thus the sample size is in general required for the re-estimation procedure to eventually meet the target power. To overcome this problem, we propose an inflation factor for the sample size re-estimation with the Xing-Ganju variance estimator and show that this approach results in adequately powered trials. Because of favorable features of the Xing-Ganju variance estimator such as unbiasedness and a distribution independent of the group means, the inflation factor does not depend on the nuisance parameter and, therefore, can be calculated prior to a trial. Moreover, we prove that the sample size re-estimation based on the Xing-Ganju variance estimator does not bias the effect estimate. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

PubMed Central

2011-01-01

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

In Vivo Knee Contact Force Prediction Using Patient-Specific Musculoskeletal Geometry in a Segment-Based Computational Model.

PubMed

Ding, Ziyun; Nolte, Daniel; Kit Tsang, Chui; Cleather, Daniel J; Kedgley, Angela E; Bull, Anthony M J

2016-02-01

Segment-based musculoskeletal models allow the prediction of muscle, ligament, and joint forces without making assumptions regarding joint degrees-of-freedom (DOF). The dataset published for the "Grand Challenge Competition to Predict in vivo Knee Loads" provides directly measured tibiofemoral contact forces for activities of daily living (ADL). For the Sixth Grand Challenge Competition to Predict in vivo Knee Loads, blinded results for "smooth" and "bouncy" gait trials were predicted using a customized patient-specific musculoskeletal model. For an unblinded comparison, the following modifications were made to improve the predictions: further customizations, including modifications to the knee center of rotation; reductions to the maximum allowable muscle forces to represent known loss of strength in knee arthroplasty patients; and a kinematic constraint to the hip joint to address the sensitivity of the segment-based approach to motion tracking artifact. For validation, the improved model was applied to normal gait, squat, and sit-to-stand for three subjects. Comparisons of the predictions with measured contact forces showed that segment-based musculoskeletal models using patient-specific input data can estimate tibiofemoral contact forces with root mean square errors (RMSEs) of 0.48-0.65 times body weight (BW) for normal gait trials. Comparisons between measured and predicted tibiofemoral contact forces yielded an average coefficient of determination of 0.81 and RMSEs of 0.46-1.01 times BW for squatting and 0.70-0.99 times BW for sit-to-stand tasks. This is comparable to the best validations in the literature using alternative models.

Physiotherapy Rehabilitation for Osteoporotic Vertebral Fracture (PROVE): study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background Osteoporosis and vertebral fracture can have a considerable impact on an individual’s quality of life. There is increasing evidence that physiotherapy including manual techniques and exercise interventions may have an important treatment role. This pragmatic randomised controlled trial will investigate the clinical and cost-effectiveness of two different physiotherapy approaches for people with osteoporosis and vertebral fracture, in comparison to usual care. Methods/Design Six hundred people with osteoporosis and a clinically diagnosed vertebral fracture will be recruited and randomly allocated to one of three management strategies, usual care (control - A), an exercise-based physiotherapy intervention (B) or a manual therapy-based physiotherapy intervention (C). Those in the usual care arm will receive a single session of education and advice, those in the active treatment arms (B + C) will be offered seven individual physiotherapy sessions over 12 weeks. The trial is designed as a prospective, adaptive single-blinded randomised controlled trial. An interim analysis will be completed and if one intervention is clearly superior the trial will be adapted at this point to continue with just one intervention and the control. The primary outcomes are quality of life measured by the disease specific QUALLEFO 41 and the Timed Loaded Standing test measured at 1 year. Discussion There are a variety of different physiotherapy packages used to treat patients with osteoporotic vertebral fracture. At present, the indication for each different therapy is not well defined, and the effectiveness of different modalities is unknown. Trial registration Reference number ISRCTN49117867. PMID:24422876

A systematic review of evidence for the effectiveness of practitioner-based complementary and alternative therapies in the management of rheumatic diseases: rheumatoid arthritis.

PubMed

Macfarlane, Gary J; Paudyal, Priya; Doherty, Michael; Ernst, Edzard; Lewith, George; MacPherson, Hugh; Sim, Julius; Jones, Gareth T

2012-09-01

To critically review the evidence on the effectiveness of complementary therapies for patients with RA. Randomized controlled trials, published in English up to May 2011, were identified using systematic searches of bibliographic databases and searching of reference lists. Information was extracted on outcomes and statistical significance in comparison with alternative treatments and reported side effects. The methodological quality of the identified studies was determined using the Jadad scoring system. All outcomes were considered but with a focus on patient global assessment and pain reporting. Eleven eligible trials were identified covering seven therapies. Three trials that compared acupuncture with sham acupuncture reported no significant difference in pain reduction between the groups but one out of two reported an improvement in patient global assessment. Except for reduction in physician's global assessment of treatment and disease activity reported in one trial, no other comparative benefit of acupuncture was seen. There were two studies on meditation and one each on autogenic training, healing therapy, progressive muscle relaxation, static magnets and tai chi. None of these trials reported positive comparative effects on pain but some positive effects on patient global assessment were noted at individual time points in the healing therapy and magnet therapy studies. A small number of other outcomes showed comparative improvement in individual trials. There were no reports of major adverse events. The very limited evidence available indicates that for none of the practitioner-based complementary therapies considered here is there good evidence of efficacy or effectiveness in the management of RA.

Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial.

PubMed

Zhong, Linda L D; Cheng, Chung Wah; Chan, Yawen; Chan, King Hong; Lam, Ting Wa; Chen, Xiao Rui; Wong, Chi Tak; Wu, Justin C Y; Bian, Zhao Xiang

2013-11-04

Functional constipation is a common clinical complaint. Although the effectiveness of Ma Zi Ren Wan for alleviating functional constipation symptoms has been proven in a previous randomized placebo-controlled study, further evidence is needed to make clinical recommendations about Chinese herbal medicine. In particular, a comparison with conventional western medicine for functional constipation patients is needed. This is a prospective, double-blinded, double dummy, randomized, controlled trial. After a 2-week run-in period, eligible patients (Rome III) with excessive traditional Chinese medicine syndrome will randomly be assigned to the Chinese medicine arm (Ma Zi Ren Wan and western medicine placebo), western medicine arm (senna and Chinese medicine placebo) or placebo arm (Chinese medicine placebo and western medicine placebo). Patients will undergo an 8-week treatment and an 8-week follow-up. The primary outcome is the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Patients with a mean increase of CSBM ≧1/week in comparison with their baselines are defined as responders. The secondary outcomes include responder rate during follow-up, changes of colonic transit as measured with radio-opaque markers, individual and global symptom assessments, and reported adverse effects. This study is the first study to compare a Chinese Herbal Medicine (Ma Zi Ren Wan) with a laxative that is commonly used in the clinical practice of western medicine, and with a placebo. This study will complete the investigation of Ma Zi Ren Wan for functional constipation, and should, therefore, suggest recommendations for clinical practice. Furthermore, the process of first conducting a systematic review, then implementing a dose determination study followed by a placebo-control trial, and finally, comparing traditional Chinese medicine with an active conventional medicine in a controlled trial can be a reference to other researches on Chinese medicine interventions in the future. NCT01695850.

Effect of activity-based mirror therapy on lower limb motor-recovery and gait in stroke: A randomised controlled trial.

PubMed

Arya, Kamal Narayan; Pandian, Shanta; Kumar, Vikas

2017-09-26

To determine the effect of activity-based mirror therapy (MT) on motor recovery and gait in chronic poststroke hemiparetic subjects. A randomised, controlled, assessor-blinded trial. Rehabilitation institute. Thirty-six chronic poststroke (15.89 ± 9.01 months) hemiparetic subjects (age: 46.44 ± 7.89 years, 30 men and functional ambulation classification of median level 3). Activity-based MT comprised movements such as ball-rolling, rocker-board, and pedalling. The activities were provided on the less-affected side in front of the mirror while hiding the affected limb. The movement of the less-affected lower limb was projected as over the affected limb. Conventional motor therapy based on neurophysiological approaches was also provided to the experimental group. The control group received only conventional management. Brunnstrom recovery stages (BRS), Fugl-Meyer assessment lower extremity (FMA-LE), Rivermead visual gait assessment (RVGA), and 10-metre walk test (10-MWT). Postintervention, the experimental group exhibited significant and favourable changes for FMA-LE (mean difference = 3.29, 95% CI = 1.23-5.35, p = .003) and RVGA (mean difference = 5.41, 95% CI = 1.12-9.71, p = .015) in comparison to the control group. No considerable changes were observed on 10-MWT. Activity-based MT facilitates motor recovery of the lower limb as well as reduces gait deviations among chronic poststroke hemiparetic subjects.

Do brief motivational interventions reduce drinking game frequency in mandated students? An analysis of data from two randomized controlled trials.

PubMed

Fernandez, Anne C; Yurasek, Ali M; Merrill, Jennifer E; Miller, Mary Beth; Zamboanga, Byron L; Carey, Kate B; Borsari, Brian

2017-02-01

College students frequently engage in drinking games (DGs) and experience a variety of consequences as a result. It is currently unknown whether brief motivational interventions (BMIs) that provide feedback on DG participation can reduce this high risk behavior. This study examined outcome data from 2 randomized clinical trials to examine whether BMIs facilitate change in DG frequency and how these changes may occur. Mandated college students (Trial 1, N = 198, 46% female; Trial 2, N = 412; 32% female) were randomized to BMI or comparison control conditions. Hierarchical linear modeling (HLM) was used to compare the BMI and comparison groups to determine whether the BMI reduced DG participation over time. Percent change talk (PCT) during the discussion of DG during the session was examined as a predictor of change in DG frequency, and gender was examined as a moderator of treatment effects. Controlling for regular drinking frequency, participants who received a BMI did not significantly reduce their DG frequency relative to the comparison group in either sample, and the BMI was equally ineffective at reducing DG behavior for men and women. DG-related PCT during the BMI was associated with lower DG frequency at the second follow-up in both trials. In Trial 1, PCT during the BMI was associated with less steep increases in DG frequency across the course of all follow-ups. Effects of PCT on DG behavior were not moderated by gender. Findings did not support hypothesized reductions in DG participation following a BMI. Future research should explore whether targeted DG-specific interventions could reduce DG participation and the role of in-session client language in facilitating such change. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Failure Rate of Direct High-Viscosity Glass-Ionomer Versus Hybrid Resin Composite Restorations in Posterior Permanent Teeth - a Systematic Review

PubMed Central

Mickenautsch, Steffen; Yengopal, Veerasamy

2015-01-01

Purpose Traditionally, resin composite restorations are claimed by reviews of the dental literature as being superior to glass-ionomer fillings in terms of restoration failures in posterior permanent teeth. The aim of this systematic review is to answer the clinical question, whether conventional high-viscosity glass-ionomer restorations, in patients with single and/or multi-surface cavities in posterior permanent teeth, have indeed a higher failure rate than direct hybrid resin composite restorations. Methods Eight databases were searched until December 02, 2013. Trials were assessed for bias risks, in-between datasets heterogeneity and statistical sample size power. Effects sizes were computed and statistically compared. A total of 55 citations were identified through systematic literature search. From these, 46 were excluded. No trials related to high-viscosity glass-ionomers versus resin composite restorations for direct head-to-head comparison were found. Three trials related to high-viscosity glass-ionomers versus amalgam and three trials related to resin composite versus amalgam restorations could be included for adjusted indirect comparison, only. Results The available evidence suggests no difference in the failure rates between both types of restoration beyond the play of chance, is limited by lack of head-to-head comparisons and an insufficient number of trials, as well as by high bias and in-between-dataset heterogeneity risk. The current clinical evidence needs to be regarded as too poor in order to justify superiority claims regarding the failure rates of both restoration types. Sufficiently large-sized, parallel-group, randomised control trials with high internal validity are needed, in order to justify any clinically meaningful judgment to this topic. PMID:26962372

Meta-analysis: aerobic exercise for the treatment of anxiety disorders.

PubMed

Bartley, Christine A; Hay, Madeleine; Bloch, Michael H

2013-08-01

This meta-analysis investigates the efficacy of exercise as a treatment for DSM-IV diagnosed anxiety disorders. We searched PubMED and PsycINFO for randomized, controlled trials comparing the anxiolytic effects of aerobic exercise to other treatment conditions for DSM-IV defined anxiety disorders. Seven trials were included in the final analysis, totaling 407 subjects. The control conditions included non-aerobic exercise, waitlist/placebo, cognitive-behavioral therapy, psychoeducation and meditation. A fixed-effects model was used to calculate the standardized mean difference of change in anxiety rating scale scores of aerobic exercise compared to control conditions. Subgroup analyses were performed to examine the effects of (1) comparison condition; (2) whether comparison condition controlled for time spent exercising and (3) diagnostic indication. Aerobic exercise demonstrated no significant effect for the treatment of anxiety disorders (SMD=0.02 (95%CI: -0.20-0.24), z = 0.2, p = 0.85). There was significant heterogeneity between trials (χ(2) test for heterogeneity = 22.7, df = 6, p = 0.001). The reported effect size of aerobic exercise was highly influenced by the type of control condition. Trials utilizing waitlist/placebo controls and trials that did not control for exercise time reported large effects of aerobic exercise while other trials report no effect of aerobic exercise. Current evidence does not support the use of aerobic exercise as an effective treatment for anxiety disorders as compared to the control conditions. This remains true when controlling for length of exercise sessions and type of anxiety disorder. Future studies evaluating the efficacy of aerobic exercise should employ larger sample sizes and utilize comparison interventions that control for exercise time. Copyright © 2013. Published by Elsevier Inc.

Do Brief Motivational Interventions Reduce Drinking Game Frequency in Mandated Students? An analysis of data from two randomized controlled trials

PubMed Central

Fernandez, Anne C.; Yurasek, Allison M.; Merrill, Jennifer E.; Miller, Mary Beth; Zamboanga, Byron L.; Carey, Kate B.; Borsari, Brian

2016-01-01

Purpose College students frequently engage in drinking games (DG) and experience a variety of consequences as a result. It is currently unknown whether brief motivational interventions (BMI) that provide feedback on DG participation can reduce this high risk behavior. This study examined outcome data from two randomized clinical trials to examine whether BMIs facilitate change in DG frequency and how these changes may occur. Methods Mandated college students (Trial 1, N = 198, 46% female; Trial 2, N = 412; 32% female) were randomized to BMI or comparison control conditions. Hierarchical linear modeling (HLM) was used to compare the BMI and comparison groups to determine whether the BMI reduced DG participation over time. Percent change talk (PCT) during the discussion of DG during the session was examined as a predictor of change in DG frequency, and gender was examined as a moderator of treatment effects. Results Controlling for regular drinking frequency, participants who received a BMI did not significantly reduce their DG frequency relative to the comparison group in either sample, and the BMI was equally ineffective at reducing DG behavior for men and women. DG-related PCT during the BMI was associated with lower DG frequency at the second follow-up in both Trials. In Trial 1, PCT during the BMI was associated with less steep increases in DG frequency across the course of all follow-ups. Effects of PCT on DG behavior were not moderated by gender. Conclusions Findings did not support hypothesized reductions in DG participation following a BMI. Future research should explore whether targeted DG-specific interventions could reduce DG participation and the role of in-session client language in facilitating such change. PMID:27936818

A randomized controlled trial to evaluate self-determination theory for exercise adherence and weight control: rationale and intervention description

PubMed Central

Silva, Marlene N; Markland, David; Minderico, Cláudia S; Vieira, Paulo N; Castro, Margarida M; Coutinho, Sílvia R; Santos, Teresa C; Matos, Margarida G; Sardinha, Luís B; Teixeira, Pedro J

2008-01-01

Background Research on the motivational model proposed by Self-Determination Theory (SDT) provides theoretically sound insights into reasons why people adopt and maintain exercise and other health behaviors, and allows for a meaningful analysis of the motivational processes involved in behavioral self-regulation. Although obesity is notoriously difficult to reverse and its recidivism is high, adopting and maintaining a physically active lifestyle is arguably the most effective strategy to counteract it in the long-term. The purposes of this study are twofold: i) to describe a 3-year randomized controlled trial (RCT) aimed at testing a novel obesity treatment program based on SDT, and ii) to present the rationale behind SDT's utility in facilitating and explaining health behavior change, especially physical activity/exercise, during obesity treatment. Methods Study design, recruitment, inclusion criteria, measurements, and a detailed description of the intervention (general format, goals for the participants, intervention curriculum, and main SDT strategies) are presented. The intervention consists of a 1-year group behavioral program for overweight and moderately obese women, aged 25 to 50 (and pre-menopausal), recruited from the community at large through media advertisement. Participants in the intervention group meet weekly or bi-weekly with a multidisciplinary intervention team (30 2 h sessions in total), and go through a program covering most topics considered critical for successful weight control. These topics and especially their delivery were adapted to comply with SDT and Motivational Interviewing guidelines. Comparison group receive a general health education curriculum. After the program, all subjects are follow-up for a period of 2 years. Discussion Results from this RCT will contribute to a better understanding of how motivational characteristics, particularly those related to physical activity/exercise behavioral self-regulation, influence treatment success, while exploring the utility of Self-Determination Theory for promoting health behavior change in the context of obesity. Trial Registration Clinical Trials Gov. Identifier NCT00513084 PMID:18613959

The impact of an exercise intervention on C - reactive protein during pregnancy: a randomized controlled trial.

PubMed

Hawkins, Marquis; Braun, Barry; Marcus, Bess H; Stanek, Edward; Markenson, Glenn; Chasan-Taber, Lisa

2015-06-24

C-reactive protein (CRP) during pregnancy has been associated with adverse maternal outcomes such as preeclampsia and gestational diabetes mellitus. Randomized trials suggest that exercise programs may be associated with reductions in CRP in non-pregnant populations; however, such studies have not been conducted among pregnant women. The purpose of this study was to evaluate the impact of an individually-tailored motivationally-matched exercise intervention on CRP in pregnant women. The Behaviors Affecting Baby and You study was a randomized controlled trial of prenatal physical activity to prevent the development of gestational diabetes mellitus in women at increased risk. Women were randomized to either a 12-week exercise intervention (n = 84) or a comparison health and wellness intervention (n = 87). High sensitivity CRP (mg/dL) was measured using a commercial immunoassay kit. Physical activity was measured using the Pregnancy Physical Activity Questionnaire. Mixed model analyses were used to evaluate the impact of the intervention on change in CRP using an intent-to-treat approach. CRP decreased (-0.09 mg/dL, 95 % CI: -0.25, 0.07) from pre- to post-intervention in the exercise arm (p = 0.14) and increased (0.08 mg/dL, 95 % CI: -0.07, 0.24) (p = 0.64) in the health and wellness arm; however the between group difference was not statistically significant (p = 0.14). Findings did not differ according to ethnic group or pre-pregnancy body mass index. In a secondary analysis based on self-reported physical activity, women who decreased their time spent in sports/exercise experienced a mean increase in CRP (0.09 mg/dL, 95 % CI: -0.14, 0.33), whereas women who maintained or increased their sports/ exercise experienced a mean decrease in CRP (-0.08 mg/dL, 95 % CI: -0.23, 0.08) (p = 0.046). Findings from this randomized trial in an ethnically and socio-economically diverse population of pregnant women were consistent with a positive impact of the exercise intervention on CRP levels, but not of statistical significance. ClinicalTrials.gov: NCT00728377 . Registered 2 August 2008.

Assessment of second-line antiretroviral regimens for HIV therapy in Africa.

PubMed

Paton, Nicholas I; Kityo, Cissy; Hoppe, Anne; Reid, Andrew; Kambugu, Andrew; Lugemwa, Abbas; van Oosterhout, Joep J; Kiconco, Mary; Siika, Abraham; Mwebaze, Raymond; Abwola, Mary; Abongomera, George; Mweemba, Aggrey; Alima, Hillary; Atwongyeire, Dickens; Nyirenda, Rose; Boles, Justine; Thompson, Jennifer; Tumukunde, Dinah; Chidziva, Ennie; Mambule, Ivan; Arribas, Jose R; Easterbrook, Philippa J; Hakim, James; Walker, A Sarah; Mugyenyi, Peter

2014-07-17

The efficacy and toxic effects of nucleoside reverse-transcriptase inhibitors (NRTIs) are uncertain when these agents are used with a protease inhibitor in second-line therapy for human immunodeficiency virus (HIV) infection in resource-limited settings. Removing the NRTIs or replacing them with raltegravir may provide a benefit. In this open-label trial in sub-Saharan Africa, we randomly assigned 1277 adults and adolescents with HIV infection and first-line treatment failure to receive a ritonavir-boosted protease inhibitor (lopinavir-ritonavir) plus clinician-selected NRTIs (NRTI group, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison (raltegravir group, 433 patients), or protease-inhibitor monotherapy after 12 weeks of induction therapy with raltegravir in a noninferiority comparison (monotherapy group, 418 patients). The primary composite end point, good HIV disease control, was defined as survival with no new World Health Organization stage 4 events, a CD4+ count of more than 250 cells per cubic millimeter, and a viral load of less than 10,000 copies per milliliter or 10,000 copies or more with no protease resistance mutations at week 96 and was analyzed with the use of imputation of data (≤4%). Good HIV disease control was achieved in 60% of the patients (mean, 255 patients) in the NRTI group, 64% of the patients (mean, 277) in the raltegravir group (P=0.21 for the comparison with the NRTI group; superiority of raltegravir not shown), and 55% of the patients (mean, 232) in the monotherapy group (noninferiority of monotherapy not shown, based on a 10-percentage-point margin). There was no significant difference in rates of grade 3 or 4 adverse events among the three groups (P=0.82). The viral load was less than 400 copies per milliliter in 86% of patients in the NRTI group, 86% in the raltegravir group (P=0.97), and 61% in the monotherapy group (P<0.001). When given with a protease inhibitor in second-line therapy, NRTIs retained substantial virologic activity without evidence of increased toxicity, and there was no advantage to replacing them with raltegravir. Virologic control was inferior with protease-inhibitor monotherapy. (Funded by European and Developing Countries Clinical Trials Partnership and others; EARNEST Current Controlled Trials number, ISRCTN37737787, and ClinicalTrials.gov number, NCT00988039.).

Diet, physical activity and behavioural interventions for the treatment of overweight or obese adolescents aged 12 to 17 years.

PubMed

Al-Khudairy, Lena; Loveman, Emma; Colquitt, Jill L; Mead, Emma; Johnson, Rebecca E; Fraser, Hannah; Olajide, Joan; Murphy, Marie; Velho, Rochelle Marian; O'Malley, Claire; Azevedo, Liane B; Ells, Louisa J; Metzendorf, Maria-Inti; Rees, Karen

2017-06-22

Adolescent overweight and obesity has increased globally, and can be associated with short- and long-term health consequences. Modifying known dietary and behavioural risk factors through behaviour changing interventions (BCI) may help to reduce childhood overweight and obesity. This is an update of a review published in 2009. To assess the effects of diet, physical activity and behavioural interventions for the treatment of overweight or obese adolescents aged 12 to 17 years. We performed a systematic literature search in: CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, and the trial registers ClinicalTrials.gov and ICTRP Search Portal. We checked references of identified studies and systematic reviews. There were no language restrictions. The date of the last search was July 2016 for all databases. We selected randomised controlled trials (RCTs) of diet, physical activity and behavioural interventions for treating overweight or obesity in adolescents aged 12 to 17 years. Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using the GRADE instrument and extracted data following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. We included 44 completed RCTs (4781 participants) and 50 ongoing studies. The number of participants in each trial varied (10 to 521) as did the length of follow-up (6 to 24 months). Participants ages ranged from 12 to 17.5 years in all trials that reported mean age at baseline. Most of the trials used a multidisciplinary intervention with a combination of diet, physical activity and behavioural components. The content and duration of the intervention, its delivery and the comparators varied across trials. The studies contributing most information to outcomes of weight and body mass index (BMI) were from studies at a low risk of bias, but studies with a high risk of bias provided data on adverse events and quality of life.The mean difference (MD) of the change in BMI at the longest follow-up period in favour of BCI was -1.18 kg/m 2 (95% confidence interval (CI) -1.67 to -0.69); 2774 participants; 28 trials; low quality evidence. BCI lowered the change in BMI z score by -0.13 units (95% CI -0.21 to -0.05); 2399 participants; 20 trials; low quality evidence. BCI lowered body weight by -3.67 kg (95% CI -5.21 to -2.13); 1993 participants; 20 trials; moderate quality evidence. The effect on weight measures persisted in trials with 18 to 24 months' follow-up for both BMI (MD -1.49 kg/m 2 (95% CI -2.56 to -0.41); 760 participants; 6 trials and BMI z score MD -0.34 (95% CI -0.66 to -0.02); 602 participants; 5 trials).There were subgroup differences showing larger effects for both BMI and BMI z score in studies comparing interventions with no intervention/wait list control or usual care, compared with those testing concomitant interventions delivered to both the intervention and control group. There were no subgroup differences between interventions with and without parental involvement or by intervention type or setting (health care, community, school) or mode of delivery (individual versus group).The rate of adverse events in intervention and control groups was unclear with only five trials reporting harms, and of these, details were provided in only one (low quality evidence). None of the included studies reported on all-cause mortality, morbidity or socioeconomic effects.BCIs at the longest follow-up moderately improved adolescent's health-related quality of life (standardised mean difference 0.44 ((95% CI 0.09 to 0.79); P = 0.01; 972 participants; 7 trials; 8 comparisons; low quality of evidence) but not self-esteem.Trials were inconsistent in how they measured dietary intake, dietary behaviours, physical activity and behaviour. We found low quality evidence that multidisciplinary interventions involving a combination of diet, physical activity and behavioural components reduce measures of BMI and moderate quality evidence that they reduce weight in overweight or obese adolescents, mainly when compared with no treatment or waiting list controls. Inconsistent results, risk of bias or indirectness of outcome measures used mean that the evidence should be interpreted with caution. We have identified a large number of ongoing trials (50) which we will include in future updates of this review.

Changes in body composition over 8 years in a randomized trial of a lifestyle intervention: the look AHEAD study.

PubMed

Pownall, Henry J; Bray, George A; Wagenknecht, Lynne E; Walkup, Michael P; Heshka, Stanley; Hubbard, Van S; Hill, James; Kahn, Steven E; Nathan, David M; Schwartz, Anne V; Johnson, Karen C

2015-03-01

To determine the effects of an intensive lifestyle intervention versus a comparison group on body composition in obese or overweight persons with type 2 diabetes at baseline and at 1, 4, and 8 years. Body composition was measured by dual-energy X-ray absorptiometry in a subset of 1019 Look AHEAD study volunteers randomized to intervention or comparison groups. The intervention was designed to achieve and maintain ≥7% weight loss through increased physical activity and reduced caloric intake. The comparison group received social support and diabetes education. At 1 year, the intervention group lost fat (5.6 ± 0.2 kg) and lean mass (2.3 ± 0.1 kg) but regained fat (∼100%) and lost lean mass between years 1 and 8. Between baseline and year 8, weight loss was greater in intervention versus comparison groups (4.0 ± 0.4 vs. 2.3 ± 0.4 kg); comparison group weight loss was mostly lean mass (2.1 ± 0.17 kg). Fat mass in the intervention group was lower than that of the comparison group at all post-baseline time points. Reduced fat mass may place the intervention group at a lower risk of obesity-linked sequelae, a hypothesis that can be tested by future studies of this cohort. © 2015 The Obesity Society.

Vitamin C for preventing and treating the common cold.

PubMed

Hemilä, Harri; Chalker, Elizabeth

2013-01-31

Vitamin C (ascorbic acid) for preventing and treating the common cold has been a subject of controversy for 70 years. To find out whether vitamin C reduces the incidence, the duration or severity of the common cold when used either as a continuous regular supplementation every day or as a therapy at the onset of cold symptoms. We searched CENTRAL 2012, Issue 11, MEDLINE (1966 to November week 3, 2012), EMBASE (1990 to November 2012), CINAHL (January 2010 to November 2012), LILACS (January 2010 to November 2012) and Web of Science (January 2010 to November 2012). We also searched the U.S. National Institutes of Health trials register and WHO ICTRP on 29 November 2012. We excluded trials which used less than 0.2 g per day of vitamin C and trials without a placebo comparison. We restricted our review to placebo-controlled trials. Two review authors independently extracted data. We assessed 'incidence' of colds during regular supplementation as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean number of days of illness of cold episodes. Twenty-nine trial comparisons involving 11,306 participants contributed to the meta-analysis on the risk ratio (RR) of developing a cold whilst taking vitamin C regularly over the study period. In the general community trials involving 10,708 participants, the pooled RR was 0.97 (95% confidence interval (CI) 0.94 to 1.00). Five trials involving a total of 598 marathon runners, skiers and soldiers on subarctic exercises yielded a pooled RR of 0.48 (95% CI 0.35 to 0.64).Thirty-one comparisons examined the effect of regular vitamin C on common cold duration (9745 episodes). In adults the duration of colds was reduced by 8% (3% to 12%) and in children by 14% (7% to 21%). In children, 1 to 2 g/day vitamin C shortened colds by 18%. The severity of colds was also reduced by regular vitamin C administration.Seven comparisons examined the effect of therapeutic vitamin C (3249 episodes). No consistent effect of vitamin C was seen on the duration or severity of colds in the therapeutic trials.The majority of included trials were randomised, double-blind trials. The exclusion of trials that were either not randomised or not double-blind had no effect on the conclusions. The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified, yet vitamin C may be useful for people exposed to brief periods of severe physical exercise. Regular supplementation trials have shown that vitamin C reduces the duration of colds, but this was not replicated in the few therapeutic trials that have been carried out. Nevertheless, given the consistent effect of vitamin C on the duration and severity of colds in the regular supplementation studies, and the low cost and safety, it may be worthwhile for common cold patients to test on an individual basis whether therapeutic vitamin C is beneficial for them. Further therapeutic RCTs are warranted.

Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials

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

Ramroth, Johanna; Cutter, David J.; Darby, Sarah C.

Purpose: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Methods and Materials: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. Results: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, highermore » versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). Conclusions: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no upper dose level was found above which there was no further benefit. These findings support the consideration of further radiation therapy dose escalation trials, making use of modern treatment methods to reduce toxicity.« less

A scoping review of indirect comparison methods and applications using individual patient data.

PubMed

Veroniki, Areti Angeliki; Straus, Sharon E; Soobiah, Charlene; Elliott, Meghan J; Tricco, Andrea C

2016-04-27

Several indirect comparison methods, including network meta-analyses (NMAs), using individual patient data (IPD) have been developed to synthesize evidence from a network of trials. Although IPD indirect comparisons are published with increasing frequency in health care literature, there is no guidance on selecting the appropriate methodology and on reporting the methods and results. In this paper we examine the methods and reporting of indirect comparison methods using IPD. We searched MEDLINE, Embase, the Cochrane Library, and CINAHL from inception until October 2014. We included published and unpublished studies reporting a method, application, or review of indirect comparisons using IPD and at least three interventions. We identified 37 papers, including a total of 33 empirical networks. Of these, only 9 (27 %) IPD-NMAs reported the existence of a study protocol, whereas 3 (9 %) studies mentioned that protocols existed without providing a reference. The 33 empirical networks included 24 (73 %) IPD-NMAs and 9 (27 %) matching adjusted indirect comparisons (MAICs). Of the 21 (64 %) networks with at least one closed loop, 19 (90 %) were IPD-NMAs, 13 (68 %) of which evaluated the prerequisite consistency assumption, and only 5 (38 %) of the 13 IPD-NMAs used statistical approaches. The median number of trials included per network was 10 (IQR 4-19) (IPD-NMA: 15 [IQR 8-20]; MAIC: 2 [IQR 3-5]), and the median number of IPD trials included in a network was 3 (IQR 1-9) (IPD-NMA: 6 [IQR 2-11]; MAIC: 2 [IQR 1-2]). Half of the networks (17; 52 %) applied Bayesian hierarchical models (14 one-stage, 1 two-stage, 1 used IPD as an informative prior, 1 unclear-stage), including either IPD alone or with aggregated data (AD). Models for dichotomous and continuous outcomes were available (IPD alone or combined with AD), as were models for time-to-event data (IPD combined with AD). One in three indirect comparison methods modeling IPD adjusted results from different trials to estimate effects as if they had come from the same, randomized, population. Key methodological and reporting elements (e.g., evaluation of consistency, existence of study protocol) were often missing from an indirect comparison paper.

A Bayesian pick-the-winner design in a randomized phase II clinical trial.

PubMed

Chen, Dung-Tsa; Huang, Po-Yu; Lin, Hui-Yi; Chiappori, Alberto A; Gabrilovich, Dmitry I; Haura, Eric B; Antonia, Scott J; Gray, Jhanelle E

2017-10-24

Many phase II clinical trials evaluate unique experimental drugs/combinations through multi-arm design to expedite the screening process (early termination of ineffective drugs) and to identify the most effective drug (pick the winner) to warrant a phase III trial. Various statistical approaches have been developed for the pick-the-winner design but have been criticized for lack of objective comparison among the drug agents. We developed a Bayesian pick-the-winner design by integrating a Bayesian posterior probability with Simon two-stage design in a randomized two-arm clinical trial. The Bayesian posterior probability, as the rule to pick the winner, is defined as probability of the response rate in one arm higher than in the other arm. The posterior probability aims to determine the winner when both arms pass the second stage of the Simon two-stage design. When both arms are competitive (i.e., both passing the second stage), the Bayesian posterior probability performs better to correctly identify the winner compared with the Fisher exact test in the simulation study. In comparison to a standard two-arm randomized design, the Bayesian pick-the-winner design has a higher power to determine a clear winner. In application to two studies, the approach is able to perform statistical comparison of two treatment arms and provides a winner probability (Bayesian posterior probability) to statistically justify the winning arm. We developed an integrated design that utilizes Bayesian posterior probability, Simon two-stage design, and randomization into a unique setting. It gives objective comparisons between the arms to determine the winner.

Effective behaviour change techniques in the prevention and management of childhood obesity.

PubMed

Martin, J; Chater, A; Lorencatto, F

2013-10-01

Rates of childhood obesity are increasing, and it is essential to identify the active components of interventions aiming to prevent and manage obesity in children. A systematic review of behaviour change interventions was conducted to find evidence of behaviour change techniques (BCTs) that are most effective in changing physical activity and/or eating behaviour for the prevention or management of childhood obesity. An electronic search was conducted for randomised controlled trials published between January 1990 and December 2009. Of 4309 titles and abstracts screened, full texts of 135 articles were assessed, of which 17 published articles were included in this review. Intervention descriptions were coded according to the behaviour-specific CALO-RE taxonomy of BCTs. BCTs were identified and compared across obesity management (n=9) vs prevention (n=8) trials. To assess the effectiveness of individual BCTs, trials were further divided into those that were effective (defined as either a group reduction of at least 0.13 body mass index (BMI) units or a significant difference in BMI between intervention and control groups at follow-up) vs non-effective (reported no significant differences between groups). We reliably identified BCTs utilised in effective and non-effective prevention and management trials. To illustrate the relative effectiveness of each BCT, effectiveness ratios were calculated as the ratio of the number of times each BCT was a component of an intervention in an effective trial divided by the number of times they were a component of all trials. Results indicated six BCTs that may be effective components of future management interventions (provide information on the consequences of behaviour to the individual, environmental restructuring, prompt practice, prompt identification as role model/position advocate, stress management/emotional control training and general communication skills training), and one that may be effective in prevention interventions (prompting generalisation of a target behaviour). We identified that for management trials, providing information on the consequences of behaviour in general was a feature of non-effective interventions and for prevention trials, providing information on the consequences of behaviour in general, providing rewards contingent on successful behaviour and facilitating social comparison were non-effective. To design effective behaviour change programmes for the prevention and management of childhood obesity, we would recommend utilising the BCTs identified as effective in this review. The impact on intervention effectiveness of combining BCTs should be the topic of further research.

Effects of lemon verbena extract (Recoverben®) supplementation on muscle strength and recovery after exhaustive exercise: a randomized, placebo-controlled trial.

PubMed

Buchwald-Werner, Sybille; Naka, Ioanna; Wilhelm, Manfred; Schütz, Elivra; Schoen, Christiane; Reule, Claudia

2018-01-01

Exhaustive exercise causes muscle damage accompanied by oxidative stress and inflammation leading to muscle fatigue and muscle soreness. Lemon verbena leaves, commonly used as tea and refreshing beverage, demonstrated antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of a proprietary lemon verbena extract (Recoverben®) on muscle strength and recovery after exhaustive exercise in comparison to a placebo product. The study was performed as a randomized, placebo-controlled, double-blind study with parallel design. Forty-four healthy males and females, which were 22-50 years old and active in sports, were randomized to 400 mg lemon verbena extract once daily or placebo. The 15 days intervention was divided into 10 days supplementation prior to the exhaustive exercise day (intensive jump-protocol), one day during the test and four days after. Muscle strength (MVC), muscle damage (CK), oxidative stress (GPx), inflammation (IL6) and volunteer-reported muscle soreness intensity were assessed pre and post exercise. Participants in the lemon verbena group benefited from less muscle damage as well as faster and full recovery. Compared to placebo, lemon verbena extract receiving participants had significantly less exercise-related loss of muscle strength ( p  = 0.0311) over all timepoints, improved glutathione peroxidase activity by trend ( p  = 0.0681) and less movement induced pain ( p  = 0.0788) by trend. Creatine kinase and IL-6 didn't show significant discrimmination between groups. Lemon verbena extract (Recoverben®) has been shown to be a safe and well-tolerated natural sports ingredient, by reducing muscle damage after exhaustive exercise. The trial was registered in the clinical trials registry (clinical trial.gov NCT02923102). Registered 28 September 2016.

Life-science research within US academic medical centers.

PubMed

Zinner, Darren E; Campbell, Eric G

2009-09-02

Besides the generic "basic" vs "applied" labels, little information is known about the types of life-science research conducted within academic medical centers (AMCs). To determine the relative proportion, characteristics, funding, and productivity of AMC faculty by the type of research they conduct. Mailed survey conducted in 2007 of 3080 life-science faculty at the 50 universities with medical schools that received the most funding from the National Institutes of Health in 2004. Response rate was 74%. Research faculty affiliated with a medical school or teaching hospital, representing 77% of respondents (n = 1663). Type of research (basic, translational, clinical trials, health services research/clinical epidemiology, multimode, other), total funding, industry funding, publications, professional activities, patenting behavior, and industry relationships. Among AMC research faculty, 33.6% exclusively conducted basic science research as principal investigators compared with translational researchers (9.1%), clinical trial investigators (7.1%), and health services researchers/clinical epidemiologists (9.0%). While principal investigators garnered a mean of $410,755 in total annual research funding, 22.1% of all AMC research faculty were unsponsored, a proportion that ranged from 11.5% for basic science researchers to 46.8% for health services researchers (P < .001). The average AMC faculty member received $33,417 in industry-sponsored funding, with most of this money concentrated among clinical trial ($110,869) and multimode ($59,916) principal investigators. Translational (61.3%), clinical trial (67.3%), and multimode (70.9%) researchers were significantly more likely than basic science researchers (41.9%) to report a relationship with industry and that these relationships contributed to their most important scientific work (P < .05 for all comparisons). The research function of AMCs is active and diverse, incorporating a substantial proportion of faculty who are conducting research and publishing without sponsorship.

Acellular pertussis vaccines--a question of efficacy.

PubMed

Olin, P

1995-06-01

Whole cell pertussis vaccine is considered to offer at least 80% protection against typical whooping cough. The quest for an equally effective but less reactogenic vaccine is now drawing to a close. During the forthcoming year a number of efficacy trials of acellular pertussis vaccines will be terminated. A variety of vaccines containing one, two, three or five purified pertussis antigens are being tested in Germany, Italy, Senegal and Sweden. About 30,000 infants have been enrolled in placebo-controlled studies and more than 100,000 in whole cell vaccine-controlled trials. The final plans for analysis of a Swedish placebo-controlled trial of whole cell and acellular vaccines is presented. Due to the unexpected high incidence of pertussis in Sweden during 1993-1994, relative risk comparisons between vaccines will be attempted in that trial, in addition to estimating absolute efficacy. A crucial issue is to what extent data may be compared between trials, given differences in design, vaccination schedules, and chosen endpoints. A primary case definition of laboratory-confirmed pertussis with at least 21 days of paroxysmal cough have been adopted in most trials. Pre-planned meta-analysis using this single endpoint will facilitate comparisons between vaccines. Serological correlates to protection in individuals will be sought in the ongoing placebo-controlled trials. The concept of a serological correlate valid for a vaccinated population but not necessarily for the vaccinated individual, as is the case with Hib vaccines, may turn out to be the only alternative to performing large efficacy trials in the future.

Wearable activity monitors in oncology trials: Current use of an emerging technology.

PubMed

Gresham, Gillian; Schrack, Jennifer; Gresham, Louise M; Shinde, Arvind M; Hendifar, Andrew E; Tuli, Richard; Rimel, B J; Figlin, Robert; Meinert, Curtis L; Piantadosi, Steven

2018-01-01

Physical activity is an important outcome in oncology trials. Physical activity is commonly assessed using self-reported questionnaires, which are limited by recall and response biases. Recent advancements in wearable technology have provided oncologists with new opportunities to obtain real-time, objective physical activity data. The purpose of this review was to describe current uses of wearable activity monitors in oncology trials. We searched Pubmed, Embase, and the Cochrane Central Register of Controlled Trials for oncology trials involving wearable activity monitors published between 2005 and 2016. We extracted details on study design, types of activity monitors used, and purpose for their use. We summarized activity monitor metrics including step counts, sleep and sedentary time, and time spent in moderate-to-vigorous activity. We identified 41 trials of which 26 (63%) involved cancer survivors (post-treatment) and 15 trials (37%) involved patients with active cancer. Most trials (65%) involved breast cancer patients. Wearable activity monitors were commonly used in exercise (54%) or behavioral (29%) trials. Cancer survivors take between 4660 and 11,000 steps/day and those undergoing treatment take 2885 to 8300steps/day. Wearable activity monitors are increasingly being used to obtain objective measures of physical activity in oncology trials. There is potential for their use to expand to evaluate and predict clinical outcomes such as survival, quality of life, and treatment tolerance in future studies. Currently, there remains a lack of standardization in the types of monitors being used and how their data are being collected, analyzed, and interpreted. Recent advancements in wearable activity monitor technology have provided oncologists with new opportunities to monitor their patients' daily activity in real-world settings. The integration of wearable activity monitors into cancer care will help increase our understanding of the associations between physical activity and the prevention and management of the disease, in addition to other important cancer outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Average is optimal: an inverted-U relationship between trial-to-trial brain activity and behavioral performance.

PubMed

He, Biyu J; Zempel, John M

2013-01-01

It is well known that even under identical task conditions, there is a tremendous amount of trial-to-trial variability in both brain activity and behavioral output. Thus far the vast majority of event-related potential (ERP) studies investigating the relationship between trial-to-trial fluctuations in brain activity and behavioral performance have only tested a monotonic relationship between them. However, it was recently found that across-trial variability can correlate with behavioral performance independent of trial-averaged activity. This finding predicts a U- or inverted-U- shaped relationship between trial-to-trial brain activity and behavioral output, depending on whether larger brain variability is associated with better or worse behavior, respectively. Using a visual stimulus detection task, we provide evidence from human electrocorticography (ECoG) for an inverted-U brain-behavior relationship: When the raw fluctuation in broadband ECoG activity is closer to the across-trial mean, hit rate is higher and reaction times faster. Importantly, we show that this relationship is present not only in the post-stimulus task-evoked brain activity, but also in the pre-stimulus spontaneous brain activity, suggesting anticipatory brain dynamics. Our findings are consistent with the presence of stochastic noise in the brain. They further support attractor network theories, which postulate that the brain settles into a more confined state space under task performance, and proximity to the targeted trajectory is associated with better performance.

Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials.

PubMed

Strand, Vibeke; Ahadieh, Sima; French, Jonathan; Geier, Jamie; Krishnaswami, Sriram; Menon, Sujatha; Checchio, Tina; Tensfeldt, Thomas G; Hoffman, Elaine; Riese, Richard; Boy, Mary; Gómez-Reino, Juan J

2015-12-15

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to lymphocyte activation, proliferation, and function. Thus, tofacitinib therapy may result in suppression of multiple elements of the immune response. Serious infections have been reported in tofacitinib RA trials. However, limited head-to-head comparator data were available within the tofacitinib RA development program to directly compare rates of serious infections with tofacitinib relative to biologic agents, and specifically adalimumab (employed as an active control agent in two randomized controlled trials of tofacitinib). A systematic literature search of data from interventional randomized controlled trials and long-term extension studies with biologics in RA was carried out. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results of the review and meta-analysis. Incidence rates (unique patients with events/100 patient-years) for each therapy were estimated based on data from randomized controlled trials and long-term extension studies using a random-effects model. Relative and absolute risk comparisons versus placebo used Mantel-Haenszel methods. The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95% confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95% CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38% (-0.24%, 0.99%) and 0.40% (-0.22%, 1.02%), respectively. In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA.

Cerebellar subjects show impaired adaptation of anticipatory EMG during catching.

PubMed

Lang, C E; Bastian, A J

1999-11-01

We evaluated the role of the cerebellum in adapting anticipatory muscle activity during a multijointed catching task. Individuals with and without cerebellar damage caught a series of balls of different weights dropped from above. In Experiment 1 (light-heavy-light), each subject was required to catch light balls (baseline phase), heavy balls (adaptation phase), and then light balls again (postadaptation phase). Subjects were not told when the balls would be switched, and they were required to keep their hand within a vertical spatial "window" during the catch. During the series of trials, we measured three-dimensional (3-D) position and electromyogram (EMG) from the catching arm. We modeled the adaptation process using an exponential decay function; this model allowed us to dissociate adaptation from performance variability. Results from the position data show that cerebellar subjects did not adapt or adapted very slowly to the changed ball weight when compared with the control subjects. The cerebellar group required an average of 30.9 +/- 8.7 trials (mean +/- SE) to progress approximately two-thirds of the way through the adaptation compared with 1.7 +/- 0.2 trials for the control group. Only control subjects showed a negative aftereffect indicating storage of the adaptation. No difference in performance variability existed between the two groups. EMG data show that control subjects increased their anticipatory muscle activity in the flexor muscles of the arm to control the momentum of the ball at impact. Cerebellar subjects were unable to differentially increase the anticipatory muscle activity across three joints to perform the task successfully. In Experiment 2 (heavy-light-heavy), we tested to see whether the rate of adaptation changed when adapting to a light ball versus a heavy ball. Subjects caught the heavy balls (baseline phase), the light balls (adaptation phase), and then heavy balls again (postadaptation phase). Comparison of rates of adaptation between Experiment 1 and Experiment 2 showed that the rate of adaptation was unchanged whether adapting to a light ball or a heavy ball. Given these findings, we conclude that the cerebellum is important in generating the appropriate anticipatory muscle activity across multiple muscles and modifying it in response to changing demands though trial-and-error practice.

Comparison of rumination activity measured using rumination collars against direct visual observations and analysis of video recordings of dairy cows in commercial farm environments.

PubMed

Ambriz-Vilchis, V; Jessop, N S; Fawcett, R H; Shaw, D J; Macrae, A I

2015-03-01

Automated systems for monitoring the behavior of cows have become increasingly important for management routines and for monitoring health and welfare. In the past few decades, various devices that record rumination have been developed. The aim of the present study was to compare rumination activity measured with a commercially available rumination collar (RC) against that obtained by direct visual observations and analysis of video recordings in commercial dairy cows. Rumination time from video recordings was recorded by a trained observer. To assess observer reliability, data were recorded twice, and the duration of recorded behaviors was very similar and highly correlated between these 2 measurements (mean=39±4 and 38±4 min/2 h). Measurements of rumination time obtained with RC when compared with analysis of video recordings and direct observations were variable: RC output was significantly positively related to observed rumination activity when dealing with animals housed indoors (trial 1 video recordings: slope=1.02, 95% CI=0.92-1.12), and the limits of agreement method (LoA) showed differences (in min per 2-h block) to be within -26.92 lower and 24.27 upper limits. Trial 1 direct observations: slope=1.08, 95% CI=0.62-1.55, and the LoA showed differences to be within -28.54 lower and 21.98 upper limits. Trial 2: slope=0.93, 95% CI=0.64-1.23, and the LoA showed differences to be within -32.56 lower and 19.84 upper limits. However, the results were poor when cows were outside grazing grass (trial 3: slope=0.57, 95% CI=0.13-1.02, and the LoA showed differences to be within wider limits -51.16 lower and 53.02 upper). Our results suggest that RC can determine rumination activity and are an alternative to visual observations when animals are housed indoors. However, they are not an alternative to direct observations with grazing animals on pasture and its use is not advisable until further research and validation are carried out. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A phase 2 trial of dasatinib in patients with locally advanced or stage IV mucosal, acral, or vulvovaginal melanoma: A trial of the ECOG-ACRIN Cancer Research Group (E2607).

PubMed

Kalinsky, Kevin; Lee, Sandra; Rubin, Krista M; Lawrence, Donald P; Iafrarte, Anthony J; Borger, Darell R; Margolin, Kim A; Leitao, Mario M; Tarhini, Ahmad A; Koon, Henry B; Pecora, Andrew L; Jaslowski, Anthony J; Cohen, Gary I; Kuzel, Timothy M; Lao, Christopher D; Kirkwood, John M

2017-07-15

KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11 L576P . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes. Patients received 70 mg of oral dasatinib twice daily. The primary objective for this 2-stage phase 2 trial was response rate. Stage I was open to KIT+ and wild-type KIT (KIT-) mucosal, acral, and CSD melanoma (n = 57). Stage II accrued only KIT+ tumors (n = 30). To enrich the trial for KIT+ tumors, vulvovaginal melanoma was added, and CSD melanoma was removed from eligibility. Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety. From May 2009 to December 2010, the first stage enrolled 57 patients. Among the evaluable patients, 3 of 51 (5.9%) achieved a partial response: all were KIT-. Stage II closed early because of slow accrual (November 2011 to December 2015). In stage II, 4 of 22 evaluable patients (18.2%) had a partial response; the median duration was 4.2 months. The median PFS was 2.1 months (n = 73; 95% confidence interval [CI], 1.5-2.9 months). The median OS was 7.5 months (95% CI, 6.0-11.9 months). In exploratory analyses, no differences were seen in PFS or OS with the KIT status or subtype. Dasatinib was discontinued because of adverse events in 9 of 75 patients (12%). The dasatinib response rate among KIT+ melanoma patients was low. In view of its clinical activity, it is recommended that imatinib remain the KIT tyrosine kinase inhibitor of choice for unresectable KIT+ melanoma. Cancer 2017;123:2688-97. © 2017 American Cancer Society. © 2017 American Cancer Society.

Microwave ablation devices for interventional oncology.

PubMed

Ward, Robert C; Healey, Terrance T; Dupuy, Damian E

2013-03-01

Microwave ablation is one of the several options in the ablation armamentarium for the treatment of malignancy, offering several potential benefits when compared with other ablation, radiation, surgical and medical treatment modalities. The basic microwave system consists of the generator, power distribution system and antennas. Often under image (computed tomography or ultrasound) guidance, a needle-like antenna is inserted percutaneously into the tumor, where local microwave electromagnetic radiation is emitted from the probe's active tip, producing frictional tissue heating, capable of causing cell death by coagulation necrosis. Half of the microwave ablation systems use a 915 MHz generator and the other half use a 2450 MHz generator. To date, there are no completed clinical trials comparing microwave devices head-to-head. Prospective comparisons of microwave technology with other treatment alternatives, as well as head-to-head comparison with each microwave device, is needed if this promising field will garner more widespread support and use in the oncology community.

"Meta-Analysis of Dropout in Treatments for Posttraumatic Stress Disorder": Correction to Imel et al. (2013).

PubMed

2016-09-01

Reports an error in "Meta-analysis of dropout in treatments for posttraumatic stress disorder" by Zac E. Imel, Kevin Laska, Matthew Jakupcak and Tracy L. Simpson ( Journal of Consulting and Clinical Psychology , 2013[Jun], Vol 81[3], 394-404). There are two errors in the Results section. Each is described alongside the corrected results. Corrections did not influence interpretation of the results. Neither the magnitude of effects nor statistical significance of any results is substantively altered. (The following abstract of the original article appeared in record 2013-01522-001.) Objective: Many patients drop out of treatments for posttraumatic stress disorder (PTSD); some clinicians believe that trauma-focused treatments increase dropout. We conducted a meta-analysis of dropout among active treatments in clinical trials for PTSD (42 studies; 17 direct comparisons). The average dropout rate was 18%, but it varied significantly across studies. Group modality and greater number of sessions, but not trauma focus, predicted increased dropout. When the meta-analysis was restricted to direct comparisons of active treatments, there were no differences in dropout. Differences in trauma focus between treatments in the same study did not predict dropout. However, trauma-focused treatments resulted in higher dropout compared with present-centered therapy (PCT), a treatment originally designed as a control but now listed as a research-supported intervention for PTSD. Dropout varies between active interventions for PTSD across studies, but variability is primarily driven by differences between studies. There do not appear to be systematic differences across active interventions when they are directly compared in the same study. The degree of clinical attention placed on the traumatic event does not appear to be a primary cause of dropout from active treatments. However, comparisons of PCT may be an exception to this general pattern, perhaps because of a restriction of variability in trauma focus among comparisons of active treatments. More research is needed comparing trauma-focused interventions to trauma-avoidant treatments such as PCT. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Incorporating multiple secondary targets into learning trials for individuals with autism spectrum disorder.

PubMed

Nottingham, Casey L; Vladescu, Jason C; Kodak, Tiffany; Kisamore, April N

2017-07-01

The current study examined the outcome of presenting multiple secondary targets in learning trials for individuals with autism spectrum disorder. We compared conditions in which (a) a secondary target was presented in the antecedent and consequence of trials, (b) two secondary targets were presented in the consequence of trials, (c) one secondary target was presented in the consequence of each trial, and (d) no additional targets were presented trials. The participants acquired the majority of secondary targets. Presenting one or multiple secondary targets per trial, regardless of the location of these secondary targets, increased the efficiency of instruction in comparison to a condition with no secondary target. © 2017 Society for the Experimental Analysis of Behavior.

Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults.

PubMed

Costello, Joseph T; Baker, Philip R A; Minett, Geoffrey M; Bieuzen, Francois; Stewart, Ian B; Bleakley, Chris

2015-09-18

Recovery strategies are often used with the intention of preventing or minimising muscle soreness after exercise. Whole-body cryotherapy, which involves a single or repeated exposure(s) to extremely cold dry air (below -100 °C) in a specialised chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise. To assess the effects (benefits and harms) of whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the British Nursing Index and the Physiotherapy Evidence Database. We also searched the reference lists of articles, trial registers and conference proceedings, handsearched journals and contacted experts.The searches were run in August 2015. We aimed to include randomised and quasi-randomised trials that compared the use of whole-body cryotherapy (WBC) versus a passive or control intervention (rest, no treatment or placebo treatment) or active interventions including cold or contrast water immersion, active recovery and infrared therapy for preventing or treating muscle soreness after exercise in adults. We also aimed to include randomised trials that compared different durations or dosages of WBC. Our prespecified primary outcomes were muscle soreness, subjective recovery (e.g. tiredness, well-being) and adverse effects. Two review authors independently screened search results, selected studies, assessed risk of bias and extracted and cross-checked data. Where appropriate, we pooled results of comparable trials. The random-effects model was used for pooling where there was substantial heterogeneity. We assessed the quality of the evidence using GRADE. Four laboratory-based randomised controlled trials were included. These reported results for 64 physically active predominantly young adults (mean age 23 years). All but four participants were male. Two trials were parallel group trials (44 participants) and two were cross-over trials (20 participants). The trials were heterogeneous, including the type, temperature, duration and frequency of WBC, and the type of preceding exercise. None of the trials reported active surveillance of predefined adverse events. All four trials had design features that carried a high risk of bias, potentially limiting the reliability of their findings. The evidence for all outcomes was classified as 'very low' quality based on the GRADE criteria.Two comparisons were tested: WBC versus control (rest or no WBC), tested in four studies; and WBC versus far-infrared therapy, also tested in one study. No studies compared WBC with other active interventions, such as cold water immersion, or different types and applications of WBC.All four trials compared WBC with rest or no WBC. There was very low quality evidence for lower self-reported muscle soreness (pain at rest) scores after WBC at 1 hour (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -1.42 to -0.12; 20 participants, 2 cross-over trials); 24 hours (SMD -0.57, 95% CI -1.48 to 0.33) and 48 hours (SMD -0.58, 95% CI -1.37 to 0.21), both with 38 participants, 2 cross-over studies, 1 parallel group study; and 72 hours (SMD -0.65, 95% CI -2.54 to 1.24; 29 participants, 1 cross-over study, 1 parallel group study). Of note is that the 95% CIs also included either no between-group differences or a benefit in favour of the control group. One small cross-over trial (9 participants) found no difference in tiredness but better well-being after WBC at 24 hours post exercise. There was no report of adverse events.One small cross-over trial involving nine well-trained runners provided very low quality evidence of lower levels of muscle soreness after WBC, when compared with infrared therapy, at 1 hour follow-up, but not at 24 or 48 hours. The same trial found no difference in well-being but less tiredness after WBC at 24 hours post exercise. There was no report of adverse events. There is insufficient evidence to determine whether whole-body cryotherapy (WBC) reduces self-reported muscle soreness, or improves subjective recovery, after exercise compared with passive rest or no WBC in physically active young adult males. There is no evidence on the use of this intervention in females or elite athletes. The lack of evidence on adverse events is important given that the exposure to extreme temperature presents a potential hazard. Further high-quality, well-reported research in this area is required and must provide detailed reporting of adverse events.

A Multisite, Randomized Controlled Clinical Trial of Computerized Cognitive Remediation Therapy for Schizophrenia.

PubMed

Gomar, Jesús J; Valls, Elia; Radua, Joaquim; Mareca, Celia; Tristany, Josep; del Olmo, Francisco; Rebolleda-Gil, Carlos; Jañez-Álvarez, María; de Álvaro, Francisco J; Ovejero, María R; Llorente, Ana; Teixidó, Cristina; Donaire, Ana M; García-Laredo, Eduardo; Lazcanoiturburu, Andrea; Granell, Luis; Mozo, Cristina de Pablo; Pérez-Hernández, Mónica; Moreno-Alcázar, Ana; Pomarol-Clotet, Edith; McKenna, Peter J

2015-11-01

The effectiveness of cognitive remediation therapy (CRT) for the neuropsychological deficits seen in schizophrenia is supported by meta-analysis. However, a recent methodologically rigorous trial had negative findings. In this study, 130 chronic schizophrenic patients were randomly assigned to computerized CRT, an active computerized control condition (CC) or treatment as usual (TAU). Primary outcome measures were 2 ecologically valid batteries of executive function and memory, rated under blind conditions; other executive and memory tests and a measure of overall cognitive function were also employed. Carer ratings of executive and memory failures in daily life were obtained before and after treatment. Computerized CRT was found to produce improvement on the training tasks, but this did not transfer to gains on the primary outcome measures and most other neuropsychological tests in comparison to either CC or TAU conditions. Nor did the intervention result in benefits on carer ratings of daily life cognitive failures. According to this study, computerized CRT is not effective in schizophrenia. The use of both active and passive CCs suggests that nature of the control group is not an important factor influencing results. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Relaxation techniques for pain management in labour.

PubMed

Smith, Caroline A; Levett, Kate M; Collins, Carmel T; Armour, Mike; Dahlen, Hannah G; Suganuma, Machiko

2018-03-28

Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute to the popularity of complementary methods of pain management. This review examined currently available evidence on the use of relaxation therapies for pain management in labour. This is an update of a review first published in 2011. To examine the effects of mind-body relaxation techniques for pain management in labour on maternal and neonatal well-being during and after labour. We searched Cochrane Pregnancy and Childbirth's Trials Register (9 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 5 2017), MEDLINE (1966 to 24 May 2017), CINAHL (1980 to 24 May 2017), the Australian New Zealand Clinical Trials Registry (18 May 2017), ClinicalTrials.gov (18 May 2017), the ISRCTN Register (18 May 2017), the WHO International Clinical Trials Registry Platform (ICTRP) (18 May 2017), and reference lists of retrieved studies. Randomised controlled trials (including quasi randomised and cluster trials) comparing relaxation methods with standard care, no treatment, other non-pharmacological forms of pain management in labour or placebo. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We attempted to contact study authors for additional information. We assessed evidence quality with GRADE methodology. This review update includes 19 studies (2519 women), 15 of which (1731 women) contribute data. Interventions examined included relaxation, yoga, music and mindfulness. Approximately half of the studies had a low risk of bias for random sequence generation and attrition bias. The majority of studies had a high risk of bias for performance and detection bias, and unclear risk of bias for, allocation concealment, reporting bias and other bias. We assessed the evidence from these studies as ranging from low to very low quality, and therefore the effects below should be interpreted with caution.RelaxationWe found that relaxation compared to usual care provided lowered the intensity of pain (measured on a scale of 0 to 10 with low scores indicating less pain) during the latent phase of labour (mean difference (MD) -1.25, 95% confidence interval (CI) -1.97 to -0.53, one trial, 40 women). Four trials reported pain intensity in the active phase; there was high heterogeneity between trials and very low-quality evidence suggested that there was no strong evidence that the effects were any different between groups for this outcome (MD -1.08, 95% CI -2.57 to 0.41, four trials, 271 women, random-effects analysis). Very low-quality evidence showed that women receiving relaxation reported greater satisfaction with pain relief during labour (risk ratio (RR) 8.00, 95% CI 1.10 to 58.19, one trial, 40 women), and showed no clear benefit for satisfaction with childbirth experience (assessed using different scales) (standard mean difference (SMD) -0.03, 95% CI -0.37 to 0.31, three trials, 1176 women). For safety outcomes there was very low-quality evidence of no clear reduction in assisted vaginal birth (average RR 0.61, 95% CI 0.20 to 1.84, four trials, 1122 women) or in caesarean section rates (average RR 0.73, 95% CI 0.26 to 2.01, four trials, 1122 women). Sense of control in labour, and breastfeeding were not reported under this comparison.YogaWhen comparing yoga to control interventions there was low-quality evidence that yoga lowered pain intensity (measured on a scale of 0 to 10) with low scores indicating less pain) (MD -6.12, 95% CI -11.77 to -0.47, one trial, 66 women), greater satisfaction with pain relief (MD 7.88, 95% CI 1.51 to 14.25, one trial, 66 women) and greater satisfaction with childbirth experience (MD 6.34, 95% CI 0.26 to 12.42 one trial, 66 women (assessed using the Maternal Comfort Scale with higher score indicating greater comfort). Sense of control in labour, breastfeeding, assisted vaginal birth, and caesarean section were not reported under this comparison.MusicWhen comparing music to control interventions there was evidence of lower pain intensity in the latent phase for women receiving music (measured on a scale of 0 to 10 with low scores indicating less pain) (MD -0.73, 95% CI -1.01 to -0.45, random-effects analysis, two trials, 192 women) and very low-quality evidence of no clear benefit in the active phase (MD -0.51, 95% CI -1.10 to 0.07, three trials, 217 women). Very low-quality evidence suggested no clear benefit in terms of reducing assisted vaginal birth (RR 0.41, 95% CI 0.08 to 2.05, one trial, 156 women) or caesarean section rate (RR 0.78, 95% CI 0.36 to 1.70, two trials, 216 women). Satisfaction with pain relief, sense of control in labour, satisfaction with childbirth experience, and breastfeeding were not reported under this comparison.Audio analgesiaOne trial evaluating audio analgesia versus control only reported one outcome and showed no evidence of benefit in satisfaction with pain relief.MindfulnessOne trial evaluating mindfulness versus usual care found an increase in sense of control for the mindfulness group (using the Childbirth Self-Efficacy Inventory) (MD 31.30, 95% CI 1.61 to 60.99, 26 women). There is no strong evidence that the effects were any different between groups for satisfaction in childbirth, or for caesarean section rate, need for assisted vaginal delivery or need for pharmacological pain relief. No other outcomes were reported in this trial. Relaxation, yoga and music may have a role with reducing pain, and increasing satisfaction with pain relief, although the quality of evidence varies between very low to low. There was insufficient evidence for the role of mindfulness and audio-analgesia. The majority of trials did not report on the safety of the interventions. Further randomised controlled trials of relaxation modalities for pain management in labour are needed. Trials should be adequately powered and include clinically relevant outcomes such as those described in this review.

Using Web 2.0 applications to promote health-related physical activity: findings from the WALK 2.0 randomised controlled trial

PubMed Central

Kolt, Gregory S; Rosenkranz, Richard R; Vandelanotte, Corneel; Caperchione, Cristina M; Maeder, Anthony J; Tague, Rhys; Savage, Trevor N; Van, Itallie Anetta; Mummery, W Kerry; Oldmeadow, Christopher; Duncan, Mitch J

2017-01-01

Background/Aim Web 2.0 internet technology has great potential in promoting physical activity. This trial investigated the effectiveness of a Web 2.0-based intervention on physical activity behaviour, and the impact on website usage and engagement. Methods 504 (328 women, 126 men) insufficiently active adult participants were randomly allocated to one of two web-based interventions or a paper-based Logbook group. The Web 1.0 group participated in the existing 10 000 Steps programme, while the Web 2.0 group participated in a Web 2.0-enabled physical activity intervention including user-to-user interaction through social networking capabilities. ActiGraph GT3X activity monitors were used to assess physical activity at four points across the intervention (0, 3, 12 and 18 months), and usage and engagement were assessed continuously through website usage statistics. Results Treatment groups differed significantly in trajectories of minutes/day of physical activity (p=0.0198), through a greater change at 3 months for Web 2.0 than Web 1.0 (7.3 min/day, 95% CI 2.4 to 12.3). In the Web 2.0 group, physical activity increased at 3 (mean change 6.8 min/day, 95% CI 3.9 to 9.6) and 12 months (3.8 min/day, 95% CI 0.5 to 7.0), but not 18 months. The Logbook group also increased physical activity at 3 (4.8 min/day, 95% CI 1.8 to 7.7) and 12 months (4.9 min/day, 95% CI 0.7 to 9.1), but not 18 months. The Web 1.0 group increased physical activity at 12 months only (4.9 min/day, 95% CI 0.5 to 9.3). The Web 2.0 group demonstrated higher levels of website engagement (p=0.3964). Conclusions In comparison to a Web 1.0 intervention, a more interactive Web 2.0 intervention, as well as the paper-based Logbook intervention, improved physical activity in the short term, but that effect reduced over time, despite higher levels of engagement of the Web 2.0 group. Trial registration number ACTRN12611000157976. PMID:28049624

Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation

PubMed Central

Webber, Emily S.; Mankin, David E.

2016-01-01

Abstract The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility. PMID:27822506

Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

PubMed

Webber, Emily S; Mankin, David E; Cromwell, Howard C

2016-01-01

The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats ( Rattus norvegicus ) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

Risk of bias assessment of randomised controlled trials in high-impact ophthalmology journals and general medical journals: a systematic review.

PubMed

Joksimovic, Lazar; Koucheki, Robert; Popovic, Marko; Ahmed, Yusuf; Schlenker, Matthew B; Ahmed, Iqbal Ike K

2017-10-01

Evidence-based treatments in ophthalmology are often based on the results of randomised controlled trials. Biased conclusions from randomised controlled trials may lead to inappropriate management recommendations. This systematic review investigates the prevalence of bias risk in randomised controlled trials published in high-impact ophthalmology journals and ophthalmology trials from general medical journals. Using Ovid MEDLINE, randomised controlled trials in the top 10 high-impact ophthalmology journals in 2015 were systematically identified and critically appraised for the prevalence of bias risk. Included randomised controlled trials were assessed in all domains of bias as defined by the Cochrane Collaboration. In addition, the prevalence of conflict of interest and industry sponsorship was investigated. A comparison with ophthalmology articles from high-impact general medical journals was performed. Of the 259 records that were screened from ophthalmology-specific journals, 119 trials met all inclusion criteria and were critically appraised. In total, 29.4% of domains had an unclear risk, 13.8% had a high risk and 56.8% had a low risk of bias. In comparison, ophthalmology articles from general medical journals had a lower prevalence of unclear risk (17.1%), higher prevalence of high risk (21.9%) and a higher prevalence of low risk domains (61.9%). Furthermore, 64.7% of critically appraised trials from ophthalmology-specific journals did not report any conflicts of interest, while 70.6% did not report an industry sponsor of their trial. In closing, it is essential that authors, peer reviewers and readers closely follow published risk of bias guidelines. © 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.

Wasted research when systematic reviews fail to provide a complete and up-to-date evidence synthesis: the example of lung cancer.

PubMed

Créquit, Perrine; Trinquart, Ludovic; Yavchitz, Amélie; Ravaud, Philippe

2016-01-20

Multiple treatments are frequently available for a given condition, and clinicians and patients need a comprehensive, up-to-date synthesis of evidence for all competing treatments. We aimed to quantify the waste of research related to the failure of systematic reviews to provide a complete and up-to-date evidence synthesis over time. We performed a series of systematic overviews and networks of randomized trials assessing the gap between evidence covered by systematic reviews and available trials of second-line treatments for advanced non-small cell lung cancer. We searched the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, MEDLINE, EMBASE, and other resources sequentially by year from 2009 to March 2, 2015. We sequentially compared the amount of evidence missing from systematic reviews to the randomized evidence available for inclusion each year. We constructed cumulative networks of randomized evidence over time and evaluated the proportion of trials, patients, treatments, and treatment comparisons not covered by systematic reviews on December 31 each year from 2009 to 2015. We identified 77 trials (28,636 patients) assessing 47 treatments with 54 comparisons and 29 systematic reviews (13 published after 2013). From 2009 to 2015, the evidence covered by existing systematic reviews was consistently incomplete: 45 % to 70 % of trials; 30 % to 58 % of patients; 40 % to 66 % of treatments; and 38 % to 71 % of comparisons were missing. In the cumulative networks of randomized evidence, 10 % to 17 % of treatment comparisons were partially covered by systematic reviews and 55 % to 85 % were partially or not covered. We illustrate how systematic reviews of a given condition provide a fragmented, out-of-date panorama of the evidence for all treatments. This waste of research might be reduced by the development of live cumulative network meta-analyses.

First year physical activity findings from turn up the HEAT (Healthy Eating and Activity Time) in summer day camps

PubMed Central

Brazendale, Keith; Chandler, Jessica L.; Turner-McGrievy, Gabrielle M.; Moore, Justin B.; Huberty, Jennifer L.; Ward, Dianne S.; Beets, Michael W.

2017-01-01

Background Summer day camps (SDCs) serve 14 million children yearly in the U.S. and aim to provide participating children with 60 minutes of moderate-to-vigorous physical activity (MVPA). This study evaluated an intervention designed to increase the percent of children meeting this MVPA guideline. Design Two-group, pre-post quasi-experimental. Setting/Participants Twenty SDCs serving 1,830 children aged 5–12 years were assigned to MVPA intervention (n = 10) or healthy eating attention control (n = 10). Intervention The STEPs (Strategies to Enhance Practice) intervention is a capacity-building approach grounded in the Theory of Expanded, Extended and Enhanced Opportunities. Camp leaders and staff receive training to expand (e.g., introduction of activity breaks/active field trips), extend (e.g., schedule minimum of 3 hours/day for PA opportunities), and enhance (e.g., maximize MVPA children accumulate during schedule activity) activity opportunities. Camps in the comparison condition received support for improving the types of foods/beverages served. Main outcome measures Percent of children accumulating the 60min/d MVPA guideline at baseline (summer 2015) and post-test (summer 2016) measured via wrist-accelerometry. Results Multilevel logistic regression conducted fall 2016 indicated boys and girls attending intervention SDCs were 2.04 (95CI = 1.10,3.78) and 3.84 (95CI = 2.02,7.33) times more likely to meet the 60min/d guideline compared to boys and girls attending control SDCs, respectively. This corresponded to increases of +10.6% (78–89%) and +12.6% (69–82%) in the percentage of boys and girls meeting the guideline in intervention SDCs, respectively. Boys in comparison SDCs increased by +1.6% (81–83%) and girls decreased by -5.5% (76–71%). Process data indicated intervention SDCs successfully extended and enhanced PA opportunities, but were unable to expand PA opportunities, compared to control SDCs. Conclusions Although substantial proportions of children met the MVPA guideline at baseline, no SDCs ensured all children met the guideline. This intervention demonstrated that, with support, SDCs can help all children in attendance to accumulate their daily recommended 60min MVPA. Trial registration ClinicalTrials.gov NCT02161809 PMID:28350830

Cost effectiveness of etanercept (Enbrel) in combination with methotrexate in the treatment of active rheumatoid arthritis based on the TEMPO trial.

PubMed

Kobelt, G; Lindgren, P; Singh, A; Klareskog, L

2005-08-01

To estimate the cost effectiveness of combination treatment with etanercept plus methotrexate in comparison with monotherapies in patients with active rheumatoid arthritis (RA) using a new model that incorporates both functional status and disease activity. Effectiveness data were based on a 2 year trial in 682 patients with active RA (TEMPO). Data on resource consumption and utility related to function and disease activity were obtained from a survey of 616 patients in Sweden. A Markov model was constructed with five states according to functional status (Health Assessment Questionnaire (HAQ)) subdivided into high and low disease activity. The cost for each quality adjusted life year (QALY) gained was estimated by Monte Carlo simulation. Disease activity had a highly significant effect on utilities, independently of HAQ. For resource consumption, only HAQ was a significant predictor, with the exception of sick leave. Compared with methotrexate alone, etanercept plus methotrexate over 2 years increased total costs by 14,221 euros and led to a QALY gain of 0.38. When treatment was continued for 10 years, incremental costs were 42,148 euros for a QALY gain of 0.91. The cost per QALY gained was 37,331 euros and 46,494 euros, respectively. The probability that the cost effectiveness ratio is below a threshold of 50,000 euros/QALY is 88%. Incorporating the influence of disease activity into this new model allows better assessment of the effects of anti-tumour necrosis factor treatment on patients' general wellbeing. In this analysis, the cost per QALY gained with combination treatment with etanercept plus methotrexate compared with methotrexate alone falls within the acceptable range.

2D and 3D similarity landscape analysis identifies PARP as a novel off-target for the drug Vatalanib.

PubMed

Gohlke, Bjoern-Oliver; Overkamp, Tim; Richter, Anja; Richter, Antje; Daniel, Peter T; Gillissen, Bernd; Preissner, Robert

2015-09-24

Searching for two-dimensional (2D) structural similarities is a useful tool to identify new active compounds in drug-discovery programs. However, as 2D similarity measures neglect important structural and functional features, similarity by 2D might be underestimated. In the present study, we used combined 2D and three-dimensional (3D) similarity comparisons to reveal possible new functions and/or side-effects of known bioactive compounds. We utilised more than 10,000 compounds from the SuperTarget database with known inhibition values for twelve different anti-cancer targets. We performed all-against-all comparisons resulting in 2D similarity landscapes. Among the regions with low 2D similarity scores are inhibitors of vascular endothelial growth factor receptor (VEGFR) and inhibitors of poly ADP-ribose polymerase (PARP). To demonstrate that 3D landscape comparison can identify similarities, which are untraceable in 2D similarity comparisons, we analysed this region in more detail. This 3D analysis showed the unexpected structural similarity between inhibitors of VEGFR and inhibitors of PARP. Among the VEGFR inhibitors that show similarities to PARP inhibitors was Vatalanib, an oral "multi-targeted" small molecule protein kinase inhibitor being studied in phase-III clinical trials in cancer therapy. An in silico docking simulation and an in vitro HT universal colorimetric PARP assay confirmed that the VEGFR inhibitor Vatalanib exhibits off-target activity as a PARP inhibitor, broadening its mode of action. In contrast to the 2D-similarity search, the 3D-similarity landscape comparison identifies new functions and side effects of the known VEGFR inhibitor Vatalanib.

Effects of internet-based pain coping skills training prior to home exercise for individuals with hip osteoarthritis (HOPE trial): a randomised controlled trial.

PubMed

Bennell, Kim L; Nelligan, Rachel K; Rini, Christine; Keefe, Francis J; Kasza, Jessica; French, Simon; Forbes, Andrew; Dobson, Fiona; Abbott, J Haxby; Dalwood, Andrew; Harris, Anthony; Vicenzino, Bill; Hodges, Paul W; Hinman, Rana S

2018-05-22

This assessor-, therapist- and participant-blinded randomised controlled trial evaluated the effects of an automated internet-based pain coping skills training (PCST) program prior to home exercise for people with clinically-diagnosed hip osteoarthritis (OA). 144 people were randomised to either the PCST group or the comparator group. In the first 8 weeks, the PCST group received online education and PCST while the comparison group received online education only. From weeks 8-24, both groups visited a physiotherapist 5 times for home exercise prescription. Assessments were performed at baseline, 8, 24 and 52 weeks. Primary outcomes were hip pain on walking (11-point numerical rating scale) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) at 24 weeks. Secondary outcomes were other measures of pain, quality-of-life, global change, self-efficacy, pain coping, pain catastrophizing, depression, anxiety, stress, physical activity and adverse events. Primary outcomes were completed by 137 (95%), 131 (91%) and 127 (88%) participants at 8, 24 and 52 weeks, respectively. There were no significant between-group differences in primary outcomes at week 24 (change in: walking pain (mean difference 0.5 units; 95%CI, -0.3 to 1.3) and function (-0.9 units; 95%CI, -4.8 to 2.9)), with both groups showing clinically-relevant improvements. At week 8, the PCST group had greater improvements in function, pain coping and global improvement than comparison. Greater pain coping improvements persisted at 24 and 52 weeks. In summary, online PCST immediately improved pain coping and function but did not confer additional benefits to a subsequent exercise program, despite sustained pain coping improvements.

A Comparison of Mixed-Method Cooling Interventions on Preloaded Running Performance in the Heat.

PubMed

Stevens, Christopher J; Bennett, Kyle J M; Sculley, Dean V; Callister, Robin; Taylor, Lee; Dascombe, Ben J

2017-03-01

Stevens, CJ, Bennett, KJM, Sculley, DV, Callister, R, Taylor, L, and Dascombe, BJ. A comparison of mixed-method cooling interventions on preloaded running performance in the heat. J Strength Cond Res 31(3): 620-629, 2017-The purpose of this investigation was to assess the effect of combining practical methods to cool the body on endurance running performance and physiology in the heat. Eleven trained male runners completed 4 randomized, preloaded running time trials (20 minutes at 70% V[Combining Dot Above]O2max and a 3 km time trial) on a nonmotorized treadmill in the heat (33° C). Trials consisted of precooling by combined cold-water immersion and ice slurry ingestion (PRE), midcooling by combined facial water spray and menthol mouth rinse (MID), a combination of all methods (ALL), and control (CON). Performance time was significantly faster in MID (13.7 ± 1.2 minutes; p < 0.01) and ALL (13.7 ± 1.4 minutes; p = 0.04) but not PRE (13.9 ± 1.4 minutes; p = 0.24) when compared with CON (14.2 ± 1.2 minutes). Precooling significantly reduced rectal temperature (initially by 0.5 ± 0.2° C), mean skin temperature, heart rate and sweat rate, and increased iEMG activity, whereas midcooling significantly increased expired air volume and respiratory exchange ratio compared with control. Significant decreases in forehead temperature, thermal sensation, and postexercise blood prolactin concentration were observed in all conditions compared with control. Performance was improved with midcooling, whereas precooling had little or no influence. Midcooling may have improved performance through an attenuated inhibitory psychophysiological and endocrine response to the heat.

Together We STRIDE: A quasi-experimental trial testing the effectiveness of a multi-level obesity intervention for Hispanic children in rural communities.

PubMed

Ko, Linda K; Rillamas-Sun, Eileen; Bishop, Sonia; Cisneros, Oralia; Holte, Sarah; Thompson, Beti

2018-04-01

Hispanic children are disproportionally overweight and obese compared to their non-Hispanic white counterparts in the US. Community-wide, multi-level interventions have been successful to promote healthier nutrition, increased physical activity (PA), and weight loss. Using community-based participatory approach (CBPR) that engages community members in rural Hispanic communities is a promising way to promote behavior change, and ultimately weight loss among Hispanic children. Led by a community-academic partnership, the Together We STRIDE (Strategizing Together Relevant Interventions for Diet and Exercise) aims to test the effectiveness of a community-wide, multi-level intervention to promote healthier diets, increased PA, and weight loss among Hispanic children. The Together We STRIDE is a parallel quasi-experimental trial with a goal of recruiting 900 children aged 8-12 years nested within two communities (one intervention and one comparison). Children will be recruited from their respective elementary schools. Components of the 2-year multi-level intervention include comic books (individual-level), multi-generational nutrition and PA classes (family-level), teacher-led PA breaks and media literacy education (school-level), family nights, a farmer's market and a community PA event (known as ciclovia) at the community-level. Children from the comparison community will receive two newsletters. Height and weight measures will be collected from children in both communities at three time points (baseline, 6-months, and 18-months). The Together We STRIDE study aims to promote healthier diet and increased PA to produce healthy weight among Hispanic children. The use of CBPR approach and the engagement of the community will springboard strategies for intervention' sustainability. Clinical Trials Registration Number: NCT02982759 Retrospectively registered. Copyright © 2018 Elsevier Inc. All rights reserved.

Modelling Comparative Efficacy of Drugs with Different Survival Profiles: Ipilimumab, Vemurafenib and Dacarbazine in Advanced Melanoma.

PubMed

Lee, D; Porter, J; Hertel, N; Hatswell, A J; Briggs, A

2016-08-01

In the absence of head-to-head data, a common method for modelling comparative survival for cost-effectiveness analysis is estimating hazard ratios from trial publications. This assumes that the hazards of mortality are proportional between treatments and that outcomes are not polluted by subsequent therapy use. Newer techniques that compare treatments where the proportional hazards assumption is violated and adjust for use of subsequent therapies often require patient-level data, which are rarely available for all treatments. The objective of this study was to provide a comparison of overall survival data for ipilimumab, vemurafenib and dacarbazine using data from three trials lacking a common comparator arm and confounded by the use of subsequent treatment. We compared three estimated overall survival curves for vemurafenib and the difference compared to ipilimumab and dacarbazine. We performed a naïve comparison and adjusted it for heterogeneity between the ipilimumab and vemurafenib trials, including differences in prognostic characteristics and subsequent therapy using a published hazard function for the impact of prognostic characteristics in melanoma and trial data on the impact of second-line use of ipilimumab. The mean incremental life-years gained for patients receiving ipilimumab compared with vemurafenib were 0.34 (95 % confidence interval [CI] -0.24 to 0.84) using the naïve comparison and 0.51 (95 % CI -0.08 to 0.99) using the covariate-adjusted survival curve. The analyses estimated the comparative efficacy of ipilimumab and vemurafenib in the absence of head-to-head patient-level data for all trials and proportional hazards in overall survival.

Botulinum toxins for the prevention of migraine in adults.

PubMed

Herd, Clare P; Tomlinson, Claire L; Rick, Caroline; Scotton, W J; Edwards, Julie; Ives, Natalie; Clarke, Carl E; Sinclair, Alexandra

2018-06-25

Migraine occurs in around 15% of adults and is ranked as the seventh most disabling disease amongst all diseases globally. Despite the available treatments many people suffer prolonged and frequent attacks which have a major impact on their quality of life. Chronic migraine is defined as 15 or more days of headache per month, at least eight of those days being migraine. People with episodic migraine have fewer than 15 headache days per month. Botulinum toxin type A has been licensed in some countries for chronic migraine treatment, due to the results of just two trials. To assess the effects of botulinum toxins versus placebo or active treatment for the prevention or reduction in frequency of chronic or episodic migraine in adults. We searched CENTRAL, MEDLINE & MEDLINE in Process, Embase, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry (to December 2017). We examined reference lists and carried out citation searches on key publications. We sent correspondence to major manufacturers of botulinum toxin. Randomised, double-blind, controlled trials of botulinum toxin (any sero-type) injections into the head and neck for prophylaxis of chronic or episodic migraine in adults. Eligible comparators were placebo, alternative prophylactic agent or different dose of botulinum toxin. Two review authors independently selected trials and extracted data. For continuous outcomes we used mean change data when available. For dichotomous data we calculated risk ratios (RRs). We used data from the 12-week post-treatment follow-up time point. We assessed the evidence using GRADE and created two 'Summary of findings' tables. Description of trialsWe found 90 articles describing 28 trials (4190 participants), which were eligible for inclusion. The longest treatment duration was three rounds of injections with three months between treatments, so we could not analyse long-term effects. For the primary analyses, we pooled data from both chronic and episodic participant populations. Where possible, we also separated data into chronic migraine, episodic migraine and 'mixed group' classification subgroups. Most trials (21 out of 28) were small (fewer than 50 participants per trial arm). The risk of bias for included trials was low or unclear across most domains, with some trials reporting a high risk of bias for incomplete outcome data and selective outcome reporting.Botulinum toxin versus placeboTwenty-three trials compared botulinum toxin with placebo. Botulinum toxin may reduce the number of migraine days per month in the chronic migraine population by 3.1 days (95% confidence interval (CI) -4.7 to -1.4, 4 trials, 1497 participants, low-quality evidence). This was reduced to -2 days (95% CI -2.8 to -1.1, 2 trials, 1384 participants; moderate-quality evidence) when we removed small trials.A single trial of people with episodic migraine (N = 418) showed no difference between groups for this outcome measure (P = 0.49).In the chronic migraine population, botulinum toxin reduces the number of headache days per month by 1.9 days (95% CI -2.7 to -1.0, 2 trials, 1384 participants, high-quality evidence). We did not find evidence of a difference in the number of migraine attacks for both chronic and episodic migraine participants (6 trials, N = 2004, P = 0.30, low-quality evidence). For the population of both chronic and episodic migraine participants a reduction in severity of migraine rated during clinical visits, on a 10 cm visual analogue scale (VAS) of 3.3 cm (95% CI -4.2 to -2.5, very low-quality evidence) in favour of botulinum toxin treatment came from four small trials (N = 209); better reporting of this outcome measure from the additional eight trials that recorded it may have improved our confidence in the pooled estimate. Global assessment and quality-of-life measures were poorly reported and it was not possible to carry out statistical analysis of these outcome measures. Analysis of adverse events showed an increase in the risk ratio with treatment with botulinum toxin over placebo 30% (RR 1.28, 95% CI 1.12 to 1.47, moderate-quality evidence). For every 100 participants 60 experienced an adverse event in the botulinum toxin group compared with 47 in the placebo group.Botulinum toxin versus other prophylactic agentThree trials studied comparisons with alternative oral prophylactic medications. Meta-analyses were not possible for number of migraine days, number of headache days or number of migraine attacks due to insufficient data, but individually trials reported no differences between groups for a variety of efficacy measures in the population of both chronic and episodic migraine participants. The global impression of disease measured using Migraine Disability Assessment (MIDAS) scores were reported from two trials that showed no difference between groups. Compared with oral treatments, botulinum toxin showed no between-group difference in the risk of adverse events (2 trials, N = 114, very low-quality evidence). The relative risk reduction (RRR) for withdrawing from botulinum toxin due to adverse events compared with the alternative prophylactic agent was 72% (P = 0.02, 2 trials, N = 119).Dosing trialsThere were insufficient data available for the comparison of different doses.Quality of the evidenceThe quality of the evidence assessed using GRADE methods was varied but mostly very low; the quality of the evidence for the placebo and active control comparisons was low and very low, respectively for the primary outcome measure. Small trial size, high risk of bias and unexplained heterogeneity were common reasons for downgrading the quality of the evidence. In chronic migraine, botulinum toxin type A may reduce the number of migraine days per month by 2 days compared with placebo treatment. Non-serious adverse events were probably experienced by 60/100 participants in the treated group compared with 47/100 in the placebo group. For people with episodic migraine, we remain uncertain whether or not this treatment is effective because the quality of this limited evidence is very low. Better reporting of outcome measures in published trials would provide a more complete evidence base on which to draw conclusions.

Effects of a caregiver-inclusive assistive technology intervention: a randomized controlled trial.

PubMed

Ben Mortenson, W; Demers, Louise; Fuhrer, Marcus J; Jutai, Jeffrey W; Bilkey, Jessica; Plante, Michelle; DeRuyter, Frank

2018-04-18

The principal aim of this study was to investigate whether a caregiver-inclusive assistive technology intervention improved older care recipients' functional autonomy and decreased the perceived burden of their family caregivers compared to customary care. The study was a single-blind, mixed-methods, randomized controlled trial with baseline data collection and follow-ups at 6-, 22-, and 58-weeks after baseline evaluation, which was prospectively registered ( ClinicalTrials.gov Identifier: NCT01640470. Registered 11/21/2011). Dyads comprising a care recipient and family caregiver were randomly assigned to either a caregiver-inclusive experimental group (N = 44) or a customary-care comparison group (N = 46). Eligible care recipients were aged ≥55 years and had one or more limitations with mobility or daily activities, and family caregivers provided at least four hours per week of assistance. Outcome measures were administered to both groups at baseline and at the three follow-up time points. The data collectors were blinded regarding participants' intervention group. The primary outcome measures were the Functional Autonomy Measurement System to assess care recipients' functional performance, and the Caregiver Assistive Technology Outcome Measure to assess caregivers' burden. Qualitative interviews examined participants' perceptions of the caregiver-inclusive and customary care interventions. The experimental intervention addressed significantly more dyad-identified problematic activities, but caregiver involvement was evident in both groups and outcomes were not significantly different over time. In both groups, care recipients' functional autonomy declined significantly (P < .01), and caregivers' activity-specific and overall burden decreased significantly (P < .01). Given the unintended congruence between the caregiver-inclusive and customary care interventions, the overall findings lend support for the provision of assistive technology to reduce caregiver burden.

EDTA Chelation Therapy Alone and in Combination with Oral High-Dose Multivitamins and Minerals for Coronary Disease: The Factorial Group Results of the Trial to Assess Chelation Therapy

PubMed Central

Lamas, Gervasio A.; Boineau, Robin; Goertz, Christine; Mark, Daniel B.; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L.; Chappell, L. Terry; Lindblad, Lauren; Lewis, Eldrin F.; Drisko, Jeanne; Lee, Kerry L.

2014-01-01

Background Disodium ethylene diamine tetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. Objective This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes. Methods Double-blind placebo-controlled 2 × 2 factorial multicenter randomized trial of 1708 post-MI patients ≥ 50 years and creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitaminmultimineral mixture or placebo. Primary endpoint was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina. Results Median age was 65 years, 18% female, 94% Caucasian, 37% diabetic, 83% prior coronary revascularization, and 73% on statins. Five-year Kaplan-Meier estimates for the primary endpoint in the chelation + high-dose vitamin group was 31.9%, in the chelation + placebo vitamin group 33.7%, in the placebo infusion + active vitamin group 36.6%, and in the placebo infusions + placebo vitamin group 40.2 %. The reduction in primary endpoint by double active treatment compared with double placebo was significant (HR 0.74, 95% CI (0.57,0.95); p=0.016). In patients with diabetes, the primary endpoint reduction of double active compared with double placebo was more pronounced (HR 0.49, 95% CI (0.33,0.75), p<0.001). Conclusions In stable post- MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance. PMID:24952858

The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review.

PubMed

Fritoli, Aretuza; Gonçalves, Cristiane; Faveri, Marcelo; Figueiredo, Luciene Cristina; Pérez-Chaparro, Paula Juliana; Fermiano, Daiane; Feres, Magda

2015-01-01

The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT) that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP) at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm) than subjects taking antibiotics after healing (p<0.05). This comparison was conducted 2 months after antibiotic intake, at the healing phase. To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods.

Two-Year Outcomes of the Enabling Mothers to Prevent Pediatric Obesity Through Web-Based Education and Reciprocal Determinism (EMPOWER) Randomized Control Trial.

PubMed

Knowlden, Adam P; Conrad, Eric

2018-04-01

Childhood overweight and obesity is a public health epidemic with far-reaching medical, economic, and quality of life consequences. Brief, web-based interventions have received increased attention for their potential to combat childhood obesity. The purpose of our study was to evaluate a web-based, maternal-facilitated childhood obesity prevention intervention dubbed Enabling Mothers to Prevent Pediatric Obesity Through Web-Based Education and Reciprocal Determinism (EMPOWER), for its capacity to elicit sustained effects at the 2-year postintervention follow-up mark. Two interventions were evaluated using a randomized controlled trial design. The experimental, EMPOWER arm received a social cognitive theory intervention ( n = 29) designed to improve four maternal-facilitated behaviors in children (fruit and vegetable consumption, physical activity, sugar-free beverage intake, screen time). The active control arm received a knowledge-based intervention dubbed Healthy Lifestyles ( n = 28), which also targeted the same four behaviors. We identified a significant group-by-time interaction of small effect size for child fruit and vegetable consumption ( p = .033; Cohen's f = 0.139) in the EMPOWER group. The construct of maternal-facilitated environment was positively associated to improvements in child fruit and vegetable behavior. We also found significant main effects for child physical activity ( p = .024; Cohen's f = 0.124); sugar-free beverage intake ( p < .001; Cohen's f = 0.321); and screen time ( p < .001; Cohen's f = 0.303), suggesting both groups improved in these behaviors over time. The EMPOWER arm of the trial resulted in an overall increase of 1.680 daily cups of fruits and vegetables consumed by children, relative to the comparison group ( p < .001, 95% confidence interval = [1.113, 2.248]). Web-based maternal-facilitated interventions can induce sustained effects on child behaviors.

Validation of the DIFFAL, HPAC and HotSpot Dispersion Models Using the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials Witness Plate Deposition Dataset.

PubMed

Purves, Murray; Parkes, David

2016-05-01

Three atmospheric dispersion models--DIFFAL, HPAC, and HotSpot--of differing complexities have been validated against the witness plate deposition dataset taken during the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials. The small-scale nature of these trials in comparison to many other historical radiological dispersion trials provides a unique opportunity to evaluate the near-field performance of the models considered. This paper performs validation of these models using two graphical methods of comparison: deposition contour plots and hotline profile graphs. All of the models tested are assessed to perform well, especially considering that previous model developments and validations have been focused on larger-scale scenarios. Of the models, HPAC generally produced the most accurate results, especially at locations within ∼100 m of GZ. Features present within the observed data, such as hot spots, were not well modeled by any of the codes considered. Additionally, it was found that an increase in the complexity of the meteorological data input to the models did not necessarily lead to an improvement in model accuracy; this is potentially due to the small-scale nature of the trials.

Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients (CAVIAR): study protocol for a randomised controlled trial.

PubMed

Wilcox, Joanne; Waite, Chantelle; Tomlinson, Lyndsey; Driscoll, Joanne; Karim, Asra; Day, Edward; Sharif, Adnan

2016-08-22

Lifestyle modification is widely recommended to kidney allograft recipients post transplantation due to the cardiometabolic risks associated with immunosuppression including new-onset diabetes, weight gain and cardiovascular events. However, we have no actual evidence that undertaking lifestyle modification protects from any adverse outcomes post transplantation. The aim of this study is to compare whether a more proactive versus passive interventional approach to modify lifestyle is associated with superior outcomes post kidney transplantation. We designed this prospective, single-centre, open-label, randomised controlled study to compare the efficacy of active versus passive lifestyle intervention for kidney allograft recipients early post transplantation. A total of 130 eligible patients, who are stable, nondiabetic and between 3 and 24 months post kidney transplantation, will be recruited. Randomisation is being undertaken by random block permutations into passive (n = 65, leaflet guidance only) versus active lifestyle modification (n = 65, supervised intervention) over a 6-month period. Supervised intervention is being facilitated by two dietitians during the 6-month intervention period to provide continuous lifestyle intervention guidance, support and encouragement. Both dietitians are accredited with behavioural intervention skills and will utilise motivational aids to support study recruits randomised to active intervention. The primary outcome is change in abnormal glucose metabolism parameters after 6 months of comparing active versus passive lifestyle intervention. Secondary outcomes include changes in a wide array of cardiometabolic parameters, kidney allograft function and patient-reported outcome measures. Long-term tracking of patients via data linkage to electronic patient records and national registries will facilitate long-term comparison of outcomes after active versus passive lifestyle intervention beyond the 6-month intervention period. This is the first randomised controlled study to investigate the benefits of active versus passive lifestyle intervention in kidney allograft recipients for the prevention of abnormal cardiometabolic outcomes. In addition, this is the first example of utilising behaviour therapy intervention post kidney transplantation to achieve clinically beneficial outcomes, which has potential implications on many spheres of post-transplant care. This study was registered with the Clinical Trials Registry on 27 August 2014 (ClinicalTrials.org Identifier: NCT02233491 ).

Topical treatments for chronic plaque psoriasis.

PubMed

Mason, Anne R; Mason, James; Cork, Michael; Dooley, Gordon; Hancock, Helen

2013-03-28

Chronic plaque psoriasis is the most common type of psoriasis, and it is characterised by redness, thickness, and scaling. First-line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid, and topical retinoids. To compare the effectiveness, tolerability, and safety of topical treatments for chronic plaque psoriasis, relative to placebo, and to similarly compare vitamin D analogues (used alone or in combination) with other topical treatments. We updated our searches of the following databases to February 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2011, Issue 2), MEDLINE (from 1948), EMBASE (from 1980), Science Citation Index (from 2008), Conference Proceedings Citation Index - Science (from 2008), BIOSIS (from 1993), Dissertation Abstracts via DialogClassic (all publication years), and Inside Conferences (all publication years).We identified ongoing and unpublished studies from the UK Clinical Research Network Study Portfolio and the metaRegister of Controlled Trials. We checked the bibliographies of published studies and reviews for further references to relevant trials, and we contacted trialists and companies for information about newly published studies.A separate search for adverse effects was undertaken in February 2011 using MEDLINE and EMBASE (from 2005).Final update searches for both RCTs and adverse effects were undertaken in August 2012. Although it has not been possible to incorporate RCTs and adverse effects studies identified through these final searches within this review, we will incorporate these into the next update. Randomised trials comparing active topical treatments against placebo or against vitamin D analogues (used alone or in combination) in people with chronic plaque psoriasis. One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted trialists and companies for missing data. We also extracted data on withdrawals and on local and systemic adverse events. We defined long-term trials as those with a duration of at least 24 weeks. This update added 48 trials and provided evidence on 7 new active treatments. In total, the review included 177 randomised controlled trials, with 34,808 participants, including 26 trials of scalp psoriasis and 6 trials of inverse psoriasis, facial psoriasis, or both. The number of included studies counted by Review Manager (RevMan) is higher than these figures (190) because we entered each study reporting a placebo and an active comparison into the 'Characteristics of included studies' table as 2 studies.When used on the body, most vitamin D analogues were significantly more effective than placebo, with the standardised mean difference (SMD) ranging from -0.67 (95% CI -1.04 to -0.30; 1 study, 119 participants) for twice-daily becocalcidiol to SMD -1.66 (95% CI -2.66 to -0.67; 1 study, 11 participants) for once-daily paricalcitol. On a 6-point global improvement scale, these effects translate into 0.8 and 1.9 points, respectively. Most corticosteroids also performed better than placebo; potent corticosteroids (SMD -0.89; 95% CI -1.06 to -0.72; I² statistic = 65.1%; 14 studies, 2011 participants) had smaller benefits than very potent corticosteroids (SMD -1.56; 95% CI -1.87 to -1.26); I² statistic = 81.7%; 10 studies, 1264 participants). On a 6-point improvement scale, these benefits equate to 1.0 and 1.8 points, respectively. Dithranol, combined treatment with vitamin D/corticosteroid, and tazarotene all performed significantly better than placebo.Head-to-head comparisons of vitamin D for psoriasis of the body against potent or very potent corticosteroids had mixed findings. For both body and scalp psoriasis, combined treatment with vitamin D and corticosteroid performed significantly better than vitamin D alone or corticosteroid alone. Vitamin D generally performed better than coal tar, but findings relative to dithranol were mixed. When applied to psoriasis of the scalp, vitamin D was significantly less effective than both potent corticosteroids and very potent corticosteroids. Indirect evidence from placebo-controlled trials supported these findings.For both body and scalp psoriasis, potent corticosteroids were less likely than vitamin D to cause local adverse events, such as burning or irritation. Combined treatment with vitamin D/corticosteroid on either the body or the scalp was tolerated as well as potent corticosteroids, and significantly better than vitamin D alone. Only 25 trials assessed clinical cutaneous dermal atrophy; few cases were detected, but trials reported insufficient information to determine whether assessment methods were robust. Clinical measurements of dermal atrophy are insensitive and detect only the most severe cases. No comparison of topical agents found a significant difference in systemic adverse effects. Corticosteroids perform at least as well as vitamin D analogues, and they are associated with a lower incidence of local adverse events. However, for people with chronic plaque psoriasis receiving long-term treatment with corticosteroids, there remains a lack of evidence about the risk of skin dermal atrophy. Further research is required to inform long-term maintenance treatment and provide appropriate safety data.

Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy.

PubMed

Smith, Lesley A; Azariah, Fredric; Lavender, Verna T C; Stoner, Nicola S; Bettiol, Silvana

2015-11-12

Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use. To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer. We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication. We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy. At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI). We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I(2) = 0% in both analyses).People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I(2) = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I(2) = 0%).People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence). Comparison with other anti-emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I(2) = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I(2) = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I(2) = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I(2) = 0%).People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I(2) = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I(2) = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I(2) = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I(2) = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I(2) = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I(2) = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I(2) = 51%; low quality evidence).In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.Two trials with 141 participants compared an anti-emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events. Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results. Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.

Effect of a 6-Week Active Play Intervention on Fundamental Movement Skill Competence of Preschool Children.

PubMed

Foulkes, J D; Knowles, Z; Fairclough, S J; Stratton, G; O'Dwyer, M; Ridgers, N D; Foweather, L

2017-04-01

This study examined the effectiveness of an active play intervention on fundamental movement skills of 3- to 5-year-old children from deprived communities. In a cluster randomized controlled trial design, six preschools received a resource pack and a 6-week local authority program involving staff training with help implementing 60-minute weekly sessions and postprogram support. Six comparison preschools received a resource pack only. Twelve skills were assessed at baseline, postintervention, and at a 6-month follow-up using the Children's Activity and Movement in Preschool Study Motor Skills Protocol. One hundred and sixty-two children (Mean age = 4.64 ± 0.58 years; 53.1% boys) were included in the final analyses. There were no significant differences between groups for total fundamental movement skill, object-control skill or locomotor skill scores, indicating a need for program modification to facilitate greater skill improvements.

Granular activated carbon for removal of organic matter and turbidity from secondary wastewater.

PubMed

Hatt, J W; Germain, E; Judd, S J

2013-01-01

A range of commercial granular activated carbon (GAC) media have been assessed as pretreatment technologies for a downstream microfiltration (MF) process. Media were assessed on the basis of reduction in both organic matter and turbidity, since these are known to cause fouling in MF membranes. Isotherm adsorption analysis through jar testing with supplementary column trials revealed a wide variation between the different adsorbent materials with regard to organics removal and adsorption kinetics. Comparison with previous work using powdered activated carbon (PAC) revealed that for organic removal above 60% the use of GAC media incurs a significantly lower carbon usage rate than PAC. All GACs tested achieved a minimum of 80% turbidity removal. This combination of turbidity and organic removal suggests that GAC would be expected to provide a significant reduction in fouling of a downstream MF process with improved product water quality.

Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease.

PubMed

Egan, Michael F; Kost, James; Tariot, Pierre N; Aisen, Paul S; Cummings, Jeffrey L; Vellas, Bruno; Sur, Cyrille; Mukai, Yuki; Voss, Tiffini; Furtek, Christine; Mahoney, Erin; Harper Mozley, Lyn; Vandenberghe, Rik; Mo, Yi; Michelson, David

2018-05-03

Alzheimer's disease is characterized by the deposition of amyloid-beta (Aβ) plaques in the brain. Aβ is produced from the sequential cleavage of amyloid precursor protein by β-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) followed by γ-secretase. Verubecestat is an oral BACE-1 inhibitor that reduces the Aβ level in the cerebrospinal fluid of patients with Alzheimer's disease. We conducted a randomized, double-blind, placebo-controlled, 78-week trial to evaluate verubecestat at doses of 12 mg and 40 mg per day, as compared with placebo, in patients who had a clinical diagnosis of mild-to-moderate Alzheimer's disease. The coprimary outcomes were the change from baseline to week 78 in the score on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog; scores range from 0 to 70, with higher scores indicating worse dementia) and in the score on the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL; scores range from 0 to 78, with lower scores indicating worse function). A total of 1958 patients underwent randomization; 653 were randomly assigned to receive verubecestat at a dose of 12 mg per day (the 12-mg group), 652 to receive verubecestat at a dose of 40 mg per day (the 40-mg group), and 653 to receive matching placebo. The trial was terminated early for futility 50 months after onset, which was within 5 months before its scheduled completion, and after enrollment of the planned 1958 patients was complete. The estimated mean change from baseline to week 78 in the ADAS-cog score was 7.9 in the 12-mg group, 8.0 in the 40-mg group, and 7.7 in the placebo group (P=0.63 for the comparison between the 12-mg group and the placebo group and P=0.46 for the comparison between the 40-mg group and the placebo group). The estimated mean change from baseline to week 78 in the ADCS-ADL score was -8.4 in the 12-mg group, -8.2 in the 40-mg group, and -8.9 in the placebo group (P=0.49 for the comparison between the 12-mg group and the placebo group and P=0.32 for the comparison between the 40-mg group and the placebo group). Adverse events, including rash, falls and injuries, sleep disturbance, suicidal ideation, weight loss, and hair-color change, were more common in the verubecestat groups than in the placebo group. Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. (Funded by Merck; ClinicalTrials.gov number, NCT01739348 .).

Comparison of sEMG processing methods during whole-body vibration exercise.

PubMed

Lienhard, Karin; Cabasson, Aline; Meste, Olivier; Colson, Serge S

2015-12-01

The objective was to investigate the influence of surface electromyography (sEMG) processing methods on the quantification of muscle activity during whole-body vibration (WBV) exercises. sEMG activity was recorded while the participants performed squats on the platform with and without WBV. The spikes observed in the sEMG spectrum at the vibration frequency and its harmonics were deleted using state-of-the-art methods, i.e. (1) a band-stop filter, (2) a band-pass filter, and (3) spectral linear interpolation. The same filtering methods were applied on the sEMG during the no-vibration trial. The linear interpolation method showed the highest intraclass correlation coefficients (no vibration: 0.999, WBV: 0.757-0.979) with the comparison measure (unfiltered sEMG during the no-vibration trial), followed by the band-stop filter (no vibration: 0.929-0.975, WBV: 0.661-0.938). While both methods introduced a systematic bias (P < 0.001), the error increased with increasing mean values to a higher degree for the band-stop filter. After adjusting the sEMG(RMS) during WBV for the bias, the performance of the interpolation method and the band-stop filter was comparable. The band-pass filter was in poor agreement with the other methods (ICC: 0.207-0.697), unless the sEMG(RMS) was corrected for the bias (ICC ⩾ 0.931, %LOA ⩽ 32.3). In conclusion, spectral linear interpolation or a band-stop filter centered at the vibration frequency and its multiple harmonics should be applied to delete the artifacts in the sEMG signals during WBV. With the use of a band-stop filter it is recommended to correct the sEMG(RMS) for the bias as this procedure improved its performance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Psychotherapy for bulimia nervosa on symptoms of depression: A meta-analysis of randomized controlled trials.

PubMed

Linardon, Jake; Wade, Tracey; de la Piedad Garcia, Xochitl; Brennan, Leah

2017-10-01

Depressive symptoms are an important risk factor and consequence of binge eating and purging behavior in bulimia nervosa (BN). Although psychotherapy is effective in reducing symptoms of BN in the short- and long-term, it is unclear whether psychotherapy for BN is also effective in reducing depressive symptoms. This meta-analysis examined the efficacy of psychotherapy for BN on depressive symptoms in the short- and long-term. Randomized controlled trials (RCTs) on BN that assessed depressive symptoms as an outcome were identified. Twenty-six RCTs were included. Psychotherapy was more efficacious at reducing symptoms of depression at post-treatment (g = 0.47) than wait-lists. This effect was strongest when studies delivered therapist-led, rather than guided self-help, treatment. No significant differences were observed between psychotherapy and antidepressants. There was no significant post-treatment difference between CBT and other active psychological comparisons at reducing symptoms of depression. However, when only therapist-led CBT was analyzed, therapist-led CBT was significantly more efficacious (g = 0.25) than active comparisons at reducing depressive symptoms. The magnitude of the improvement in depressive symptoms was predicted by the magnitude of the improvement in BN symptoms. These findings suggest that psychotherapy is effective for reducing depressive symptoms in BN in the short-term. Whether these effects are sustained in the long-term is yet to be determined, as too few studies conducted follow-up assessments. Moreover, findings demonstrate that, in addition to being the front-running treatment for BN symptoms, CBT might also be the most effective psychotherapy for improving the symptoms of depression that commonly co-occur in BN. © 2017 Wiley Periodicals, Inc.

Effects of aqueous extracts of dried calyx of sour tea (Hibiscus sabdariffa L.) on polygenic dyslipidemia: A randomized clinical trial.

PubMed

Hajifaraji, Majid; Matlabi, Mohammad; Ahmadzadeh-Sani, Farihe; Mehrabi, Yadollah; Rezaee, Mohammad Salem; Hajimehdipour, Homa; Hasanzadeh, Abbas; Roghani, Katayoun

2018-01-01

Dyslipidemia has been considered as a major risk factor for coronary heart disease. Alternative medicine has a significant role in treatment of dyslipidemia. There are controversial findings regarding the effects of sour tea on dyslipidemia. The aim of this study was to evaluate the impact of aqueous extract of dried calyx of sour tea on polygenic dyslipidemia. This clinical trial was done on 43 adults (30-60 years old) with polygenic dyslipidemia that were randomly assigned to the intervention and control groups. The control group was trained in lifestyle modifications at baseline. The intervention group was trained for lifestyle modifications at baseline and received two cups of sour tea daily, and both groups were followed up for 12 weeks. Lipid profile was evaluated at baseline, and six and 12 weeks following the intervention. In addition, dietary and physical activity assessed at baseline for twelve weeks. Mean concentration of total cholesterol, HDL-C and LDL-C significantly decreased by up to 9.46%, 8.33%, and 9.80%, respectively, after 12 weeks in the intervention group in comparison to their baseline values. However, LDL-C/HDL-C ratio significantly increased by up to 3.15%, following 12 weeks in the control group in comparison to their baseline values. This study showed no difference in lipid profiles between the two groups, except for HDL-C concentrations. sour tea may have significant positive effects on lipid profile of polygenic dyslipidemia subjects and these effect might be attributed to its anthocyanins and inflation factor content. Therefore, sour tea intake with recommended dietary patterns and physical activity can be useful in regulation of lipid profile in patients with polygenic dyslipidemia.

CHAMP: Cognitive behaviour therapy for health anxiety in medical patients, a randomised controlled trial

PubMed Central

2011-01-01

Background Abnormal health anxiety, also called hypochondriasis, has been successfully treated by cognitive behaviour therapy (CBT) in patients recruited from primary care, but only one pilot trial has been carried out among those attending secondary medical clinics where health anxiety is likely to be more common and have a greater impact on services. The CHAMP study extends this work to examine both the clinical and cost effectiveness of CBT in this population. Method/Design The study is a randomized controlled trial with two parallel arms and equal randomization of 466 eligible patients (assuming a 20% drop-out) to an active treatment group of 5-10 sessions of cognitive behaviour therapy and to a control group. The aim at baseline, after completion of all assessments but before randomization, was to give a standard simple explanation of the nature of health anxiety for all participants. Subsequently the control group was to receive whatever care might usually be available in the clinics, which is normally a combination of clinical assessment, appropriate tests and reassurance. Those allocated to the active treatment group were planned to receive between 5 and 10 sessions of an adapted form of cognitive behaviour therapy based on the Salkovskis/Warwick model, in which a set of treatment strategies are chosen aimed at helping patients understand the factors that drive and maintain health anxiety. The therapy was planned to be given by graduate research workers, nurses or other health professionals trained for this intervention whom would also have their competence assessed independently during the course of treatment. The primary outcome is reduction in health anxiety symptoms after one year and the main secondary outcome is the cost of care after two years. Discussion This represents the first trial of adapted cognitive behaviour therapy in health anxiety that is large enough to test not only the clinical benefits of treatment but also whether the cost of treatment is offset by savings from reduced use of other health services in comparison to the control group. Cognitive behaviour therapy for Health Anxiety in Medical Patients (CHAMP) Trial registration Current Controlled Trials ISRCTN14565822 PMID:21672205

Relationship of body mass index and psychosocial factors on physical activity in underserved adolescent boys and girls.

PubMed

Kitzman-Ulrich, Heather; Wilson, Dawn K; Van Horn, M Lee; Lawman, Hannah G

2010-09-01

Previous research indicates that body mass index (BMI) and sex are important factors in understanding physical activity (PA) levels. The present study examined the influence of BMI on psychosocial variables (self-efficacy, social support) and PA in underserved (ethnic minority, low income) boys in comparison with girls. Participants (N = 669; 56% girls; 74% African American) were recruited from the "Active by Choice Today" trial. BMI ʐ score was calculated from objectively collected height and weight data, and PA was assessed with 7-day accelerometry estimates. Self-report questionnaires were used to measure self-efficacy and social support (family, peers) for PA. A 3-way interaction between BMI z score, sex, and family support on PA was shown such that family support was positively associated with PA in normal-weight but not overweight or obese boys, and was not associated with PA in girls. Self-efficacy had the largest effect size related to PA in comparison with the other psychosocial variables studied. Self-efficacy was found to be an important variable related to PA in underserved youth. Future studies should evaluate possible barriers to PA in girls, and overweight youth, to provide more effective family support strategies for underserved adolescents' PA. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Outcomes from the Body & Soul Clinical Trials Project: A university-church partnership to improve African American enrollment in a clinical trial registry

PubMed Central

Langford, Aisha T.; Resnicow, Ken; Beasley, Derrick D.

2014-01-01

Objectives Historically, African Americans have been underrepresented in clinical trials (CTs) compared to whites. A growing number of research institutions have created CT registries to match volunteers with appropriate studies. In a sample of 745 African Americans from 16 churches, we tested the impact of a culturally tailored intervention aimed at increasing enrollment in a university-based CT registry. Methods Half of the churches received a culturally tailored CT education program (intervention) and half of the churches received a program about healthy eating (comparison). The main outcomes were the odds of posttest self-reported enrollment and verified enrollment. Using linear regression, posttest willingness to participate in a CT was also assessed. Results Odds of verified enrollment were higher in the intervention than comparison group (OR= 2.95, 95% CI: 1.33–6.5, p=0.01). Posttest self-reported enrollment in the registry was also higher among the intervention group than comparison group members (OR=1.94, 95% CI: 1.08–3.47, p=0.03). Willingness to participate in a future CT was higher in the intervention group (β=0.74, p=0.02). Conclusions A culturally tailored education program about CTs can increase enrollment of African Americans in a university-based clinical trials registry. Practice implications Community engagement and health education workshops may improve minority CT enrollment over time. PMID:25468392

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis

PubMed Central

Siriwardena, Ajith K; Mason, James M; Balachandra, Srinivasan; Bagul, Anil; Galloway, Simon; Formela, Laura; Hardman, Jonathan G; Jamdar, Saurabh

2007-01-01

Background Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. Methods We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n‐acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty‐three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE‐II score and hospital site, and delivered groups that were similar at baseline. Results Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. Conclusions This study provides no evidence to justify continued use of n‐acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. PMID:17356040

Comparison of timing and force control of foot tapping between elderly and young subjects.

PubMed

Takimoto, Koji; Takebayashi, Hideaki; Miyamoto, Kenzo; Takuma, Yutaka; Inoue, Yoshikazu; Miyamoto, Shoko; Okabe, Takao; Okuda, Takahiro; Kaba, Hideto

2016-06-01

[Purpose] To examine the ability of young and elderly individuals to control the timing and force of periodic sequential foot tapping. [Subjects and Methods] Participants were 10 young (age, 22.1 ± 4.3 years) and 10 elderly individuals (74.8 ± 6.7 years) who were healthy and active. The foot tapping task consisted of practice (stimulus-synchronized tapping with visual feedback) and recall trials (self-paced tapping without visual feedback), periodically performed in this order, at 500-, 1,000-, and 2,000-ms target interstimulus-onset intervals, with a target force of 20% maximum voluntary contraction of the ankle plantar-flexor muscle. [Results] The coefficients of variation of force and intertap interval, used for quantifying the steadiness of the trials, were significantly greater in the elderly than in the young individuals. At the 500-ms interstimulus-onset interval, age-related effects were observed on the normalized mean absolute error of force, which was used to quantify the accuracy of the trials. The coefficients of variation of intertap interval for elderly individuals were significantly greater in the practice than in the recall trials at the 500- and 1,000-ms interstimulus-onset intervals. [Conclusion] The elderly individuals exhibited greater force and timing variability than the young individuals and showed impaired visuomotor processing during foot tapping sequences.

Comparison of clinical and biochemical markers of dehydration with the clinical dehydration scale in children: a case comparison trial

PubMed Central

2014-01-01

Background The clinical dehydration scale (CDS) is a quick, easy-to-use tool with 4 clinical items and a score of 1–8 that serves to classify dehydration in children with gastroenteritis as no, some or moderate/severe dehydration. Studies validating the CDS (Friedman JN) with a comparison group remain elusive. We hypothesized that the CDS correlates with a wide spectrum of established markers of dehydration, making it an appropriate and easy-to-use clinical tool. Methods This study was designed as a prospective double-cohort trial in a single tertiary care center. Children with diarrhea and vomiting, who clinically required intravenous fluids for rehydration, were compared with minor trauma patients who required intravenous needling for conscious sedation. We compared the CDS with clinical and urinary markers (urinary electrolytes, proteins, ratios and fractional excretions) for dehydration in both groups using receiver operating characteristic (ROC) curves to determine the area under the curve (AUC). Results We enrolled 73 children (male = 36) in the dehydration group and 143 (male = 105) in the comparison group. Median age was 32 months (range 3–214) in the dehydration and 96 months (range 2.6-214 months, p < 0.0001) in the trauma group. Median CDS was 3 (range 0–8) within the dehydration group and 0 in the comparison group (p < 0.0001). The following parameters were statistically significant (p < 0.05) between the comparison group and the dehydrated group: difference in heart rate, diastolic blood pressure, urine sodium/potassium ratio, urine sodium, fractional sodium excretion, serum bicarbonate, and creatinine measurements. The best markers for dehydration were urine Na and serum bicarbonate (ROC AUC = 0.798 and 0.821, respectively). CDS was most closely correlated with serum bicarbonate (Pearson r = -0.3696, p = 0.002). Conclusion Although serum bicarbonate is not the gold standard for dehydration, this study provides further evidence for the usefulness of the CDS as a dehydration marker in children. Trial registration Registered at ClinicalTrials.gov (NCT00462527) on April 18, 2007. PMID:24935348

Comparison of Glucose Lowering Effect of Metformin and Acarbose in Type 2 Diabetes Mellitus: A Meta-Analysis

PubMed Central

Gu, Shuyan; Shi, Jihao; Tang, Zhiliu; Sawhney, Monika; Hu, Huimei; Shi, Lizheng; Fonseca, Vivian; Dong, Hengjin

2015-01-01

Background Metformin is the first-line oral hypoglycemic agent for type 2 diabetes mellitus recommended by international guidelines. However, little information exists comparing it with acarbose which is also commonly used in China. This study expanded knowledge by combining direct and indirect evidence to ascertain the glucose lowering effects of both drugs. Methods PubMed (1980- December 2013) and China National Knowledge Infrastructure databases (1994-January 2014) were systematically searched for eligible randomized controlled trials from Chinese and English literatures. Meta-analysis was conducted to estimate the glucose lowering effects of metformin vs. acarbose, or either of them vs. common comparators (placebo or sulphonylureas), using random- and fixed-effect models. Bucher method with indirect treatment comparison calculator was applied to convert the summary estimates from the meta-analyses into weighted-mean-difference (WMD) and 95% confidence intervals (CIs) to represent the comparative efficacy between metformin and acarbose. Results A total of 75 studies were included in the analysis. In direct comparison (8 trials), metformin reduced glycosylated hemoglobin (HbA1c) by 0.06% more than acarbose, with no significant difference (WMD,-0.06%; 95% CI, -0.32% to 0.20%). In indirect comparisons (67 trials), by using placebo and sulphonylureas as common comparators, metformin achieved significant HbA1c reduction than acarbose, by -0.38% (WMD,-0.38%, 95% CI, -0.736% to -0.024%) and -0.34% (WMD, -0.34%, 95% CI, -0.651% to -0.029%) respectively. Conclusion The glucose lowering effects of metformin monotherapy and acarbose monotherapy are the same by direct comparison, while metformin is a little better by indirect comparison. This implies that the effect of metformin is at least as good as acarbose's. PMID:25961824

Comparison of glucose lowering effect of metformin and acarbose in type 2 diabetes mellitus: a meta-analysis.

PubMed

Gu, Shuyan; Shi, Jihao; Tang, Zhiliu; Sawhney, Monika; Hu, Huimei; Shi, Lizheng; Fonseca, Vivian; Dong, Hengjin

2015-01-01

Metformin is the first-line oral hypoglycemic agent for type 2 diabetes mellitus recommended by international guidelines. However, little information exists comparing it with acarbose which is also commonly used in China. This study expanded knowledge by combining direct and indirect evidence to ascertain the glucose lowering effects of both drugs. PubMed (1980- December 2013) and China National Knowledge Infrastructure databases (1994-January 2014) were systematically searched for eligible randomized controlled trials from Chinese and English literatures. Meta-analysis was conducted to estimate the glucose lowering effects of metformin vs. acarbose, or either of them vs. common comparators (placebo or sulphonylureas), using random- and fixed-effect models. Bucher method with indirect treatment comparison calculator was applied to convert the summary estimates from the meta-analyses into weighted-mean-difference (WMD) and 95% confidence intervals (CIs) to represent the comparative efficacy between metformin and acarbose. A total of 75 studies were included in the analysis. In direct comparison (8 trials), metformin reduced glycosylated hemoglobin (HbA1c) by 0.06% more than acarbose, with no significant difference (WMD,-0.06%; 95% CI, -0.32% to 0.20%). In indirect comparisons (67 trials), by using placebo and sulphonylureas as common comparators, metformin achieved significant HbA1c reduction than acarbose, by -0.38% (WMD,-0.38%, 95% CI, -0.736% to -0.024%) and -0.34% (WMD, -0.34%, 95% CI, -0.651% to -0.029%) respectively. The glucose lowering effects of metformin monotherapy and acarbose monotherapy are the same by direct comparison, while metformin is a little better by indirect comparison. This implies that the effect of metformin is at least as good as acarbose's.

How many research nurses for how many clinical trials in an oncology setting? Definition of the Nursing Time Required by Clinical Trial-Assessment Tool (NTRCT-AT).

PubMed

Milani, Alessandra; Mazzocco, Ketti; Stucchi, Sara; Magon, Giorgio; Pravettoni, Gabriella; Passoni, Claudia; Ciccarelli, Chiara; Tonali, Alessandra; Profeta, Teresa; Saiani, Luisa

2017-02-01

Few resources are available to quantify clinical trial-associated workload, needed to guide staffing and budgetary planning. The aim of the study is to describe a tool to measure clinical trials nurses' workload expressed in time spent to complete core activities. Clinical trials nurses drew up a list of nursing core activities, integrating results from literature searches with personal experience. The final 30 core activities were timed for each research nurse by an outside observer during daily practice in May and June 2014. Average times spent by nurses for each activity were calculated. The "Nursing Time Required by Clinical Trial-Assessment Tool" was created as an electronic sheet that combines the average times per specified activities and mathematic functions to return the total estimated time required by a research nurse for each specific trial. The tool was tested retrospectively on 141 clinical trials. The increasing complexity of clinical research requires structured approaches to determine workforce requirements. This study provides a tool to describe the activities of a clinical trials nurse and to estimate the associated time required to deliver individual trials. The application of the proposed tool in clinical research practice could provide a consistent structure for clinical trials nursing workload estimation internationally. © 2016 John Wiley & Sons Australia, Ltd.

Adherence to physical activity guidelines and functional fitness of elderly women, using objective measurement.

PubMed

Nawrocka, Agnieszka; Mynarski, Władysław; Cholewa, Jarosław

2017-12-23

Physical activity is an important factor in maintaining the health and functional fitness of elderly people. The aim of the study was to determine the number of senior women meeting the physical activity guidelines, and their level of functional fitness in comparison to women who are not sufficiently physically active. The study involved 61 women, aged 60-75. Physical activity was monitored on seven consecutive days of the week, using a triaxial accelerometer ActiGraph GT3X. Results of the assessment of physical activity were verified against the Global Recommendations of Physical Activity for Health. The Senior Fitness Test (Fullerton Test) was used to evaluate functional fitness. In the studied group, 36.1% achieved the recommended level of physical activity. All those examined mainly undertook physical activity of low intensity. Vigorous physical activity during the week was noted in only 6 seniors. Women who met the recommendations of physical activity achieved significantly better results in test trials, e.g. Chair Stands, Up and Go, Six Minute Step Test. Adherence to physical activity guidelines was associated with better functional fitness of older women. However, less than half of the examined seniors met the Global Recommendations on Physical Activity for Health.

A Biomechanical Comparison of Proportional Electromyography Control to Biological Torque Control Using a Powered Hip Exoskeleton.

PubMed

Young, Aaron J; Gannon, Hannah; Ferris, Daniel P

2017-01-01

Despite a large increase in robotic exoskeleton research, there are few studies that have examined human performance with different control strategies on the same exoskeleton device. Direct comparison studies are needed to determine how users respond to different types of control. The purpose of this study was to compare user performance using a robotic hip exoskeleton with two different controllers: a controller that targeted a biological hip torque profile and a proportional myoelectric controller. We tested both control approaches on 10 able-bodied subjects using a pneumatically powered hip exoskeleton. The state machine controller targeted a biological hip torque profile. The myoelectric controller used electromyography (EMG) of lower limb muscles to produce a proportional control signal for the hip exoskeleton. Each subject performed two 30-min exoskeleton walking trials (1.0 m/s) using each controller and a 10-min trial with the exoskeleton unpowered. During each trial, we measured subjects' metabolic cost of walking, lower limb EMG profiles, and joint kinematics and kinetics (torques and powers) using a force treadmill and motion capture. Compared to unassisted walking in the exoskeleton, myoelectric control significantly reduced metabolic cost by 13% ( p  = 0.005) and biological hip torque control reduced metabolic cost by 7% ( p  = 0.261). Subjects reduced muscle activity relative to the unpowered condition for a greater number of lower limb muscles using myoelectric control compared to the biological hip torque control. More subjects subjectively preferred the myoelectric controller to the biological hip torque control. Myoelectric control had more advantages (metabolic cost and muscle activity reduction) compared to a controller that targeted a biological torque profile for walking with a robotic hip exoskeleton. However, these results were obtained with a single exoskeleton device with specific control configurations while level walking at a single speed. Further testing on different exoskeleton hardware and with more varied experimental protocols, such as testing over multiple types of terrain, is needed to fully elucidate the potential benefits of myoelectric control for exoskeleton technology.

Material incentives and enablers in the management of tuberculosis.

PubMed

Lutge, Elizabeth E; Wiysonge, Charles Shey; Knight, Stephen E; Volmink, Jimmy

2012-01-18

Patient adherence to medications, particularly for conditions requiring prolonged treatment such as tuberculosis, is frequently less than ideal, and can result in poor treatment outcomes. Material incentives (given as cash, vouchers and tokens), have been used to improve adherence. To assess the effects of material incentives in people undergoing diagnostic testing, or receiving prophylactic or curative therapy, for tuberculosis. We undertook a comprehensive search of the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; Science Citation Index; and reference lists of relevant publications; to 22 June 2011. Randomized controlled trials of material incentives in patients being investigated for tuberculosis, or on treatment for latent or active disease. At least two authors independently screened and selected studies, extracted data, and assessed the risk of bias. The effects of interventions are compared using risk ratios (RR), and presented with 95% confidence intervals (CI). The quality of the evidence was assessed using GRADE. We identified 11 eligible studies. Ten were conducted in the USA: in adolescents (one trial), in injection drug or cocaine users (four trials), in homeless adults (three trials), and in prisoners (two trials). One additional trial recruited malnourished men receiving active treatment for tuberculosis in Timor-Leste.Material incentives may increase the return rate for reading of tuberculin skin test results compared to normal care (two trials, 1371 participants: RR 2.16, 95% CI 1.41 to 3.29, low quality evidence).Similarly, incentives probably improve clinic re-attendance for initiation or continuation of antituberculosis prophylaxis (three trials, 595 participants: RR 1.58, 95% CI 1.27 to 1.96, moderate quality evidence), and may improve subsequent completion of prophylaxis in some settings (three trials, 869 participants: RR 1.79, 95% CI 0.70 to 4.58, low quality evidence).We currently don't know if incentives can improve long-term adherence and completion of antituberculosis treatment for active disease. Only one trial has assessed this and the incentive, given as a daily hot meal, was not well received by the population due to the inconvenience of attending the clinic at midday (one trial, 265 participants, RR 0.98, 95%CI 0.86 to 1.12, very low quality evidence).Several trials have compared different forms or levels of incentive. These comparisons remain limited to single trials and robust conclusions cannot be made. In summary, cash incentives may be more effective than non-cash incentives (return for test results: one trial, 651 participants: RR 1.13, 95%CI 1.07 to 1.19, low quality evidence, adherence to tuberculosis prophylaxis: one trial, 141 participants: RR 1.26, 95%CI 1.02 to 1.56, low quality evidence) and higher amounts of cash may be more effective than lower amounts (return for test results: one trial, 404 participants: RR 1.08, 95%CI 1.01 to 1.16, low quality evidence).Material incentives may also be more effective than motivational education at improving return for tuberculin skin test results (low quality evidence), but may be no more effective than peer counselling, or structured education at improving continuation or completion of prophylaxis (low quality evidence). There is limited evidence to support the use of material incentives to improve return rates for tuberculosis diagnostic test results and adherence to antituberculosis preventive therapy. The data are currently limited to trials among predominantly male drug users, homeless, and prisoner subpopulations in the USA, and therefore the results are not easily generalised to the wider adult population, or to low- and middle-income countries, where the tuberculosis burden is highest.Further high-quality studies are needed to assess both the costs and effectiveness of incentives to improve adherence to long-term treatment of tuberculosis.

The Prostate Cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy with watchful waiting for men with clinically localized prostate cancer.

PubMed

Wilt, Timothy J

2012-12-01

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. In the United States, 90% of men with prostate cancer are more than age 60 years, diagnosed by early detection with the prostate-specific antigen (PSA) blood test, and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting (WW), surgery to remove the prostate gland (radical prostatectomy), external-beam radiation therapy and interstitial radiation therapy (brachytherapy), and androgen deprivation. Little is known about the relative effectiveness and harms of treatments because of the paucity of randomized controlled trials. The Department of Veterans Affairs/National Cancer Institute/Agency for Healthcare Research and Quality Cooperative Studies Program Study #407:Prostate Cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy with WW in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods, and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy vs WW conducted in Scandinavia. We screened 13 022 men with prostate cancer at 52 US medical centers for potential enrollment. From these, 5023 met initial age, comorbidity, and disease eligibility criteria, and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African American. Approximately 85% reported that they were fully active. The median PSA was 7.8ng/mL (mean 10.2ng/mL). In three-fourths of men, the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade, and tumor stage, it was found that approximately 40% had low-risk, 34% had medium-risk, and 21% had high-risk prostate cancer based on local histopathology. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the United States and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared with WW for men with predominately PSA-detected clinically localized prostate cancer.

The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer.

PubMed

Wilt, Timothy J; Brawer, Michael K; Barry, Michael J; Jones, Karen M; Kwon, Young; Gingrich, Jeffrey R; Aronson, William J; Nsouli, Imad; Iyer, Padmini; Cartagena, Ruben; Snider, Glenn; Roehrborn, Claus; Fox, Steven

2009-01-01

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. Ninety percent of men with prostate cancer are over aged 60 years, diagnosed by early detection with the prostate specific antigen (PSA) blood test and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting surgery to remove the prostate gland (radical prostatectomy), external beam radiation therapy and interstitial radiation therapy (brachytherapy) and androgen deprivation. Little is known about the relative effectiveness and harms of treatments due to the paucity of randomized controlled trials. The VA/NCI/AHRQ Cooperative Studies Program Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer. We describe the study rationale, design, recruitment methods and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy versus watchful waiting conducted in Scandinavia. We screened 13,022 men with prostate cancer at 52 United States medical centers for potential enrollment. From these, 5023 met initial age, comorbidity and disease eligibility criteria and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African-American. Approximately 85% reported they were fully active. The median prostate specific antigen (PSA) was 7.8 ng/mL (mean 10.2 ng/mL). In three-fourths of men the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade and tumor stage, approximately 43% had low risk, 36% had medium risk and 20% had high-risk prostate cancer. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the U.S. and quite different from men in the Scandinavian trial. PIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared to watchful waiting for men with predominately PSA detected clinically localized prostate cancer.

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

PubMed

Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-07-01

Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological active placebo control interventions are rarely used in randomized clinical trials, but they constitute a methodological tool which merits serious consideration. We suggest that active placebos are used more often in trials of drugs with noticeable side effects, especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high. Copyright © 2017 Elsevier Inc. All rights reserved.

CHILE: Outcomes of a group randomized controlled trial of an intervention to prevent obesity in preschool Hispanic and American Indian children.

PubMed

Davis, Sally M; Myers, Orrin B; Cruz, Theresa H; Morshed, Alexandra B; Canaca, Glenda F; Keane, Patricia C; O'Donald, Elena R

2016-08-01

We examined the outcomes of the Child Health Initiative for Lifelong Eating and Exercise (CHILE) study, a group randomized controlled trial to design, implement, and test the efficacy of a trans-community intervention to prevent obesity in children enrolled in Head Start centers in rural American Indian and Hispanic communities in New Mexico. CHILE was a 5-year evidence-based intervention that used a socioecological approach to improving dietary intake and increasing physical activity of 1898 children. The intervention included a classroom curriculum, teacher and food service training, family engagement, grocery store participation, and healthcare provider support. Height and weight measurements were obtained four times (fall of 2008, spring and fall of 2009, and spring of 2010), and body mass index (BMI) z-scores in the intervention and comparison groups were compared. At baseline, demographic characteristics in the comparison and intervention groups were similar, and 33% of all the children assessed were obese or overweight. At the end of the intervention, there was no significant difference between the two groups in BMI z-scores. Obesity prevention research among Hispanic and AI preschool children in rural communities is challenging and complex. Although the CHILE intervention was implemented successfully, changes in overweight and obesity may take longer than 2years to achieve. Copyright © 2016 Elsevier Inc. All rights reserved.

Improvements in Cardiovascular Risk Factors in Young Adults in a Randomized Trial of Approaches to Weight Gain Prevention

PubMed Central

Wing, Rena R.; Tate, Deborah F.; Garcia, Katelyn R.; Bahnson, Judy; Lewis, Cora E.; Espeland, Mark A.

2017-01-01

Objective Weight gain occurs commonly in young adults and increases cardiovascular (CVD) risk. We previously reported that two self-regulation interventions reduced weight gain relative to control. Here we examine whether these interventions also benefit CVD risk factors. Methods SNAP (Study of Novel Approaches to Weight Gain Prevention) was a randomized trial in 2 academic settings (N=599; 18–35 years; body mass index 21–30 kg/m2) comparing two interventions (Self-Regulation with Small Changes; Self-Regulation with Large Changes) and Control. Small Changes taught participants to make daily small changes (approximately 100 calorie) in intake and activity. Large Changes taught participants to initially lose 5–10 pounds to buffer anticipated weight gains. CVD risk factors were assessed at baseline and 2 years in 471 participants. Results Although Large Changes was associated with more beneficial changes in glucose, insulin, and HOMA-IR than Control, these differences were not significant after adjusting for multiple comparisons or 2-year weight change. Comparison of participants grouped by percent weight change baseline to 2 years showed significant differences for several CVD risk factors, with no interaction with treatment condition. Conclusions Magnitude of weight change, rather than specific weight gain prevention interventions, was related to changes in CVD risk factors in young adults. PMID:28782918

Hatha Yoga Practice Improves Attention and Processing Speed in Older Adults: Results from an 8-Week Randomized Control Trial.

PubMed

Gothe, Neha P; Kramer, Arthur F; McAuley, Edward

2017-01-01

Age-related cognitive decline is well documented across various aspects of cognitive function, including attention and processing speed, and lifestyle behaviors such as physical activity play an important role in preventing cognitive decline and maintaining or even improving cognitive function. The purpose of this study was to evaluate the effects of an 8-week Hatha yoga intervention on attention and processing speed among older adults. Participants (n = 118; mean age, 62 ± 5.59) were randomly assigned to an 8-week Hatha yoga group or a stretching control group and completed cognitive assessments-Attention Network Task, Trail Making Test parts A and B, and Pattern Comparison Test-at baseline and after the 8-week intervention. Analyses of covariance revealed significantly faster reaction times for the yoga group on the Attention Network Task's neutral, congruent, and incongruent conditions (p ≤ 0.04). The yoga intervention also improved participants' visuospatial and perceptual processing on the Trail Making Test part B (p = 0.002) and pattern comparison (p < 0.001) tests. These results suggest that yoga practice that includes postures, breathing, and meditative exercises lead to improved attentional and information processing abilities. Although the underlying mechanisms remain largely speculative, more systematic trials are needed to explore the extent of cognitive benefits and their neurobiological mechanisms.

Comparison of data transformation procedures to enhance topographical accuracy in time-series analysis of the human EEG.

PubMed

Hauk, O; Keil, A; Elbert, T; Müller, M M

2002-01-30

We describe a methodology to apply current source density (CSD) and minimum norm (MN) estimation as pre-processing tools for time-series analysis of single trial EEG data. The performance of these methods is compared for the case of wavelet time-frequency analysis of simulated gamma-band activity. A reasonable comparison of CSD and MN on the single trial level requires regularization such that the corresponding transformed data sets have similar signal-to-noise ratios (SNRs). For region-of-interest approaches, it should be possible to optimize the SNR for single estimates rather than for the whole distributed solution. An effective implementation of the MN method is described. Simulated data sets were created by modulating the strengths of a radial and a tangential test dipole with wavelets in the frequency range of the gamma band, superimposed with simulated spatially uncorrelated noise. The MN and CSD transformed data sets as well as the average reference (AR) representation were subjected to wavelet frequency-domain analysis, and power spectra were mapped for relevant frequency bands. For both CSD and MN, the influence of noise can be sufficiently suppressed by regularization to yield meaningful information, but only MN represents both radial and tangential dipole sources appropriately as single peaks. Therefore, when relating wavelet power spectrum topographies to their neuronal generators, MN should be preferred.

The Efficacy and Acceptability of Third-Wave Behavioral and Cognitive eHealth Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

O'Connor, Martin; Munnelly, Anita; Whelan, Robert; McHugh, Louise

2018-05-01

eHealth is an innovative method of delivering therapeutic content with the potential to improve access to third-wave behaviural and cognitive therapies. This systematic review and meta-analysis aimed to determine the efficacy and acceptability of third-wave eHealth treatments in improving mental health outcomes. A comprehensive search of electronic bibliographic databases including PubMed, PsycINFO, Web of Science, and CENTRAL was conducted to identify randomized controlled trials of third-wave treatments in which eHealth was the main component. Twenty-one studies were included in the review. Meta-analyses revealed that third-wave eHealth significantly outperformed inactive control conditions in improving anxiety, depression, and quality-of-life outcomes and active control conditions in alleviating anxiety and depression with small to medium effect sizes. No statistically significant differences were found relative to comparison interventions. Findings from a narrative synthesis of participant evaluation outcomes and meta-analysis of participant attrition rates provided preliminary support for the acceptability of third-wave eHealth. Third-wave eHealth treatments are efficacious in improving mental health outcomes including anxiety, depression, and quality of life, but not more so than comparison interventions. Preliminary evidence from indices of participant evaluation and attrition rates supports the acceptability of these treatments. Copyright © 2017. Published by Elsevier Ltd.

Radiotherapy for Vestibular Schwannomas: A Critical Review

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

Murphy, Erin S., E-mail: murphye3@ccf.or; Suh, John H.

2011-03-15

Vestibular schwannomas are slow-growing tumors of the myelin-forming cells that cover cranial nerve VIII. The treatment options for patients with vestibular schwannoma include active observation, surgical management, and radiotherapy. However, the optimal treatment choice remains controversial. We have reviewed the available data and summarized the radiotherapeutic options, including single-session stereotactic radiosurgery, fractionated conventional radiotherapy, fractionated stereotactic radiotherapy, and proton beam therapy. The comparisons of the various radiotherapy modalities have been based on single-institution experiences, which have shown excellent tumor control rates of 91-100%. Both stereotactic radiosurgery and fractionated stereotactic radiotherapy have successfully improved cranial nerve V and VII preservation tomore » >95%. The mixed data regarding the ideal hearing preservation therapy, inherent biases in patient selection, and differences in outcome analysis have made the comparison across radiotherapeutic modalities difficult. Early experience using proton therapy for vestibular schwannoma treatment demonstrated local control rates of 84-100% but disappointing hearing preservation rates of 33-42%. Efforts to improve radiotherapy delivery will focus on refined dosimetry with the goal of reducing the dose to the critical structures. As future randomized trials are unlikely, we suggest regimented pre- and post-treatment assessments, including validated evaluations of cranial nerves V, VII, and VIII, and quality of life assessments with long-term prospective follow-up. The results from such trials will enhance the understanding of therapy outcomes and improve our ability to inform patients.« less

COMBIT: protocol of a randomised comparison trial of COMbined modified constraint induced movement therapy and bimanual intensive training with distributed model of standard upper limb rehabilitation in children with congenital hemiplegia.

PubMed

Boyd, Roslyn N; Ziviani, Jenny; Sakzewski, Leanne; Miller, Laura; Bowden, Joanne; Cunnington, Ross; Ware, Robert; Guzzetta, Andrea; Al Macdonell, Richard; Jackson, Graeme D; Abbott, David F; Rose, Stephen

2013-06-28

Children with congenital hemiplegia often present with limitations in using their impaired upper limb which impacts on independence in activities of daily living, societal participation and quality of life. Traditional therapy has adopted a bimanual training approach (BIM) and more recently, modified constraint induced movement therapy (mCIMT) has emerged as a promising unimanual approach. Evidence of enhanced neuroplasticity following mCIMT suggests that the sequential application of mCIMT followed by bimanual training may optimise outcomes (Hybrid CIMT). It remains unclear whether more intensely delivered group based interventions (hCIMT) are superior to distributed models of individualised therapy. This study aims to determine the optimal density of upper limb training for children with congenital hemiplegia. A total of 50 children (25 in each group) with congenital hemiplegia will be recruited to participate in this randomized comparison trial. Children will be matched in pairs at baseline and randomly allocated to receive an intensive block group hybrid model of combined mCIMT followed by intensive bimanual training delivered in a day camp model (COMBiT; total dose 45 hours direct, 10 hours of indirect therapy), or a distributed model of standard occupational therapy and physiotherapy care (SC) over 12 weeks (total 45 hours direct and indirect therapy). Outcomes will be assessed at 13 weeks after commencement, and retention of effects tested at 26 weeks. The primary outcomes will be bimanual coordination and unimanual upper-limb capacity. Secondary outcomes will be participation and quality of life. Advanced brain imaging will assess neurovascular changes in response to treatment. Analysis will follow standard principles for RCTs, using two-group comparisons on all participants on an intention-to-treat basis. Comparisons will be between treatment groups using generalized linear models. ACTRN12613000181707.

Short-term combined effects of thoracic spine thrust manipulation and cervical spine nonthrust manipulation in individuals with mechanical neck pain: a randomized clinical trial.

PubMed

Masaracchio, Michael; Cleland, Joshua A; Hellman, Madeleine; Hagins, Marshall

2013-03-01

Randomized clinical trial. To investigate the short-term effects of thoracic spine thrust manipulation combined with cervical spine nonthrust manipulation (experimental group) versus cervical spine nonthrust manipulation alone (comparison group) in individuals with mechanical neck pain. Research has demonstrated improved outcomes with both nonthrust manipulation directed at the cervical spine and thrust manipulation directed at the thoracic spine in patients with neck pain. Previous studies have not determined if thoracic spine thrust manipulation may increase benefits beyond those provided by cervical nonthrust manipulation alone. Sixty-four participants with mechanical neck pain were randomized into 1 of 2 groups, an experimental or comparison group. Both groups received 2 treatment sessions of cervical spine nonthrust manipulation and a home exercise program consisting of active range-of-motion exercises, and the experimental group received additional thoracic spine thrust manipulations. Outcome measures were collected at baseline and at a 1-week follow-up, and included the numeric pain rating scale, the Neck Disability Index, and the global rating of change. Participants in the experimental group demonstrated significantly greater improvements (P<.001) on both the numeric pain rating scale and Neck Disability Index at the 1-week follow-up compared to those in the comparison group. In addition, 31 of 33 (94%) participants in the experimental group, compared to 11 of 31 participants (35%) in the comparison group, indicated a global rating of change score of +4 or higher at the 1-week follow-up, with an associated number needed to treat of 2. Individuals with neck pain who received a combination of thoracic spine thrust manipulation and cervical spine nonthrust manipulation plus exercise demonstrated better overall short-term outcomes on the numeric pain rating scale, the Neck Disability Index, and the global rating of change.

Cannabis Abstinence During Treatment and One-Year Follow-Up: Relationship to Neural Activity in Men

PubMed Central

Kober, Hedy; DeVito, Elise E; DeLeone, Cameron M; Carroll, Kathleen M; Potenza, Marc N

2014-01-01

Cannabis is among the most frequently abused substances in the United States. Cognitive control is a contributory factor in the maintenance of substance-use disorders and may relate to treatment response. Therefore, we assessed whether cognitive-control-related neural activity before treatment differs between treatment-seeking cannabis-dependent and healthy individuals and relates to cannabis-abstinence measures during treatment and 1-year follow-up. Cannabis-dependent males (N=20) completed a functional magnetic resonance imaging (fMRI) cognitive-control (Stroop) task before a 12-week randomized controlled trial of cognitive–behavioral therapy and/or contingency management. A healthy-comparison group (N=20) also completed the fMRI task. Cannabis use was assessed by urine toxicology and self-report during treatment, and by self-report across a 1-year follow-up period (N=18). The cannabis-dependent group displayed diminished Stroop-related neural activity relative to the healthy-comparison group in multiple regions, including those strongly implicated in cognitive-control and addiction-related processes (eg, dorsolateral prefrontal cortex and ventral striatum). The groups did not differ significantly in response times (cannabis-dependent, N=12; healthy-comparison, N=14). Within the cannabis-dependent group, greater Stroop-related activity in regions including the dorsal anterior cingulate cortex was associated with less cannabis use during treatment. Greater activity in regions including the ventral striatum was associated with less cannabis use during 1-year posttreatment follow-up. These data suggest that lower cognitive-control-related neural activity in classic ‘control' regions (eg, dorsolateral prefrontal cortex and dorsal anterior cingulate) and classic ‘salience/reward/learning' regions (eg, ventral striatum) differentiates cannabis-dependent individuals from healthy individuals and relates to less abstinence within-treatment and during long-term follow-up. Clinically, results suggest that treatment development efforts that focus on enhancing cognitive control in addition to abstinence may improve treatment outcomes in cannabis dependence. PMID:24705568

Cannabis abstinence during treatment and one-year follow-up: relationship to neural activity in men.

PubMed

Kober, Hedy; DeVito, Elise E; DeLeone, Cameron M; Carroll, Kathleen M; Potenza, Marc N

2014-09-01

Cannabis is among the most frequently abused substances in the United States. Cognitive control is a contributory factor in the maintenance of substance-use disorders and may relate to treatment response. Therefore, we assessed whether cognitive-control-related neural activity before treatment differs between treatment-seeking cannabis-dependent and healthy individuals and relates to cannabis-abstinence measures during treatment and 1-year follow-up. Cannabis-dependent males (N=20) completed a functional magnetic resonance imaging (fMRI) cognitive-control (Stroop) task before a 12-week randomized controlled trial of cognitive-behavioral therapy and/or contingency management. A healthy-comparison group (N=20) also completed the fMRI task. Cannabis use was assessed by urine toxicology and self-report during treatment, and by self-report across a 1-year follow-up period (N=18). The cannabis-dependent group displayed diminished Stroop-related neural activity relative to the healthy-comparison group in multiple regions, including those strongly implicated in cognitive-control and addiction-related processes (eg, dorsolateral prefrontal cortex and ventral striatum). The groups did not differ significantly in response times (cannabis-dependent, N=12; healthy-comparison, N=14). Within the cannabis-dependent group, greater Stroop-related activity in regions including the dorsal anterior cingulate cortex was associated with less cannabis use during treatment. Greater activity in regions including the ventral striatum was associated with less cannabis use during 1-year posttreatment follow-up. These data suggest that lower cognitive-control-related neural activity in classic 'control' regions (eg, dorsolateral prefrontal cortex and dorsal anterior cingulate) and classic 'salience/reward/learning' regions (eg, ventral striatum) differentiates cannabis-dependent individuals from healthy individuals and relates to less abstinence within-treatment and during long-term follow-up. Clinically, results suggest that treatment development efforts that focus on enhancing cognitive control in addition to abstinence may improve treatment outcomes in cannabis dependence.

Shared care or nurse consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis (RA) outpatients with stable low disease-activity RA: cost-effectiveness based on a 2-year randomized trial.

PubMed

Sørensen, J; Primdahl, J; Horn, H C; Hørslev-Petersen, K

2015-01-01

To compare the cost-effectiveness of three types of follow-up for outpatients with stable low-activity rheumatoid arthritis (RA). In total, 287 patients were randomized to either planned rheumatologist consultations, shared care without planned consultations, or planned nurse consultations. Effectiveness measures included disease activity (Disease Activity Score based on 28 joint counts and C-reactive protein, DAS28-CRP), functional status (Health Assessment Questionnaire, HAQ), and health-related quality of life (EuroQol EQ-5D). Cost measures included activities in outpatient clinics and general practice, prescription and non-prescription medicine, dietary supplements, other health-care resources, and complementary and alternative care. Measures of effectiveness and costs were collected by self-reported questionnaires at inclusion and after 12 and 24 months. Incremental cost-effectiveness rates (ICERs) were estimated in comparison with rheumatologist consultations. Changes in disease activity, functional status, and health-related quality of life were not statistically significantly different for the three groups, although the mean scores were better for the shared care and nurse care groups compared with the rheumatologist group. Shared care and nurse care were non-significantly less costly than rheumatologist care. As both shared care and nurse care were associated with slightly better EQ-5D improvements and lower costs, they dominated rheumatologist care. At EUR 10,000 per quality-adjusted life year (QALY) threshold, shared care and nurse care were cost-effective with more than 90% probability. Nurse care was cost-effective in comparison with shared care with 75% probability. Shared care and nurse care seem to cost less but provide broadly similar health outcomes compared with rheumatologist outpatient care. However, it is still uncertain whether nurse care and shared care are cost-effective in comparison with rheumatologist outpatient care.

Working memory for vibrotactile frequencies: comparison of cortical activity in blind and sighted individuals.

PubMed

Burton, Harold; Sinclair, Robert J; Dixit, Sachin

2010-11-01

In blind, occipital cortex showed robust activation to nonvisual stimuli in many prior functional neuroimaging studies. The cognitive processes represented by these activations are not fully determined, although a verbal recognition memory role has been demonstrated. In congenitally blind and sighted (10 per group), we contrasted responses to a vibrotactile one-back frequency retention task with 5-s delays and a vibrotactile amplitude-change task; both tasks involved the same vibration parameters. The one-back paradigm required continuous updating for working memory (WM). Findings in both groups confirmed roles in WM for right hemisphere dorsolateral prefrontal (DLPFC) and dorsal/ventral attention components of posterior parietal cortex. Negative findings in bilateral ventrolateral prefrontal cortex suggested task performance without subvocalization. In bilateral occipital cortex, blind showed comparable positive responses to both tasks, whereas WM evoked large negative responses in sighted. Greater utilization of attention resources in blind were suggested as causing larger responses in dorsal and ventral attention systems, right DLPFC, and persistent responses across delays between trials in somatosensory and premotor cortex. In sighted, responses in somatosensory and premotor areas showed iterated peaks matched to stimulation trial intervals. The findings in occipital cortex of blind suggest that tactile activations do not represent cognitive operations for nonverbal WM task. However, these data suggest a role in sensory processing for tactile information in blind that parallels a similar contribution for visual stimuli in occipital cortex of sighted. © 2010 Wiley-Liss, Inc.

Squatting Exercises in Older Adults: Kinematic and Kinetic Comparisons

PubMed Central

FLANAGAN, SEAN; SALEM, GEORGE J.; WANG, MAN-YING; SANKER, SERENA E.; GREENDALE, GAIL A.

2012-01-01

Purpose Squatting activities may be used, within exercise programs, to preserve physical function in older adults. This study characterized the lower-extremity peak joint angles, peak moments, powers, work, impulse, and muscle recruitment patterns (electromyographic; EMG) associated with two types of squatting activities in elders. Methods Twenty-two healthy, older adults (ages 70–85) performed three trials each of: 1) a squat to a self-selected depth (normal squat; SQ) and 2) a squat onto a chair with a standardized height of 43.8 cm (chair squat; CSQ). Descending and ascending phase joint kinematics and kinetics were obtained using a motion analysis system and inverse dynamics techniques. Results were averaged across the three trials. A 2 × 2 (activity × phase) ANOVA with repeated measures was used to examine the biomechanical differences among the two activities and phases. EMG temporal characteristics were qualitatively examined. Results CSQ generated greater hip flexion angles, peak moments, power, and work, whereas SQ generated greater knee and ankle flexion angles, peak moments, power, and work. SQ generated a greater knee extensor impulse, a greater plantar flexor impulse and a greater total support impulse. The EMG temporal patterns were consistent with the kinetic data. Conclusions The results suggest that, with older adults, CSQ places greater demand on the hip extensors, whereas SQ places greater demand on the knee extensors and ankle plantar flexors. Clinicians may use these discriminate findings to more effectively target specific lower-extremity muscle groups when prescribing exercise for older adults. PMID:12673148

Tricyclic and Tetracyclic Antidepressants for the Prevention of Frequent Episodic or Chronic Tension-Type Headache in Adults: A Systematic Review and Meta-Analysis.

PubMed

Jackson, Jeffrey L; Mancuso, Josephine M; Nickoloff, Sarah; Bernstein, Rebecca; Kay, Cynthia

2017-12-01

Tension-type headaches are a common source of pain and suffering. Our purpose was to assess the efficacy of tricyclic (TCA) and tetracyclic antidepressants in the prophylactic treatment of tension-type headache. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the ISI Web of Science, and clinical trial registries through 11 March 2017 for randomized controlled studies of TCA or tetracyclic antidepressants in the prevention of tension-type headache in adults. Data were pooled using a random effects approach. Among 22 randomized controlled trials, eight included a placebo comparison and 19 compared at least two active treatments. Eight studies compared TCAs to placebo, four compared TCAs to selective serotonin reuptake inhibitors (SSRIs), and two trials compared TCAs to behavioral therapies. Two trials compared tetracyclics to placebo. Single trials compared TCAs to tetracyclics, buspirone, spinal manipulation, transcutaneous electrical stimulation, massage, and intra-oral orthotics. High-quality evidence suggests that TCAs were superior to placebo in reducing headache frequency (weighted mean differences (WMD): -4.8 headaches/month, 95% CI: -6.63 to -2.95) and number of analgesic medications consumed (WMD: -21.0 doses/month, 95% CI: -38.2 to -3.8). TCAs were more effective than SSRIs. Low-quality studies suggest that TCAs are superior to buspirone, but equivalent to behavioral therapy, spinal manipulation, intra-oral orthotics, and massage. Tetracyclics were no better than placebo for chronic tension-type headache. Tricyclic antidepressants are modestly effective in reducing chronic tension-type headache and are superior to buspirone. In limited studies, tetracyclics appear to be ineffective in the prophylactic treatment of chronic tension-type headache.

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

PubMed

Poulsen, Erik; Christensen, Henrik W; Roos, Ewa M; Vach, Werner; Overgaard, Søren; Hartvigsen, Jan

2011-05-04

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

Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis

PubMed Central

Monach, Paul A; Warner, Roscoe L; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Iklé, David; Kallenberg, Cees GM; Krischer, Jeffrey; Langford, Carol A; Mueller, Mark; Seo, Philip; St. Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Johnson, Kent J; Merkel, Peter A

2016-01-01

Objective To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation. Methods Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6 months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG)≥3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC). Results All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low. Conclusions Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV. PMID:22975753

Evidence regarding patient compliance with incentive spirometry interventions after cardiac, thoracic and abdominal surgeries: A systematic literature review.

PubMed

Narayanan, Aqilah Leela T; Hamid, Syed Rasul G Syed; Supriyanto, Eko

2016-01-01

Evidence regarding the effectiveness of incentive spirometry (ISy) on postoperative pulmonary outcomes after thoracic, cardiac and abdominal surgery remains inconclusive. This is attributed to various methodological issues inherent in ISy trials. Patient compliance has also been highlighted as a possible confounding factor; however, the status of evidence regarding patient compliance in these trials is unknown. To explore the status of evidence on patient compliance with ISy interventions in randomized controlled trials (RCTs) in the above contexts. A systematic search using MEDLINE, EMBASE and CINAHL databases was conducted to obtain relevant RCTs from 1972 to 2015 using the inclusion criteria. These were examined for specific ISy parameters, methods used for determining compliance and reporting on compliance. Main outcome measures were comparison of ISy parameters prescribed and assessed, and reporting on compliance. Thirty-six relevant RCTs were obtained. Six ISy parameters were identified in ISy prescriptions from these trials. Almost all (97.2%) of the trials had ISy prescriptions with specific parameters. Wilcoxon signed-rank test revealed that the ISy parameters assessed were significantly lower (Z=-5.433; P<0.001) than those prescribed; 66.7% of the trials indicated use of various methods to assess these parameters. Only six (16.7%) trials included reports on compliance; however, these were also incomprehensive. There is a scarcity and inconsistency of evidence regarding ISy compliance. Compliance data should be obtained using reliable and standardized methods to facilitate comparisons between and among trials. These should be reported comprehensively to facilitate valid inferences regarding ISy intervention effectiveness.

Comparison of noninferiority margins reported in protocols and publications showed incomplete and inconsistent reporting.

PubMed

Dekkers, Olaf M; Cevallos, Myriam; Bührer, Jonas; Poncet, Antoine; Ackermann Rau, Sabine; Perneger, Thomas V; Egger, Matthias

2015-05-01

To compare noninferiority margins defined in study protocols and trial registry records with margins reported in subsequent publications. Comparison of protocols of noninferiority trials submitted 2001 to 2005 to ethics committees in Switzerland and The Netherlands with corresponding publications and registry records. We searched MEDLINE via PubMed, the Cochrane Controlled Trials Register (Cochrane Library issue 01/2012), and Google Scholar in September 2013 to identify published reports, and the International Clinical Trials Registry Platform of the World Health Organization in March 2013 to identify registry records. Two readers recorded the noninferiority margin and other data using a standardized data-abstraction form. The margin was identical in study protocol and publication in 43 (80%) of 54 pairs of study protocols and articles. In the remaining pairs, reporting was inconsistent (five pairs, 9%), or the noninferiority margin was either not reported in the publication (five pairs, 9%) or not defined in the study protocol (one pair). The confidence interval or the exact P-value required to judge whether the result was compatible with noninferior, inferior, or superior efficacy was reported in 43 (80%) publications. Complete and consistent reporting of both noninferiority margin and confidence interval (or exact P-value) was present in 39 (72%) protocol-publication pairs. Twenty-nine trials (54%) were registered in trial registries, but only one registry record included the noninferiority margin. The reporting of noninferiority margins was incomplete and inconsistent with study protocols in a substantial proportion of published trials, and margins were rarely reported in trial registries. Copyright © 2015 Elsevier Inc. All rights reserved.

Evidence regarding patient compliance with incentive spirometry interventions after cardiac, thoracic and abdominal surgeries: A systematic literature review

PubMed Central

Narayanan, Aqilah Leela T; Hamid, Syed Rasul G Syed; Supriyanto, Eko

2016-01-01

BACKGROUND: Evidence regarding the effectiveness of incentive spirometry (ISy) on postoperative pulmonary outcomes after thoracic, cardiac and abdominal surgery remains inconclusive. This is attributed to various methodological issues inherent in ISy trials. Patient compliance has also been highlighted as a possible confounding factor; however, the status of evidence regarding patient compliance in these trials is unknown. OBJECTIVE: To explore the status of evidence on patient compliance with ISy interventions in randomized controlled trials (RCTs) in the above contexts. METHOD: A systematic search using MEDLINE, EMBASE and CINAHL databases was conducted to obtain relevant RCTs from 1972 to 2015 using the inclusion criteria. These were examined for specific ISy parameters, methods used for determining compliance and reporting on compliance. Main outcome measures were comparison of ISy parameters prescribed and assessed, and reporting on compliance. RESULTS: Thirty-six relevant RCTs were obtained. Six ISy parameters were identified in ISy prescriptions from these trials. Almost all (97.2%) of the trials had ISy prescriptions with specific parameters. Wilcoxon signed-rank test revealed that the ISy parameters assessed were significantly lower (Z=−5.433; P<0.001) than those prescribed; 66.7% of the trials indicated use of various methods to assess these parameters. Only six (16.7%) trials included reports on compliance; however, these were also incomprehensive. CONCLUSIONS: There is a scarcity and inconsistency of evidence regarding ISy compliance. Compliance data should be obtained using reliable and standardized methods to facilitate comparisons between and among trials. These should be reported comprehensively to facilitate valid inferences regarding ISy intervention effectiveness. PMID:26909010

Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

PubMed

Paschke, Lena M; Walter, Henrik; Steimke, Rosa; Ludwig, Vera U; Gaschler, Robert; Schubert, Torsten; Stelzel, Christine

2015-05-01

Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The block analysis revealed greater activity in gain and loss blocks compared to the neutral condition in most of these regions but no differences in the direct comparison of gain and loss blocks. These findings show that potential monetary gain and loss rely on different mechanisms: Gain was more effective in reducing the reaction time compared to potential loss. Brain data indicate that in the gain context attentional control is executed specifically in incongruent trials, whereas the loss context induces an unspecific increase of attentional control. These findings extend previous studies by providing evidence for diverging neural mechanisms for the effects of different types of motivation on attentional control, specifying the underlying activity patterns in task- and stimulus-related regions. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of two school-based programmes for health behaviour change: the Belo Horizonte Heart Study randomized trial.

PubMed

Ribeiro, Robespierre Q C; Alves, Luciana

2014-06-01

To assess the efficacy of two school-based programmes to promote students' willingness to engage in lifestyle changes related to eating habits and physical activity behaviours. Elementary school-based health promotion intervention, designed as a multicomponent experimental study, based on a behavioural epidemiological model. Nine intervention and eight comparative public and private elementary schools. The goal was to determine the impact on the longitudinally assessed outcomes of two programmes that addressed healthy nutrition and active living in a cohort of 2038 children. The evaluations used pre-intervention and follow-up student surveys that were based on the Transtheoretical Model of the stages of behaviour change. In the intervention group, there were significant (P < 0·001) differences between the pre- and post-intervention times in the stages of change, with a reduction in the percentage of children at the pre-contemplation and contemplation stages and increased percentages at the preparation, action and maintenance stages, leading to healthier behaviours in fatty food consumption, fruit and vegetable consumption, physical activity and time spent in sedentary activities. The determinants of the behaviour stage were the intervention programme, the type of school and the presence of motivated teachers. The comparison group did not show significant differences between the pre- and post-intervention times for any of the stages of behaviour. The intervention programme encouraged the students to make healthy lifestyle choices related to eating habits and physical activity behaviours.

Sedentary behavior and physical activity in youth with recent onset of type 2 diabetes.

PubMed

Kriska, Andrea; Delahanty, Linda; Edelstein, Sharon; Amodei, Nancy; Chadwick, Jennifer; Copeland, Kenneth; Galvin, Bryan; El ghormli, Laure; Haymond, Morey; Kelsey, Megan; Lassiter, Chad; Mayer-Davis, Elizabeth; Milaszewski, Kerry; Syme, Amy

2013-03-01

With the rise of type 2 diabetes in youth, it is critical to investigate factors such as physical activity (PA) and time spent sedentary that may be contributing to this public health problem. This article describes PA and sedentary time in a large cohort of youth with type 2 diabetes and compares these levels with other large-scale investigations. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial is a study in 699 youth, recruited from 15 US clinical centers, aged 10 to 17 years with <2 years of type 2 diabetes and a BMI ≥85th percentile. In comparison with the subset of the NHANES cohort who were obese (BMI ≥95th percentile), TODAY youth spent significantly more time being sedentary (difference averaging 56 minutes per day; P < .001) as assessed by accelerometry. Although moderate to vigorous activity levels in both obese cohorts for all age groups were exceptionally low, younger TODAY boys were still significantly less active than similarly aged NHANES youth. Comparisons between the TODAY girls and other investigations suggest that the TODAY girls also had relatively lower PA and fitness levels. Adolescents with type 2 diabetes from the large TODAY cohort appear to be less physically active and tend to spend more time being sedentary than similarly aged youth without diabetes identified from other large national investigations. Treatment efforts in adolescents with type 2 diabetes should include decreasing sitting along with efforts to increase PA levels.

School-based health promotion and physical activity during and after school hours.

PubMed

Vander Ploeg, Kerry A; McGavock, Jonathan; Maximova, Katerina; Veugelers, Paul J

2014-02-01

Comprehensive school health (CSH) is a multifaceted approach to health promotion. A key objective of CSH is to foster positive health behaviors outside of school. This study examined the 2-year change in physical activity during and after school among students participating in a CSH intervention in Edmonton, Alberta, Canada. This was a quasi-experimental, pre-post trial with a parallel, nonequivalent control group. Intervention schools had to be located in socioeconomically disadvantaged neighborhoods. In the spring of 2009 and 2011, pedometer recordings (7 full days) and demographic data were collected from cross-sectional samples of fifth grade students from 10 intervention schools and 20 comparison schools. A total of 1157 students participated in the study. Analyses were adjusted for potential confounders and the clustered design. Relative to 2009, children in 2011 were more active on schools days (1172 steps per day; P < .001) and on weekends (1450 steps per day; P < .001). However, the increase in mean steps between 2009 and 2011 was greater in CSH intervention schools than in comparison schools (school days: 1221 steps per day; P = .009; weekends: 2001 steps per day; P = .005). These increases remained significant after adjusting for gender and overweight status. These findings provide evidence of the effectiveness of CSH to affect children's physical activity during and outside of school. Results of this study justify broader implementation of effective CSH interventions for physical activity promotion and obesity prevention in the long term.

Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial.

PubMed

Chandra, Alvin; Lewis, Eldrin F; Claggett, Brian L; Desai, Akshay S; Packer, Milton; Zile, Michael R; Swedberg, Karl; Rouleau, Jean L; Shi, Victor C; Lefkowitz, Martin P; Katova, Tzvetana; McMurray, John J V; Solomon, Scott D

2018-04-04

Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ). To examine the effects of sacubitril/valsartan on physical and social activities. The PARADIGM-HF trial was a randomized, double-blind, active treatment-controlled clinical trial performed from December 8, 2009, to March 31, 2014, in 8399 patients with New York Heart Association class II to IV disease and a left ventricular ejection fraction of 40% or less at 1043 centers in 38 countries. Data analysis was performed from August 1, 2017, to December 25, 2017. Sacubitril/valsartan, 200 mg twice daily, or enalapril, 10 mg twice daily. Patients completed HRQL assessments using the KCCQ at randomization, 4-month, 8-month, and annual visits. The effect of sacubitril/valsartan on components of the physical and social limitation sections of the KCCQ at 8 months and longitudinally and related biomarkers and clinical outcomes were studied. At baseline, 7618 of 8399 patients (90.7%) (mean [SD] age, 64 [11] years; 5987 [78.6%] male and 1631 [21.4%] female) completed the initial KCCQ assessment. Patients reported the greatest limitations at baseline in jogging and sexual relationships. Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95% CI, 1.19-3.50; P < .001) and sexual relationships (adjusted change score difference, 2.72; 95% CI, 0.97-4.46; P = .002); both persisted through 36 months (overall change score difference, 1.69 [95% CI, 0.78-2.60], P < .001; and 2.36 [95% CI, 1.01-3.71], P = .001, respectively). In patients with heart failure with reduced ejection fraction, sacubitril/valsartan significantly improved nearly all KCCQ physical and social activities compared with enalapril, with the largest responses in household chores and sexual relationships. In addition to reduced likelihood of cardiovascular death, all-cause mortality, and heart failure hospitalization, sacubitril/valsartan may improve limitations in common activities in these patients. clinicaltrials.gov Identifier: NCT01035255.

Over the counter (OTC) artificial tear drops for dry eye syndrome

PubMed Central

Pucker, Andrew D; Ng, Sueko M; Nichols, Jason J

2016-01-01

Background Over the counter (OTC) artificial tears historically have been the first line of treatment for dry eye syndrome and dry eye-related conditions like contact lens discomfort, yet currently we know little regarding the overall efficacy of individual, commercially available artificial tears. This review provides a much needed meta-analytical look at all randomized and quasi-randomized clinical trials that have analyzed head-to-head comparisons of OTC artificial tears. Objectives To evaluate the effectiveness and toxicity of OTC artificial tear applications in the treatment of dry eye syndrome compared with another class of OTC artificial tears, no treatment, or placebo. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) website (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 4 December 2015. We searched reference lists of included trials for any additional trials not identified by the electronic searches. Selection criteria This review includes randomized controlled trials with adult participants who were diagnosed with dry eye, regardless of race and gender. We included trials in which the age of participants was not reported, and clinical trials comparing OTC artificial tears with another class of OTC artificial tears, placebo, or no treatment. This review did not consider head-to-head comparisons of artificial tears with another type of dry-eye therapy. Data collection and analysis We followed the standard methodological procedures expected by Cochrane. Two authors independently screened the search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. We performed meta-analysis for trials that compared similar interventions and reported comparable outcomes with sufficient data. We summarized all other included trial results in the text. Main results We included 43 randomized controlled trials (3497 participants with dry eye). Due to the heterogeneity of study characteristics among the included trials with respect to types of diagnostic criteria, interventions, comparisons, and measurements taken, our ability to perform meta-analyses was limited. The review found that, in general, there was uncertainty whether different OTC artificial tears provide similar relief of signs and symptoms when compared with each other or placebo. Nevertheless, we found that 0.2% polyacrylic acid-based artificial tears were consistently more effective at treating dry eye symptoms than 1.4% polyvinyl alcohol-based artificial tears in two trials assessing this comparison (175 participants). All other included artificial tears produced contradictory between-group results or found no between-group differences. Our review also found that OTC artificial tears may be generally safe, but not without adverse events. Overall, we assessed the quality of evidence as low due to high risks of bias among included trials and poor reporting of outcome measures which were insufficient for quantitative analysis. Furthermore, we identified an additional 18 potentially eligible trials that were reported only in clinical trial registers with no associated results or publications. These trials reportedly enrolled 2079 total participants for whom no data are available. Such lack of reporting of trial results represents a high risk of publication bias. Authors’ conclusions OTC artificial tears may be safe and effective means for treating dry eye syndrome; the literature indicates that the majority of OTC artificial tears may have similar efficacies. This conclusion could be greatly skewed by the inconsistencies in study designs and inconsistencies in reporting trial results. Additional research is therefore needed before we can draw robust conclusions about the effectiveness of individual OTC artificial tear formulations. PMID:26905373

An n-of-1 trial service in clinical practice: testing the effectiveness of stimulants for attention-deficit/hyperactivity disorder.

PubMed

Nikles, C Jane; Mitchell, Geoffrey K; Del Mar, Chris B; Clavarino, Alexandra; McNairn, Norma

2006-06-01

We sought to describe the clinical use of n-of-1 trials for attention-deficit/hyperactivity disorder in publicly and privately funded family and specialized pediatric practice in Australia. We used a within-patient randomized, double-blind, crossover comparison of stimulant (dexamphetamine or methylphenidate) versus placebo or alternative stimulant using 3 pairs of treatment periods. Trials were conducted from a central location using mail and telephone communication, with local supervision by the patients' clinicians. Our study population included children with clinically diagnosed attention-deficit/hyperactivity disorder who were aged 5 to 16 years and previously stabilized on an optimal dose of stimulant. They were selected because treatment effectiveness was uncertain. Our measures included number of patients recruited, number of doctors who used the service, geographic spread, completion rates, response rate, and post-n-of-1 trial decisions. Forty-five doctors across Australia requested 108 n-of-1 trials, of which 86 were completed. In 69 drug-versus-placebo comparisons, 29 children responded better to stimulant than placebo. Immediately posttrial, 19 of 25 drug-versus-placebo responders stayed on the same stimulant, and 13 of 24 nonresponders ceased or switched stimulants. In 40 of 63 for which data were available, posttrial management was consistent with the trial results. For all types of n-of-1 trials, management changed for 28 of 64 children for whom information was available. Attention-deficit/hyperactivity disorder n-of-1 trials can be implemented successfully by mail and telephone communication. This type of trial can be valuable in clarifying treatment effect when it is uncertain, and in this series, they had a noticeable impact on short-term management.

Anticholinergic versus botulinum toxin A comparison trial for the treatment of bothersome urge urinary incontinence: ABC trial.

PubMed

Visco, Anthony G; Brubaker, Linda; Richter, Holly E; Nygaard, Ingrid; Paraiso, Marie Fidela; Menefee, Shawn A; Schaffer, Joseph; Wei, John; Chai, Toby; Janz, Nancy; Spino, Cathie; Meikle, Susan

2012-01-01

This trial compares the change in urgency urinary incontinence episodes over 6 months, tolerability and cost effectiveness between women receiving daily anticholinergic therapy plus a single intra-detrusor injection of saline versus a single intra-detrusor injection of 100 U of botulinum toxin A plus daily oral placebo tablets. We present the rationale and design of a randomized-controlled trial, Anticholinergic versus Botulinum Toxin, Comparison Trial for the Treatment of Bothersome Urge Urinary Incontinence: ABC trial, conducted by the NICHD-funded Pelvic Floor Disorders Network. We discuss the innovative nature of this trial and the challenges related to choice of patient population, maintaining masking, cost effectiveness, ethical considerations, measuring adherence, and placebo development and testing. Enrollment began in April, 2010. 242 participants will be randomized and primary outcome data analysis is anticipated to begin in mid 2012. Several challenges in the trial design are discussed. Randomization to placebo intra-detrusor injections may limit recruitment, potentially impacting generalizability. Other challenges included the heavy marketing of drugs for overactive bladder which could impact recruitment of drug-naïve women. In addition, anticholinergic medications often cause dry mouth, making masking difficult. Finally, adverse reporting of transient urinary retention is challenging as there is no standardized definition; yet this is the most common adverse event following intra-detrusor botulinum toxin injection. The ABC trial will help women with urgency urinary incontinence balance efficacy, side effects and cost of anticholinergic medication versus botulinum toxin intra-detrusor injection. The results have the potential to fundamentally change the therapeutic approach to this condition. Copyright © 2011 Elsevier Inc. All rights reserved.

Average effect estimates remain similar as evidence evolves from single trials to high-quality bodies of evidence: a meta-epidemiologic study.

PubMed

Gartlehner, Gerald; Dobrescu, Andreea; Evans, Tammeka Swinson; Thaler, Kylie; Nussbaumer, Barbara; Sommer, Isolde; Lohr, Kathleen N

2016-01-01

The objective of our study was to use a diverse sample of medical interventions to assess empirically whether first trials rendered substantially different treatment effect estimates than reliable, high-quality bodies of evidence. We used a meta-epidemiologic study design using 100 randomly selected bodies of evidence from Cochrane reports that had been graded as high quality of evidence. To determine the concordance of effect estimates between first and subsequent trials, we applied both quantitative and qualitative approaches. For quantitative assessment, we used Lin's concordance correlation and calculated z-scores; to determine the magnitude of differences of treatment effects, we calculated standardized mean differences (SMDs) and ratios of relative risks. We determined qualitative concordance based on a two-tiered approach incorporating changes in statistical significance and magnitude of effect. First trials both overestimated and underestimated the true treatment effects in no discernible pattern. Nevertheless, depending on the definition of concordance, effect estimates of first trials were concordant with pooled subsequent studies in at least 33% but up to 50% of comparisons. The pooled magnitude of change as bodies of evidence advanced from single trials to high-quality bodies of evidence was 0.16 SMD [95% confidence interval (CI): 0.12, 0.21]. In 80% of comparisons, the difference in effect estimates was smaller than 0.5 SMDs. In first trials with large treatment effects (>0.5 SMD), however, estimates of effect substantially changed as new evidence accrued (mean change 0.68 SMD; 95% CI: 0.50, 0.86). Results of first trials often change, but the magnitude of change, on average, is small. Exceptions are first trials that present large treatment effects, which often dissipate as new evidence accrues. Copyright © 2016 Elsevier Inc. All rights reserved.

Facilitation of self-transcendence in a breast cancer support group: II.

PubMed

Coward, Doris Dickerson

2003-01-01

To pilot a second support group intervention study promoting self-transcendence perspectives and activities and to document changes over time in well-being in support group participants compared with nonparticipants. Quasiexperimental, partial randomization, preference trial design. An urban breast cancer resource center established by survivors. 41 women with newly diagnosed breast cancer were recruited, and 39 completed the study. 22 women participated in three intervention support groups; 17 were in a comparison group. The intervention was an eight-week, closed support group based on self-transcendence theory. Data were collected three times during 14 months. Support group intervention, self-transcendence, and emotional and physical well-being. The intervention group had lower scores than the comparison group on self-transcendence and well-being variables at baseline (time [T] 1). Scores were higher for both groups postintervention (T2), with no differences between groups. One year postintervention (T3), intervention group scores again were lower than comparison group scores. Intervention group T3 scores were unchanged from T2. Most potential participants were unwilling to risk being randomized into a nonpreferred group. Activities based on self-transcendence theory were associated with expanded perspectives and activities and an improved sense of well-being in support group participants at the end of the intervention, but not one year later. Findings from the pilot studies informed a study currently in progress. Nurses should maintain awareness of local resources for support and make that information available to women when they are newly diagnosed with breast cancer, during their treatment, and later.

Cold-water immersion (cryotherapy) for preventing and treating muscle soreness after exercise.

PubMed

Bleakley, Chris; McDonough, Suzanne; Gardner, Evie; Baxter, G David; Hopkins, J Ty; Davison, Gareth W

2012-02-15

Many strategies are in use with the intention of preventing or minimising delayed onset muscle soreness and fatigue after exercise. Cold-water immersion, in water temperatures of less than 15°C, is currently one of the most popular interventional strategies used after exercise. To determine the effects of cold-water immersion in the management of muscle soreness after exercise. In February 2010, we searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library (2010, Issue 1), MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health (CINAHL), British Nursing Index and archive (BNI), and the Physiotherapy Evidence Database (PEDro). We also searched the reference lists of articles, handsearched journals and conference proceedings and contacted experts.In November 2011, we updated the searches of CENTRAL (2011, Issue 4), MEDLINE (up to November Week 3 2011), EMBASE (to 2011 Week 46) and CINAHL (to 28 November 2011) to check for more recent publications. Randomised and quasi-randomised trials comparing the effect of using cold-water immersion after exercise with: passive intervention (rest/no intervention), contrast immersion, warm-water immersion, active recovery, compression, or a different duration/dosage of cold-water immersion. Primary outcomes were pain (muscle soreness) or tenderness (pain on palpation), and subjective recovery (return to previous activities without signs or symptoms). Three authors independently evaluated study quality and extracted data. Some of the data were obtained following author correspondence or extracted from graphs in the trial reports. Where possible, data were pooled using the fixed-effect model. Seventeen small trials were included, involving a total of 366 participants. Study quality was low. The temperature, duration and frequency of cold-water immersion varied between the different trials as did the exercises and settings. The majority of studies failed to report active surveillance of pre-defined adverse events.Fourteen studies compared cold-water immersion with passive intervention. Pooled results for muscle soreness showed statistically significant effects in favour of cold-water immersion after exercise at 24 hour (standardised mean difference (SMD) -0.55, 95% CI -0.84 to -0.27; 10 trials), 48 hour (SMD -0.66, 95% CI -0.97 to -0.35; 8 trials), 72 hour (SMD -0.93; 95% CI -1.36 to -0.51; 4 trials) and 96 hour (SMD -0.58; 95% CI -1.00 to -0.16; 5 trials) follow-ups. These results were heterogeneous. Exploratory subgroup analyses showed that studies using cross-over designs or running based exercises showed significantly larger effects in favour of cold-water immersion. Pooled results from two studies found cold-water immersion groups had significantly lower ratings of fatigue (MD -1.70; 95% CI -2.49 to -0.90; 10 units scale, best to worst), and potentially improved ratings of physical recovery (MD 0.97; 95% CI -0.10 to 2.05; 10 units scale, worst to best) immediately after the end of cold-water immersion.Five studies compared cold-water with contrast immersion. Pooled data for pain showed no evidence of differences between the two groups at four follow-up times (immediately, 24, 48 and 72 hours after treatment). Similar findings for pooled analyses at 24, 48 and 72 hour follow-ups applied to the four studies comparing cold-water with warm-water immersion. Single trials only compared cold-water immersion with respectively active recovery, compression and a second dose of cold-water immersion at 24 hours. There was some evidence that cold-water immersion reduces delayed onset muscle soreness after exercise compared with passive interventions involving rest or no intervention. There was insufficient evidence to conclude on other outcomes or for other comparisons. The majority of trials did not undertake active surveillance of pre-defined adverse events. High quality, well reported research in this area is required.

Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials

PubMed Central

Papandonatos, George D.; Pan, Qing; Pajewski, Nicholas M.; Delahanty, Linda M.; Peter, Inga; Erar, Bahar; Ahmad, Shafqat; Harden, Maegan; Chen, Ling; Fontanillas, Pierre; Wagenknecht, Lynne E.; Kahn, Steven E.; Wing, Rena R.; Jablonski, Kathleen A.; Huggins, Gordon S.; Knowler, William C.; Florez, Jose C.

2015-01-01

Clinically relevant weight loss is achievable through lifestyle modification, but unintentional weight regain is common. We investigated whether recently discovered genetic variants affect weight loss and/or weight regain during behavioral intervention. Participants at high-risk of type 2 diabetes (Diabetes Prevention Program [DPP]; N = 917/907 intervention/comparison) or with type 2 diabetes (Look AHEAD [Action for Health in Diabetes]; N = 2,014/1,892 intervention/comparison) were from two parallel arm (lifestyle vs. comparison) randomized controlled trials. The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2–4 after a minimum of 3% weight loss were tested. Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD. No such effect was observed across comparison arms, leading to a nominally significant single nucleotide polymorphism×treatment interaction (P = 4.3 × 10−3). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 × 10−4). Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials, directly or via interactions with lifestyle. PMID:26253612

Effect of home-based counselling on newborn care practices in southern Tanzania one year after implementation: a cluster-randomised controlled trial

PubMed Central

2014-01-01

Background In Sub-Saharan Africa over one million newborns die annually. We developed a sustainable and scalable home-based counselling intervention for delivery by community volunteers in rural southern Tanzania to improve newborn care practices and survival. Here we report the effect on newborn care practices one year after full implementation. Methods All 132 wards in the 6-district study area were randomised to intervention or comparison groups. Starting in 2010, in intervention areas trained volunteers made home visits during pregnancy and after childbirth to promote recommended newborn care practices including hygiene, breastfeeding and identification and extra care for low birth weight babies. In 2011, in a representative sample of 5,240 households, we asked women who had given birth in the previous year both about counselling visits and their childbirth and newborn care practices. Results Four of 14 newborn care practices were more commonly reported in intervention than comparison areas: delaying the baby’s first bath by at least six hours (81% versus 68%, OR 2.0 (95% CI 1.2-3.4)), exclusive breastfeeding in the three days after birth (83% versus 71%, OR 1.9 (95% CI 1.3-2.9)), putting nothing on the cord (87% versus 70%, OR 2.8 (95% CI 1.7-4.6)), and, for home births, tying the cord with a clean thread (69% versus 39%, OR 3.4 (95% CI 1.5-7.5)). For other behaviours there was little evidence of differences in reported practices between intervention and comparison areas including childbirth in a health facility or with a skilled attendant, thermal care practices, breastfeeding within an hour of birth and, for home births, the birth attendant having clean hands, cutting the cord with a clean blade and birth preparedness activities. Conclusions A home-based counselling strategy using volunteers and designed for scale-up can improve newborn care behaviours in rural communities of southern Tanzania. Further research is needed to evaluate if, and at what cost, these gains will lead to improved newborn survival. Trial registration Trial Registration Number NCT01022788 (http://www.clinicaltrials.gov, 2009) PMID:25052850

A clinical evaluation of a remote mobility monitoring system based on SMS messaging.

PubMed

Dalton, Anthony F; Ní Scanaill, Cliodhna; Carew, Sheila; Lyons, Declan; OLaighin, Gearóid

2007-01-01

The objective of this work was to evaluate the accuracy and viability of a mobility telemonitoring system, based on the short message service (SMS), to monitor the functional mobility of elderly subjects in an unsupervised environment. A clinical trial was conducted consisting of 6 elderly subjects; 3 male, 3 female (mean: 81.7, SD: 5.09). Mobility was monitored using an accelerometer based portable unit worn by each monitored subject for eleven hours. Every 15 minutes the mobility of the subject was summarized and transmitted as an SMS message from the portable unit to a remote server for long term analysis. The activPAL Trio Professional physical activity logger was simultaneously used for comparison with the portable unit. On conclusion of the trial each subject completed a questionnaire detailing their satisfaction with the portable unit and any recommendations for improvements. Overall a percentage difference of 2.31% was found between the activPAL Trio and the portable unit for the detection of sitting. For the combined postures of standing and walking the percentage difference was calculated as 2.9%. A bivariate correlation and regression analysis was performed on the entire data set of one subject. Strong positive correlation's were found for the detection of sitting (r = 0.996) and for the combined postures of standing and walking (r = 0.994). Subjects suggested that a lighter, smaller and wireless unit would be more effective.

Neural correlates of high-gamma oscillations (60–200 Hz) in macaque local field potentials and their potential implications in electrocorticography

PubMed Central

Crone, Nathan E.; Niebur, Ernst; Franaszczuk, Piotr J.; Hsiao, Steven S.

2009-01-01

Recent studies using electrocorticographic (ECoG) recordings in humans have shown that functional activation of cortex is associated with an increase in power in the high-gamma frequency range (∼60–200 Hz). Here we investigate the neural correlates of this high-gamma activity in local field potential (LFP). Single units and LFP were recorded with microelectrodes from the hand region of macaque SII cortex while vibrotactile stimuli of varying intensities were presented to the hand. We found that high-gamma power in the LFP was strongly correlated with the average firing rate recorded by the microelectrodes, both temporally and on a trial-by-trial basis. In comparison, the correlation between firing rate and low-gamma power (40–80 Hz) was much smaller. In order to explore the potential effects of neuronal firing on ECoG, we developed a model to estimate ECoG power generated by different firing patterns of the underlying cortical population and studied how ECoG power varies with changes in firing rate versus the degree of synchronous firing between neurons in the population. Both an increase in firing rate and neuronal synchrony increased high-gamma power in the simulated ECoG data. However, ECoG high-gamma activity was much more sensitive to increases in neuronal synchrony than firing rate. PMID:18987189

Therapeutic Uses of Active Videogames: A Systematic Review.

PubMed

Staiano, Amanda E; Flynn, Rachel

2014-12-01

Active videogames (AVGs) may be useful for promoting physical activity for therapeutic uses, including for balance, rehabilitation, and management of illness or disease. The literature from 64 peer-reviewed publications that assessed health outcomes of AVGs for therapeutic purposes was synthesized. PubMed, Medline, and PyschInfo were queried for original studies related to the use of AVGs to improve physical outcomes in patients who were ill or undergoing rehabilitation related to balance, burn treatment, cancer, cerebral palsy, Down's syndrome, extremity dysfunction or amputation, hospitalization, lupus, Parkinson's disease, spinal injury, or stroke. The following inclusion criteria were used: (1) human subjects; (2) English language; (3) not duplicates; (4) new empirical data; and (5) tests an AVG, including commercially available or custom-designed. Studies were included regardless of participants' age or the study design. Overall, the vast majority of studies demonstrated promising results for improved health outcomes related to therapy, including significantly greater or comparable effects of AVG play versus usual care. However, many studies were pilot trials with small, homogeneous samples, and many studies lacked a control or comparison group. Some trials tested multiweek or multimonth interventions, although many used a single bout of gameplay, and few included follow-up assessments to test sustainability of improved health. AVGs were acceptable and enjoyable to the populations examined and appear as a promising tool for balance, rehabilitation, and illness management. Future research directions and implications for clinicians are discussed.

It's all about kids: preventing overweight in elementary school children in Tulsa, OK.

PubMed

DeVault, Norma; Kennedy, Tay; Hermann, Janice; Mwavita, Mwarumba; Rask, Pam; Jaworsky, Amber

2009-04-01

In response to the increased incidence of child overweight, a school-based program, It's All About Kids, was designed by the Tulsa Health Department, Tulsa Public Schools, and community partners to improve food choices and increase physical activity of students in first through fifth grade. The nutrition component consisted of six weekly 30-minute experiential, age-appropriate classroom lessons, including healthful-eating food games, taste-testing foods, whole-grain bread baking, information on portion sizes, and food demonstrations. Documenting and evaluating school-based intervention programs is critical for setting evidence-based health policy, justifying funding, and achieving broader implementation of successful interventions. To evaluate the effectiveness of the It's All About Kids nutrition component in fourth-grade children, we conducted a controlled trial from 20 fourth-grade classes in five intervention and five comparison Title I public schools. Evaluation included 140 fourth-grade students, including 69 in the comparison group and 71 in the intervention group. Outcomes were measured by pre-, post-, and follow-up tests using a modified version of the Pathways Knowledge, Attitudes, and Behaviors questionnaire and the Child and Adolescent Trial of Cardiovascular Health (CATCH) Food Checklist. Data were analyzed using repeated measures analysis of variance over time controlling for sex, paired samples t tests, and independent samples t tests. Intervention students had significant improvements in knowledge of which food had more fat (P<0.043). Intervention students' behavioral intent scale scores for food choice intentions improved significantly (P<0.014). Self-reported consumption of saturated fat and sodium improved considerably in both intervention and comparison students. We conclude that results support a broader program implementation. More reinforcement over time may be needed to sustain the level of improvement.

Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn's disease and ulcerative colitis.

PubMed

Mao, E J; Hazlewood, G S; Kaplan, G G; Peyrin-Biroulet, L; Ananthakrishnan, A N

2017-01-01

Crohn's disease (CD) and ulcerative colitis (UC) have a progressive course leading to hospitalisation and surgery. The ability of existing therapies to alter disease course is not clearly defined. To investigate the comparative efficacy of currently available inflammatory bowel disease (IBD) therapies to reduce hospitalisation and surgery. We conducted a systematic review in MEDLINE/PubMed for randomised controlled trials (RCT) published between January 1980 and May 2016 examining efficacy of biological or immunomodulator therapy in IBD. We performed direct comparisons of pooled proportions of hospitalisation and surgery. Pair-wise comparisons using a random-effects Bayesian network meta-analysis were performed to assess comparative efficacy of different treatments. We identified seven randomised controlled trials (5 CD; 2 UC) comparing three biologics and one immunomodulator with placebo. In CD, anti-TNF biologics significantly reduced hospitalisation [Odds ratio (OR) 0.46, 95% confidence interval (CI) 0.36-0.60] and surgery (OR 0.23, 95% CI 0.13-0.42) compared to placebo. No statistically significant reduction was noted with azathioprine or vedolizumab. Azathioprine was inferior to both infliximab and adalimumab in preventing CD-related hospitalisation (>97.5% probability). Anti-TNF biologics significantly reduced hospitalisation (OR 0.48, 95% CI 0.29-0.80) and surgery (OR 0.67, 95% CI 0.46-0.97) in UC. There were no statistically significant differences in the pair-wise comparisons between active treatments. In CD and UC, anti-TNF biologics are efficacious in reducing the odds of hospitalisation by half and surgery by 33-77%. Azathioprine and vedolizumab were not associated with a similar improvement, but robust conclusions may be limited due to paucity of RCTs. © 2016 John Wiley & Sons Ltd.

Surgical interventions for treating acute fractures or non-union of the middle third of the clavicle.

PubMed

Lenza, Mário; Faloppa, Flávio

2015-05-07

This review covers two conditions: acute clavicle fractures and non-union resulting from failed fracture healing. Clavicle (collarbone) fractures account for around 4% of all fractures. While treatment for these fractures is usually non-surgical, some types of clavicular fractures, as well as non-union of the middle third of the clavicle, are often treated surgically. This is an update of a Cochrane review first published in 2009. To evaluate the effects (benefits and harms) of different methods of surgical treatment for acute fracture or non-union of the middle third of the clavicle. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (27 June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 5), MEDLINE (1966 to June week 3 2014), EMBASE (1988 to 2014 week 25), LILACS (1982 to 27 June 2014), trial registries and reference lists of articles. We applied no language or publication restrictions. We considered randomised and quasi-randomised controlled trials evaluating any surgical intervention for treating people with fractures or non-union of the middle third of the clavicle. The primary outcomes were shoulder function or disability, pain and treatment failure (measured by the number of participants who had undergone or were being considered for a non-routine secondary surgical intervention for symptomatic non-union, malunion or other complications). Two review authors selected eligible trials, independently assessed risk of bias and cross-checked data. Where appropriate, we pooled results of comparable trials. We included seven trials in this review with 398 participants. Four trials were new in this update.The four new trials (160 participants) compared intramedullary fixation with open reduction and internal fixation with plate for treating acute middle third clavicle fractures in adults. Low quality evidence from the four trials indicated that intramedullary fixation did not result in a clinically important improvement in upper arm function (despite a statistically significant difference in its favour: standardised mean difference 0.45, 95% confidence interval (CI) 0.08 to 0.81; 120 participants, three trials) at long term follow-up of six months or more. Very low quality evidence indicated little difference between intramedullary fixation and plate fixation in pain (one trial), treatment failure resulting in non-routine surgery (2/68 with intramedullary fixation vs. 3/65 with plate fixation; risk ratio 0.69, 95% CI 0.16 to 2.97, four trials) or time to clinical fracture consolidation (three trials). There was very low quality evidence of a lower incidence of participants with adverse events (mainly infection, poor cosmetic result and symptomatic hardware) in the intramedullary fixation group (18/68 with intramedullary fixation vs. 27/65 with plate fixation; RR 0.64, 95% CI 0.39 to 1.03) but the CI of the pooled results also included the small possibility of a lower incidence in the plate fixation group. None of the four trials reported on quality of life or return to previous activities. Evidence is pending from two ongoing trials, with planned recruitment of 245 participants, testing this comparison.There was low or very low quality evidence from three small trials, each testing a different comparison. The three trials had design features that carried a high risk of bias, potentially limiting the reliability of their findings. Low-contact dynamic compression plates appeared to be associated with significantly better upper-limb function throughout the year following surgery, earlier fracture union and return to work, and a reduced incidence of implant-associated symptoms when compared with a standard dynamic compression plate in 36 adults with symptomatic non-union of the middle third of the clavicle. One quasi-randomised trial (69 participants) compared Knowles pin versus a plate for treating middle third clavicle fractures or non-union. Knowles pins appeared to be associated with lower pain levels and use of postoperative analgesics and a reduced incidence of implant-associated symptoms. One study (133 participants) found that a three-dimensional technique for fixation with a reconstruction plate was associated with a significantly lower incidence of symptomatic delayed union than a standard superior position surgical approach. Evidence is pending from two ongoing trials, with planned recruitment of 130 participants, comparing anterior versus superior plates for acute fractures. There is very limited and low quality evidence available from randomised controlled trials regarding the effectiveness of different methods of surgical fixation of fractures and non-union of the middle third of the clavicle. The evidence from four ongoing trials is likely to inform practice for the comparisons of intramedullary versus plate fixation and anterior versus superior plates for acute fractures in a future update. Further randomised trials are warranted, but in order to optimise research effort, these should be preceded by research that aims to identify priority questions.

A methodology for assessing the effect of correlations among muscle synergy activations on task-discriminating information.

PubMed

Delis, Ioannis; Berret, Bastien; Pozzo, Thierry; Panzeri, Stefano

2013-01-01

Muscle synergies have been hypothesized to be the building blocks used by the central nervous system to generate movement. According to this hypothesis, the accomplishment of various motor tasks relies on the ability of the motor system to recruit a small set of synergies on a single-trial basis and combine them in a task-dependent manner. It is conceivable that this requires a fine tuning of the trial-to-trial relationships between the synergy activations. Here we develop an analytical methodology to address the nature and functional role of trial-to-trial correlations between synergy activations, which is designed to help to better understand how these correlations may contribute to generating appropriate motor behavior. The algorithm we propose first divides correlations between muscle synergies into types (noise correlations, quantifying the trial-to-trial covariations of synergy activations at fixed task, and signal correlations, quantifying the similarity of task tuning of the trial-averaged activation coefficients of different synergies), and then uses single-trial methods (task-decoding and information theory) to quantify their overall effect on the task-discriminating information carried by muscle synergy activations. We apply the method to both synchronous and time-varying synergies and exemplify it on electromyographic data recorded during performance of reaching movements in different directions. Our method reveals the robust presence of information-enhancing patterns of signal and noise correlations among pairs of synchronous synergies, and shows that they enhance by 9-15% (depending on the set of tasks) the task-discriminating information provided by the synergy decompositions. We suggest that the proposed methodology could be useful for assessing whether single-trial activations of one synergy depend on activations of other synergies and quantifying the effect of such dependences on the task-to-task differences in muscle activation patterns.

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

PubMed

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

2018-03-27

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

Reducing neuropsychiatric symptoms in persons with dementia and associated burden in family caregivers using tailored activities: Design and methods of a randomized clinical trial

PubMed Central

Gitlin, Laura N.; Piersol, Catherine Verrier; Hodgson, Nancy; Marx, Katherine; Roth, David L.; Johnson, Deidre; Samus, Quincy; Pizzi, Laura; Jutkowitz, Eric; Lyketsos, Constantine G.

2016-01-01

Among over 5 million people in the USA with dementia, neuropsychiatric symptoms (NPS) are almost universal, occurring across disease etiology and stage. If untreated, NPS can lead to significant morbidity and mortality including increased cost, distress, depression, and faster disease progression, as well as heightened burden on families. With few pharmacological solutions, , identifying nonpharmacologic strategies is critical. We describe a randomized clinical trial, the Dementia Behavior Study, to test the efficacy of an activity program to reduce significant existing NPS and associated caregiver burden at 3 and 6 months compared to a control group intervention. Occupational therapists deliver 8 in-home sessions over 3 months to assess capabilities and interests of persons with dementia, home environments, and caregiver knowledge, and readiness from which activities are developed and families trained in their use. Families learn to modify activities for future declines and use strategies to address care challenges. The comparison group controls for time and attention and involves 8 in-home sessions delivered by health educators who provide dementia education, home safety recommendations, and advanced care planning. We are randomizing 250 racially diverse families (person with dementia and primary caregiver dyads) recruited from community-based social services, conferences and media announcements. The primary outcome is change in agitation/aggression at 3 and 6 months. Secondary outcomes assess quality of life of persons with dementia, other behaviors, burden and confidence of caregivers, and cost effectiveness. If benefits are supported, this activity intervention will provide a clinically meaningful approach to prevent, reduce, and manage NPS. PMID:27339865

You Are the Danger: Attenuated Insula Response in Methamphetamine Users During Aversive Interoceptive Decision-Making*

PubMed Central

Stewart, Jennifer L.; May, April C.; Poppa, Tasha; Davenport, Paul W.; Tapert, Susan F.; Paulus, Martin P.

2014-01-01

Background Drug dependent individuals often make drug-taking decisions when they do not feel well. Yet, few studies have examined the influence of an aversive state on decision-making related neural processing. Methods We investigate brain activation to decision-making during an aversive interoceptive challenge in methamphetamine users using functional magnetic resonance imaging (fMRI). Recently abstinent inpatients with methamphetamine use disorder (METH; n=20) and healthy comparison subjects (CTL; n=22) performed a two-choice prediction task at three fixed error rates (ER; 20%=reward, 50%=uncertainty, 80%=punishment) while anticipating and experiencing episodes of inspiratory breathing load during fMRI. Results METH exhibited higher trait anxiety in conjunction with lower anterior insula (AI) and inferior frontal gyrus (IFG) activation than CTL across trials. METH also showed lower posterior insula (PI) and anterior cingulate cortex (ACC) activation than CTL during breathing load independent of ER. For the crucial ER by interoception interaction, METH displayed lower ACC activation to punishment/loss than CTL during breathing load. Within METH, lower trait anxiety was linked to bilateral AI/IFG attenuation across trials. Conclusions AI/IFG attenuations in METH are suggestive of an executive functioning deficit, particularly in users with low anxiety, reflecting reduced resources allocated to choice selection. In contrast, PI/ACC reductions in METH appear specific to impairments in registering and evaluating interoceptive experiences. Taken together, inadequate activation of brain areas that are important for regulating when one does not feel well may be the neural basis for poor decision-making by METH. PMID:24993186

Physically Active Math and Language Lessons Improve Academic Achievement: A Cluster Randomized Controlled Trial.

PubMed

Mullender-Wijnsma, Marijke J; Hartman, Esther; de Greeff, Johannes W; Doolaard, Simone; Bosker, Roel J; Visscher, Chris

2016-03-01

Using physical activity in the teaching of academic lessons is a new way of learning. The aim of this study was to investigate the effects of an innovative physically active academic intervention ("Fit & Vaardig op School" [F&V]) on academic achievement of children. Using physical activity to teach math and spelling lessons was studied in a cluster-randomized controlled trial. Participants were 499 children (mean age 8.1 years) from second- and third-grade classes of 12 elementary schools. At each school, a second- and third-grade class were randomly assigned to the intervention or control group. The intervention group participated in F&V lessons for 2 years, 22 weeks per year, 3 times a week. The control group participated in regular classroom lessons. Children's academic achievement was measured before the intervention started and after the first and second intervention years. Academic achievement was measured by 2 mathematics tests (speed and general math skills) and 2 language tests (reading and spelling). After 2 years, multilevel analysis showed that children in the intervention group had significantly greater gains in mathematics speed test (P < .001; effect size [ES] 0.51), general mathematics (P < .001; ES 0.42), and spelling (P < .001; ES 0.45) scores. This equates to 4 months more learning gains in comparison with the control group. No differences were found on the reading test. Physically active academic lessons significantly improved mathematics and spelling performance of elementary school children and are therefore a promising new way of teaching. Copyright © 2016 by the American Academy of Pediatrics.

Benefits and problems of health-care robots in aged care settings: A comparison trial.

PubMed

Broadbent, Elizabeth; Kerse, Ngaire; Peri, Kathryn; Robinson, Hayley; Jayawardena, Chandimal; Kuo, Tony; Datta, Chandan; Stafford, Rebecca; Butler, Haley; Jawalkar, Pratyusha; Amor, Maddy; Robins, Ben; MacDonald, Bruce

2016-03-01

This study investigated whether multiple health-care robots could have any benefits or cause any problems in an aged care facility. Fifty-three residents and 53 staff participated in a non-randomised controlled trial over 12 weeks. Six robots provided entertainment, communication and health-monitoring functions in staff rooms and activity lounges. These settings were compared to control settings without robots. There were no significant differences between groups in resident or staff outcomes, except a significant increase in job satisfaction in the control group only. The intervention group perceived the robots had more agency and experience than the control group did. Perceived agency of the robots decreased over time in both groups. Overall, we received very mixed responses with positive, neutral and negative comments. The robots had no major benefits or problems. Future research could give robots stronger operational roles, use more specific outcome measures, and perform cost-benefit analyses. © 2015 AJA Inc.

[Ambulatory laparoscopic cholecystectomy by minilaparoscopy versus traditional multiport ambulatory laparoscopic cholecystectomy. Prospective randomized trial].

PubMed

Planells Roig, Manuel; Arnal Bertomeu, Consuelo; Garcia Espinosa, Rafael; Cervera Delgado, Maria; Carrau Giner, Miguel

2016-02-01

Difference analysis of ambulatorization rate, pain, analgesic requirements and daily activities recovery in patients undergoing laparoscopic cholecystectomy with standard multiport access (CLMP) versus a minilaparoscopic, 3mm size, technique. Prospective randomized trial of 40 consecutive patients undergoing laparoscopic cholecystectomy. Comparison criteria included predictive ultrasound factors of difficult cholecystectomy, previous history of complicated biliary disease and demographics. Results are analyzed in terms of ambulatorization rate, pain, analgesic requirements, postoperative recovery, technical difficulty, hemorrhage intensity, overnight stay, readmission rate and total or partial conversion. Both procedures were similar in surgery time, technical score and hemorrhage score. MLC was associated with similar ambulatorization rate, 85%, and over-night stay 15%, with only 15% partial conversion rate. MLC showed less postoperative pain (P=.026), less analgesic consumption (P=.006) and similar DAR (P=.879). MLC is similar to CLMP in terms of ambulatorization with less postoperative pain and analgesic requirements without differences in postoperative recovery. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Bilingualism influences inhibitory control in auditory comprehension

PubMed Central

Blumenfeld, Henrike K.; Marian, Viorica

2013-01-01

Bilinguals have been shown to outperform monolinguals at suppressing task-irrelevant information. The present study aimed to identify how processing linguistic ambiguity during auditory comprehension may be associated with inhibitory control. Monolinguals and bilinguals listened to words in their native language (English) and identified them among four pictures while their eye-movements were tracked. Each target picture (e.g., hamper) appeared together with a similar-sounding within-language competitor picture (e.g., hammer) and two neutral pictures. Following each eye-tracking trial, priming probe trials indexed residual activation of target words, and residual inhibition of competitor words. Eye-tracking showed similar within-language competition across groups; priming showed stronger competitor inhibition in monolinguals than in bilinguals, suggesting differences in how inhibitory control was used to resolve within-language competition. Notably, correlation analyses revealed that inhibition performance on a nonlinguistic Stroop task was related to linguistic competition resolution in bilinguals but not in monolinguals. Together, monolingual-bilingual comparisons suggest that cognitive control mechanisms can be shaped by linguistic experience. PMID:21159332

A comparison of healing rates on two pressure-relieving systems.

PubMed

Russell, L; Reynolds, T; Carr, J; Evans, A; Holmes, M

The authors have previously reported the preliminary results of a randomized-controlled trial comparing the relative efficacy of two pressure-relieving systems: Huntleigh Nimbus 3 and Aura Cushion, and Pegasus Cairwave Therapy System and ProActive Seating Cushion (Russell et al, 2000). Although both the mattresses and cushions were effective treatments for pressure ulcers, the Huntleigh equipment was demonstrated to be statistically more effective for heel ulcers, but no differences were demonstrated for sacral ulcers. This article gives a more detailed analysis of the 141 patients assessed using computerized-image analysis of the digital images of sacral ulcers captured during the trial and specifically discusses the healing rates and other patient characteristics. Ninety-eight per cent of ulcers examined were deemed superficial (Torrance grade 2a, 2b, 3). Precision of image analysis assessed by within- and between-batch coefficients of variation was excellent: calibration CV 0.93-1.84%; area CV 4.61-5.72%. The healing rates on the two mattresses were not shown to be statistically different from each other.

Comparison of Iontophoretic Lidocaine to EMLA Cream for Pain Reduction Prior to Intravenous Cannulation in Adults

DTIC Science & Technology

2000-10-01

Arvidsson, S.B., Ekroth, R.H., Hansby, M.C., Lindholm, A.H., & William- Olsson, G. (1984). Painless venipuncture. A clinical trial of iontophoresis of...T.J., & Hennes, H.M. (1999). A randomized clinical trial of dermal anesthesia by iontophoresis for peripheral intravenous catheter placement in...Health and Human Services. Brown, B.W.Jr. (1980). The crossover experiment for clinical trials . Biometrics, 36, 69-79. Burns, N., & Grove, S.K. (1997). The

Comparison of Iontophoretic Lidocaine to EMLA Cream for Pain Reduction Prior to Intravenous Fannulation in Adults

DTIC Science & Technology

2000-10-01

Medicine, 62, 989-993. Arvidsson, S.B., Ekroth, R.H., Hansby, M.C., Lindholm, A.H., & William- Olsson, G. (1984). Painless venipuncture. A clinical trial of...N.M., Troshynski, T.J., & Hennes, H.M. (1999). A randomized clinical trial of dermal anesthesia by iontophoresis for peripheral intravenous catheter...Department of Health and Human Services. Brown, B.W.Jr. (1980). The crossover experiment for clinical trials . Biometrics, 36, 69-79. Burns, N

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

PubMed Central

2010-01-01

Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676 PMID:20398378

Delayed temporal discrimination in pigeons: A comparison of two procedures

PubMed Central

Chatlosh, Diane L.; Wasserman, Edward A.

1987-01-01

A within-subjects comparison was made of pigeons' performance on two temporal discrimination procedures that were signaled by differently colored keylight samples. During stimulus trials, a peck on the key displaying a slanted line was reinforced following short keylight samples, and a peck on the key displaying a horizontal line was reinforced following long keylight samples, regardless of the location of the stimuli on those two choice keys. During position trials, a peck on the left key was reinforced following short keylight samples and a peck on the right key was reinforced following long keylight samples, regardless of which line stimulus appeared on the correct key. Thus, on stimulus trials, the correct choice key could not be discriminated prior to the presentation of the test stimuli, whereas on position trials, the correct choice key could be discriminated during the presentation of the sample stimulus. During Phase 1, with a 0-s delay between sample and choice stimuli, discrimination learning was faster on position trials than on stimulus trials for all 4 birds. During Phase 2, 0-, 0.5-, and 1.0-s delays produced differential loss of stimulus control under the two tasks for 2 birds. Response patterns during the delay intervals provided some evidence for differential mediation of the two delayed discriminations. These between-task differences suggest that the same processes may not mediate performance in each. PMID:16812483

From comparison to classification: a cortical tool for boosting perception.

PubMed

Nahum, Mor; Daikhin, Luba; Lubin, Yedida; Cohen, Yamit; Ahissar, Merav

2010-01-20

Humans are much better in relative than in absolute judgments. This common assertion is based on findings that discrimination thresholds are much lower when measured with methods that allow interstimuli comparisons than when measured with methods that require classification of one stimulus at a time and are hence sensitive to memory load. We now challenged this notion by measuring discrimination thresholds and evoked potentials while listeners performed a two-tone frequency discrimination task. We tested various protocols that differed in the pattern of cross-trial tone repetition. We found that best performance was achieved only when listeners effectively used cross-trial repetition to avoid interstimulus comparisons with the repeated reference tone. Instead, they classified one tone, the nonreference tone, as either high or low by comparing it with a recently formed internal reference. Listeners were not aware of the switch from interstimulus comparison to classification. Its successful use was revealed by the conjunction of improved behavioral performance and an event-related potential component (P3), indicating an implicit perceptual decision, which followed the nonreference tone in each trial. Interestingly, tone repetition itself did not suffice for the switch, implying that the bottleneck to discrimination does not reside at the lower, sensory stage. Rather, the temporal consistency of repetition was important, suggesting the involvement of higher-level mechanisms with longer time constants. These findings suggest that classification is based on more automatic and accurate mechanisms than interstimulus comparisons and that the ability to effectively use them depends on a dynamic interplay between higher- and lower-level cortical mechanisms.

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

Hehenkamp, Wouter J.K.; Volkers, Nicole A.; Birnie, Erwin

Purpose. To evaluate the safety and efficacy of uterine artery embolization (UAE) and hysterectomy for symptomatic uterine fibroids by means of a randomized controlled trial. The present paper analyses short-term outcomes, i.e., pain and return to daily activities. Methods. Patients were randomized (1:1) to UAE or hysterectomy. Pain was assessed during admission and after discharge, both quantitatively and qualitatively, using a numerical rating scale and questionnaires. Time to return to daily activities was assessed by questionnaire. Results. Seventy-five patients underwent hysterectomy and 81 patients underwent UAE. UAE patients experienced significantly less pain during the first 24 hr after treatment (pmore » = 0.012). Non-white patients had significantly higher pain scores. UAE patients returned significantly sooner to daily activities than hysterectomy patients (for paid work: 28.1 versus 63.4 days; p < 0.001). In conclusion, pain appears to be less after UAE during hospital stay. Return to several daily activities was in favor of UAE in comparison with hysterectomy.« less

Anti-inflammatory activity of Shirishavaleha: An Ayurvedic compound formulation

PubMed Central

Yadav, Shyamlal Singh; Galib; Ravishankar, B.; Prajapati, P.K.; Ashok, B.K.; Varun, B.

2010-01-01

The purpose of the present study was to evaluate the anti-inflammatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth.), viz. the bark (Twak) and the heartwood (Sara). The activity was screened in the carrageenan-induced rat paw edema model in albino rats. The raw materials were collected and authenticated in the university and the trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for 5 days. Phenylbutazone was used as the standard anti-inflammatory drug for comparison. Between the two different test samples studied, the formulation made from heartwood showed a weak anti-inflammatory activity in this model while that made from the bark produced a considerable suppression of edema after 6 h. It appears that the bark sample would be preferable for clinical use. PMID:21455445

Testing Unsuccessfully: A Specification of the Underlying Mechanisms Supporting Its Influence on Retention

ERIC Educational Resources Information Center

Knight, Justin B.; Ball, B. Hunter; Brewer, Gene A.; DeWitt, Michael R.; Marsh, Richard L.

2012-01-01

Five experiments were conducted to examine how unsuccessful retrieval influences learning and subsequent memory. We used a cued-recall paradigm that produces many unsuccessful retrieval attempts (followed by feedback) and allows comparisons to be made between later memory for these trials and trials that only required reading or studying the…

A Warning Intervention Improves Students' Ability to Overcome Intuitive Interference

ERIC Educational Resources Information Center

Babai, Reuven; Shalev, Enav; Stavy, Ruth

2015-01-01

Students' difficulties in mathematics and science may stem from interference of the task's salient irrelevant variables. Here, we focus on a comparison of perimeters task, in which the area is the irrelevant salient variable. In congruent trials (no interference), accuracy is higher and reaction time is shorter than in incongruent trials (area…

A Comparison of Error-Correction Procedures on Skill Acquisition during Discrete-Trial Instruction

ERIC Educational Resources Information Center

Carroll, Regina A.; Joachim, Brad T.; St. Peter, Claire C.; Robinson, Nicole

2015-01-01

Previous research supports the use of a variety of error-correction procedures to facilitate skill acquisition during discrete-trial instruction. We used an adapted alternating treatments design to compare the effects of 4 commonly used error-correction procedures on skill acquisition for 2 children with attention deficit hyperactivity disorder…

Order of Stimulus Presentation Influences Children's Acquisition in Receptive Identification Tasks

ERIC Educational Resources Information Center

Petursdottir, Anna Ingeborg; Aguilar, Gabriella

2016-01-01

Receptive identification is usually taught in matching-to-sample format, which entails the presentation of an auditory sample stimulus and several visual comparison stimuli in each trial. Conflicting recommendations exist regarding the order of stimulus presentation in matching-to-sample trials. The purpose of this study was to compare acquisition…

Site Matters: Multisite Randomized Trial of Motivational Enhancement Therapy in Community Drug Abuse Clinics

ERIC Educational Resources Information Center

Ball, Samuel A.; Martino, Steve; Nich, Charla; Frankforter, Tami L.; Van Horn, Deborah; Crits-Christoph, Paul; Woody, George E.; Obert, Jeanne L.; Farentinos, Christiane; Carroll, Kathleen M.

2007-01-01

The effectiveness of motivational enhancement therapy (MET) in comparison with counseling as usual (CAU) for increasing retention and reducing substance use was evaluated in a multisite randomized clinical trial. Participants were 461 outpatients treated by 31 therapists within 1 of 5 outpatient substance abuse programs. There were no retention…

An evaluation of malingering screens with competency to stand trial patients: a known-groups comparison.

PubMed

Vitacco, Michael J; Rogers, Richard; Gabel, Jason; Munizza, Janice

2007-06-01

The assessment of malingering is a fundamental component of forensic evaluations that should be considered with each referral. In systematizing the evaluation of malingering, one option is the standardized administration of screens as an initial step. The current study assessed the effectiveness of three common screening measures: the Miller Forensic Assessment of Symptoms Test (M-FAST; Miller, 2001), the Structured Inventory of Malingered Symptomatology (SIMS; Widows & Smith, 2004), and the Evaluation of Competency to Stand Trial-Revised Atypical Presentation Scale (ECST-R ATP; Rogers, Tillbrook, & Sewell, 2004). Using the Structured Interview of Reported Symptoms (SIRS) as the external criterion, 100 patients involved in competency to stand trial evaluations were categorized as either probable malingerers (n=21) or nonmalingerers (n=79). Each malingering scale produced robust effect sizes in this known-groups comparison. Results are discussed in relation to the comprehensive assessment of malingering within a forensic context.

Benchmarks for detecting 'breakthroughs' in clinical trials: empirical assessment of the probability of large treatment effects using kernel density estimation.

PubMed

Miladinovic, Branko; Kumar, Ambuj; Mhaskar, Rahul; Djulbegovic, Benjamin

2014-10-21

To understand how often 'breakthroughs,' that is, treatments that significantly improve health outcomes, can be developed. We applied weighted adaptive kernel density estimation to construct the probability density function for observed treatment effects from five publicly funded cohorts and one privately funded group. 820 trials involving 1064 comparisons and enrolling 331,004 patients were conducted by five publicly funded cooperative groups. 40 cancer trials involving 50 comparisons and enrolling a total of 19,889 patients were conducted by GlaxoSmithKline. We calculated that the probability of detecting treatment with large effects is 10% (5-25%), and that the probability of detecting treatment with very large treatment effects is 2% (0.3-10%). Researchers themselves judged that they discovered a new, breakthrough intervention in 16% of trials. We propose these figures as the benchmarks against which future development of 'breakthrough' treatments should be measured. 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.

Immune Checkpoint Inhibition in Hepatocellular Carcinoma: Basics and Ongoing Clinical Trials.

PubMed

Kudo, Masatoshi

2017-01-01

Clinical trials of antibodies targeting the immune checkpoint inhibitors programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for the treatment of advanced hepatocellular carcinoma (HCC) are ongoing. Expansion cohorts of a phase I/II trial of the anti-PD-1 antibody nivolumab in advanced HCC showed favorable results. Two phase III studies are currently ongoing: a comparison of nivolumab and sorafenib in the first-line setting for advanced HCC, and a comparison of the anti-PD-1 antibody pembrolizumab and a placebo in the second-line setting for patients with advanced HCC who progressed on sorafenib therapy. The combination of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies is being evaluated in other phase I/II trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. Immune checkpoint inhibitors may therefore open new doors to the treatment of HCC. © 2017 S. Karger AG, Basel.

Benefits of State-by-State Comparisons.

ERIC Educational Resources Information Center

Phillips, Gary W.

1991-01-01

Suggests that the National Assessment of Educational Progress's (NAEP) Trial State Assessment (TSA) will provide reliable and valid state-by-state comparisons of what students have learned and will assess their progress over time. The TSA will also provide information on home learning environments, instructional practices, educational resources,…

Modifying the clinical research infrastructure at a dedicated clinical trials unit: assessment of trial development, activation, and participant accrual

PubMed Central

Tang, Chad; Hess, Kenneth R.; Sanders, Dwana; Davis, Suzanne; Buzdar, Aman; Kurzrock, Razelle; Lee, J. Jack; Meric-Bernstam, Funda; Hong, David

2017-01-01

Purpose Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center and analyzed their effects on the trial activation timeline and enrollment. Experimental Design Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results We identified 3 facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship (industry [133 ICT and 133 non-ICT trials] or institutional [68 ICT and 68 non-ICT trials]). ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrollment (median difference of 0.3 months for industry vs. 1.2 months for institutional) (all matched P<0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional) (all matched P<0.05). Conclusions Use of a clinical research–focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. PMID:27852698

Modifying the Clinical Research Infrastructure at a Dedicated Clinical Trials Unit: Assessment of Trial Development, Activation, and Participant Accrual.

PubMed

Tang, Chad; Hess, Kenneth R; Sanders, Dwana; Davis, Suzanne E; Buzdar, Aman U; Kurzrock, Razelle; Lee, J Jack; Meric-Bernstam, Funda; Hong, David S

2017-03-15

Purpose: Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center (Houston, TX) and analyzed their effects on the trial activation timeline and enrolment. Experimental Design: Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database, we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results: We identified three facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship [industry (133 ICT and 133 non-ICT trials) or institutional (68 ICT and 68 non-ICT trials)]. ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrolment (median difference of 0.3 months for industry vs. 1.2 months for institutional; all matched P < 0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional; all matched P < 0.05). Conclusions: Use of a clinical research-focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. Clin Cancer Res; 23(6); 1407-13. ©2016 AACR . ©2016 American Association for Cancer Research.

PSYCHOTHERAPY VERSUS PHARMACOTHERAPY FOR POSTTRAUMATIC STRESS DISORDER: SYSTEMIC REVIEW AND META-ANALYSES TO DETERMINE FIRST-LINE TREATMENTS.

PubMed

Lee, Daniel J; Schnitzlein, Carla W; Wolf, Jonathan P; Vythilingam, Meena; Rasmusson, Ann M; Hoge, Charles W

2016-09-01

Current clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first-line treatment. Direct head-to-head comparisons are lacking. Systemic review of Medline, EMBASE, PILOTS, Cochrane Central Register of Controlled Trials, PsycINFO, and Global Health Library was conducted without language restrictions. Randomized clinical trials ≥8 weeks in duration using structured clinical interview-based outcome measures, active-control conditions (e.g. supportive psychotherapy), and intent-to-treat analysis were selected for analyses. Independent review, data abstraction, and bias assessment were performed using standardized processes. Study outcomes were grouped around conventional follow-up time periods (3, 6, and 9 months). Combined effect sizes were computed using meta-analyses for medication versus control, medication pre-/posttreatment, psychotherapy versus control, and psychotherapy pre-/posttreatment. Effect sizes for trauma-focused psychotherapies (TFPs) versus active control conditions were greater than medications versus placebo and other psychotherapies versus active controls. TFPs resulted in greater sustained benefit over time than medications. Sertraline, venlafaxine, and nefazodone outperformed other medications, although potential for methodological biases were high. Improvement following paroxetine and fluoxetine treatment was small. Venlafaxine and stress inoculation training (SIT) demonstrated large initial effects that decreased over time. Bupropion, citalopram, divalproex, mirtazapine, tiagabine, and topiramate failed to differentiate from placebo. Aripiprazole, divalproex, guanfacine, and olanzapine failed to differentiate from placebo when combined with an antidepressant. Study findings support use of TFPs over nontrauma-focused psychotherapy or medication as first-line interventions. Second-line interventions include SIT, and potentially sertraline or venlafaxine, rather than entire classes of medication, such as SSRIs. Future revisions of CPGs should prioritize studies that utilize active controls over waitlist or treatment-as-usual conditions. Direct head-to-head trials of TFPs versus sertraline or venlafaxine are needed. © 2016 Wiley Periodicals, Inc.

A randomised controlled trial of increasing fruit and vegetable intake and how this influences the carotenoid concentration and activities of PON-1 and LCAT in HDL from subjects with type 2 diabetes

PubMed Central

2014-01-01

Background High density lipoproteins (HDL) have many cardioprotective roles; however, in subjects with type 2 diabetes (T2D) these cardioprotective properties are diminished. Conversely, increased fruit and vegetable (F&V) intake may reduce cardiovascular disease risk, although direct trial evidence of a mechanism by which this occurs in subjects with T2D is lacking. Therefore, the aim of this study was to examine if increased F&V consumption influenced the carotenoid content and enzymes associated with the antioxidant properties of HDL in subjects with T2D. Methods Eighty obese subjects with T2D were randomised to a 1- or ≥6-portion/day F&V diet for 8-weeks. Fasting serum was collected pre- and post-intervention. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Carotenoids were measured in serum, HDL2 and HDL3 by high performance liquid chromatography. The activity of paraoxonase-1 (PON-1) was measured in serum, HDL2 and HDL3 by a spectrophotometric assay, while the activity of lecithin cholesterol acyltransferase (LCAT) was measured in serum, HDL2 and HDL3 by a fluorometric assay. Results In the ≥6- vs. 1-portion post-intervention comparisons, carotenoids increased in serum, HDL2 and particularly HDL3, (α-carotene, p = 0.008; β-cryptoxanthin, p = 0.042; lutein, p = 0.012; lycopene, p = 0.016), as did the activities of PON-1 and LCAT in HDL3 (p = 0.006 and 0.044, respectively). Conclusion To our knowledge, this is the first study in subjects with T2D to demonstrate that increased F&V intake augmented the carotenoid content and influenced enzymes associated with the antioxidant properties of HDL. We suggest that these changes would enhance the cardioprotective properties of this lipoprotein. Clinical trial registration ISRCTN21676269 PMID:24423117

Evaluation of the immediate effect of acupuncture on pain, cervical range of motion and electromyographic activity of the upper trapezius muscle in patients with nonspecific neck pain: study protocol for a randomized controlled trial.

PubMed

Calamita, Simone Aparecida Penimpedo; Biasotto-Gonzalez, Daniela Aparecida; De Melo, Nivea Cristina; dos Santos, Douglas Meira; de Lassa, Roberta; de Mendonça, Fabiana Sarilho; Oliveira, Claudia Santos; Amorim, César Ferreira; Gonzalez, Tabajara Oliveira; Fumagalli, Marco Antônio; de Gomes, Cid André Fidelis Paula; Politti, Fabiano

2015-03-19

Nonspecific neck pain can cause considerable suffering, possible disability and reductions in quality of life and productivity. The aim of the proposed study is to evaluate the immediate effect of acupuncture on pain, cervical range of motion and electromyographic activity of the upper trapezius muscle in patients with nonspecific neck pain. A total of 12 patients with nonspecific neck pain and 12 healthy subjects will be enrolled in a randomized, single-blind crossover study. Each subject will receive two forms of treatment in random order: a single session of traditional acupuncture (acupoints: triple energizer 5, 'Wai-guan' and large intestine 11, 'Qu-chi') and sham acupuncture. To eliminate carry-over treatment effects, a one-week wash-out period will be respected between sessions. Surface electromyography will be used to determine motor control in the upper trapezius muscle before and after treatment. The outcome measures in the group with neck pain will be a numerical pain rating scale (range: 0 (no pain) to 10 (maximum pain)), documentation of the pain area on a body chart and cervical range of motion. Comparisons before and after acupuncture treatment will demonstrate whether acupoints affect the activity of the upper trapezius muscle, pain and cervical range of motion. The purpose of this randomized clinical trial is to evaluate the immediate effect of acupuncture on pain, cervical range of motion and electromyographic activity of the upper trapezius muscle in patients with nonspecific neck pain. Data will be published after the study is completed. The study will support the practice of evidence-based physical therapy for individuals with nonspecific neck pain. This trial was registered with Clinicaltrials.gov (identifier: NCT0984021 ) on 7 November 2013 ( https://clinicaltrials.gov/ct2/show/NCT01984021 ).

Comparison of ESSDAI and ClinESSDAI in potential optimisation of trial outcomes in primary Sjögren's syndrome: examination of data from the UK Primary Sjögren's Syndrome Registry.

PubMed

Dumusc, Alexandre; Ng, Wan-Fai; James, Katherine; Griffiths, Bridget; Price, Elizabeth; Pease, Colin; Emery, Paul; Lanyon, Peter; Jones, Adrian; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Gupta, Monica; McLaren, John; Cooper, Annie; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Barone, Francesca; Fisher, Benjamin; Rauz, Saaeha; Richards, Andrea; Bowman, Simon

2018-02-14

To assess the use of the Clinical EULAR Sjögren's Syndrome Disease Activity Index (ClinESSDAI), a version of the ESSDAI without the biological domain, for assessing potential eligibility and outcomes for clinical trials in patients with primary Sjögren's syndrome (pSS), according to the new ACR-EULAR classification criteria, from the UK Primary Sjögren's Syndrome Registry (UKPSSR). A total of 665 patients from the UKPSSR cohort were analysed at their time of inclusion in the registry. ESSDAI and ClinESSDAI were calculated for each patient. For different disease activity index cut-off values, more potentially eligible participants were found when ClinESSDAI was used than with ESSDAI. The distribution of patients according to defined disease activity levels did not differ statistically (chi2 p = 0.57) between ESSDAI and ClinESSDAI for moderate disease activity (score ≥5 and <14; ESSDAI 36.4%; ClinESSDA 36.5%) or high disease activity (score ≥14; ESSDAI 5.4%; ClinESSDAI 6.8%). We did not find significant differences between the indexes in terms of activity levels for individual domains, with the exception of the articular domain. We found a good level of agreement between both indexes, and a positive correlation between lymphadenopathy and glandular domains with the use of either index and with different cut-off values. With the use of ClinESSDAI, the minimal clinically important improvement value was more often achievable with a one grade improvement of a single domain than with ESSDAI. We observed similar results when using the new ACR-EULAR classification criteria or the previously used American-European Consensus Group (AECG) classification criteria for pSS. In the UKPSSR population, the use of ClinESSDAI instead of ESSDAI did not lead to significant changes in score distribution, potential eligibility or outcome measurement in trials, or in routine care when immunological tests are not available. These results need to be confirmed in other cohorts and with longitudinal data.

African American Veterans Storytelling: A Multisite Randomized Trial to Improve Hypertension.

PubMed

Houston, Thomas K; Fix, Gemmae M; Shimada, Stephanie L; Long, Judith A; Gordon, Howard S; Pope, Charlene; Volkman, Julie; Allison, Jeroan J; DeLaughter, Kathryn; Orner, Michelle; Bokhour, Barbara G

2017-09-01

Disparities in hypertension control persist for African American Veterans. To enhance cultural relevance of hypertension control self-management education, in a multisite, stratified randomized trial, we tested an interactive Veteran-to-Veteran storytelling digital video disk (DVD) intervention created with Veteran partners, versus an education-only DVD comparison. At 3 VA facilities, African American Veterans with uncontrolled hypertension were randomized to storytelling DVD intervention or didactic comparison DVD and followed for 6 months. We hypothesized that follow-up blood pressure (BP) would be lower among Veterans in the intervention group. African American Veterans (N=619) were 92% male, 39% over age 65, most had a high-school education, over 50% of both the intervention and comparison group reported a household income of <$20,000, and 40% had less than adequate health literacy. At baseline, mean intervention and comparison group BPs were 138/80 and 139/81 mm Hg, respectively; at 6 months, mean systolic BP (SBP) increased by 0.1 in the intervention group and by 1.9 for the comparison group; diastolic BP fell by 0.1 in the intervention group and rose by 0.2 in the comparison group. No differences between the intervention and control groups were statistically significant (all P>0.3). Site differences were large; at one, the intervention group improved while the comparison groups deteriorated, resulting in 6.3 and 3.9 mm Hg more improvement for the intervention group in SBP and diastolic BP (P=0.06 and 0.04), respectively; at the other 2 sites, there were positive and negative changes, all small, in the 2 measures, with minimal differences-one site favored the comparison group and the other, the intervention (these comparisons did not approach statistical significance (all P>0.20). In a secondary analysis stratified by baseline BP, there was no intervention effect among those with uncontrolled BP, but intervention patients who were in control at baseline were more likely to stay in control, compared with comparison [SBP increase by 6.3 mm Hg (SD=14.4) among intervention, and by 10.9 mm Hg (SD=16.9) in comparison, P=0.02]. In this multisite trial, we did not find a significant overall storytelling intervention effect (Clinicaltrials.gov Reg. #NCT01276197).

Sensation seeking amongst healthy volunteers participating in phase I clinical trials.

PubMed Central

Farré, M; Lamas, X; Camí, J

1995-01-01

1. Phase I clinical trials are usually carried out in healthy volunteers. In addition to economic gain, factors that may influence willingness to participate include scientific interest, curiosity and choice for risky activities. 2. We assessed the relationship between personality variables and volunteering for clinical pharmacology research. Two personality questionnaires, the Sensation Seeking Scale (SSS, form V) and the Eysenck Personality Questionnaire (EPQ), were administered to 48 male healthy university students who volunteered to participate in a phase I clinical trial and to 43 male university students who were not willing to participate in phase I clinical trials. General norm data were also used for the comparison of results. 3. When healthy volunteers were compared with unwilling subjects, significant differences were found in thrill-and-adventure seeking (7.9 vs 6.7, P = 0.0034), experience seeking (6.4 vs 5.2, P = 0.0012), disinhibition (6.2 vs 4.3, P < 0.0001), boredom susceptibility (3.9 vs 2.8, P = 0.0073), total sensation seeking trait (24.3 vs 19.0, P < 0.0001), extraversion (15.1 vs 13.3, P = 0.0490), and psychoticism (4.4 vs 3.5, P = 0.0086). When healthy volunteers were compared with general norm data similar statistically significant differences were found in all these scales, except for boredom susceptibility and psychoticism. 4. The personality profile of healthy volunteers was characterized by a higher sensation seeking trait and extraversion as compared with individuals who were not willing to participate in phase I clinical trials and general norm data. PMID:7640147

The Novel Antipsychotic Cariprazine (RGH-188): State-of-the-Art in the Treatment of Psychiatric Disorders.

PubMed

De Berardis, Domenico; Orsolini, Laura; Iasevoli, Felice; Prinzivalli, Emiliano; de Bartolomeis, Andrea; Serroni, Nicola; Mazza, Monica; Valchera, Alessandro; Fornaro, Michele; Vecchiotti, Roberta; Carano, Alessandro; Sepede, Gianna; Vellante, Federica; Matarazzo, Ilaria; Pompili, Maurizio; Perna, Giampaolo; Conti, Chiara; Segura-García, Cristina; Martinotti, Giovanni; Di Giannantonio, Massimo

2016-01-01

Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in late-stage clinical development (phase III clinical trials) in patients with schizophrenia (S) and in patients with bipolar disorder (BD), as well as an adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD. Cariprazine has completed phase III trials for the acute treatment of schizophrenia and bipolar mania, phase II trials for the bipolar depression and MDD whilst it is undergoing phase III trials as an adjunct to antidepressants. The present review aims at proving a comprehensive summary of the current evidence on the safety, tolerability and efficacy of cariprazine in the treatment of schizophrenia, BD (manic/mixed/ depressive episode) and MDD. A systematic search was conducted on PubMed/Medline/ Scopus and the database on Clinical Trials from inception until April 2015 by typing a set of specified keywords. Available evidence seems to support cariprazine efficacy in the treatment of cognitive and negative symptoms of schizophrenia. Preliminary findings suggest its antimanic activity whilst it is still under investigation its efficacy in the treatment of bipolar depression and MDD. Furthermore, the available data seems not to allow judgements about its antipsychotic potential in comparison with currently prescribed antipsychotics. Further studies should be carried out to better investigate its pharmacodynamic and clinical potential, particularly as alternative to current antipsychotic drugs.

The utility of levosimendan in the treatment of heart failure.

PubMed

Lehtonen, Lasse; Põder, Pentti

2007-01-01

Calcium sensitizers are a new group of inotropic drugs. Levosimendan is the only calcium sensitizer in clinical use in Europe. Its mechanism of action includes both calcium sensitization of contractile proteins and the opening of adenosine triphosphate (ATP)-dependent potassium channels as mechanism of vasodilation. The combination of K-channel opening with positive inotropy offers potential benefits in comparison to currently available intravenous inotropes, since K-channel opening protects myocardium during ischemia. Due to the calcium-dependent binding of levosimendan to troponin C, the drug increases contractility without negative lusitropic effects. In patients with heart failure levosimendan dose-dependently increases cardiac output and reduces pulmonary capillary wedge pressure. Since levosimendan has an active metabolite OR-1896 with a half-life of some 80 hours, the duration of the hemodynamic effects significantly exceeds the 1-hour half-life of the parent compound. The hemodynamic effects of the levosimendan support its use in acute and postoperative heart failure. Several moderate-size trials (LIDO, RUSSLAN, CASINO) have previously suggested that the drug might even improve the prognosis of patients with decompensated heart failure. These trials were carried out in patients with high filling pressures. Recently two larger trials (SURVIVE and REVIVE) in patients who were hospitalized because of worsening heart failure have been finalized. These trials did not require filling pressures to be measured. The two trials showed that levosimendan improves the symptoms of heart failure, but does not improve survival. The results raise the question whether a 24-hour levosimendan infusion can be used without invasive hemodynamic monitoring.

Systematic review of efficacy of cognitive behaviour therapies in childhood and adolescent depressive disorder

PubMed Central

Harrington, Richard; Whittaker, Jane; Shoebridge, Philip; Campbell, Fiona

1998-01-01

Objective: To determine whether cognitive behaviour therapy is an effective treatment for childhood and adolescent depressive disorder. Design: Systematic review of six randomised trials comparing the efficacy of cognitive behaviour therapy with inactive interventions in subjects aged 8 to 19 years with depressive disorder. Main outcome measure: Remission from depressive disorder. Results: The rate of remission from depressive disorder was higher in the therapy group (129/208; 62%) than in the comparison group (61/168; 36%). The pooled odds ratio was 3.2 (95% confidence interval 1.9 to 5.2), suggesting a significant benefit of active treatment. Most studies, however, were based on relatively mild cases of depression and were of only moderate quality. Conclusions: Cognitive behaviour therapy may be of benefit for depressive disorder of moderate severity in children and adolescents. It cannot, however, yet be recommended for severe depression. Definitive large trials will be required to determine whether the results of this systematic review are reliable. Key messages Depressive disorders are a common problem in child psychiatric clinics, but a recent systematic review found that tricyclic medication was of unproved benefit This systematic review identified six randomised trials of a psychological treatment—cognitive behaviour therapy—in subjects aged 8 to 19 years with depressive disorder The results seemed to show that cognitive behaviour therapy is an effective treatment for depressive disorder of moderate severity Because of the small number of trials available for this quantitative analysis definitive large trials will be required to determine whether the present results are reliable PMID:9596592

Effectiveness and cost-effectiveness of rehabilitation after lumbar disc surgery (REALISE): design of a randomised controlled trial

PubMed Central

2013-01-01

Background Patients who undergo lumbar disc surgery for herniated discs, are advocated two different postoperative management strategies: a watchful waiting policy, or referral for rehabilitation immediately after discharge from the hospital. A direct comparison of the effectiveness and cost-effectiveness of these two strategies is lacking. Methods/Design A randomised controlled trial will be conducted with an economic evaluation alongside to assess the (cost-) effectiveness of rehabilitation after lumbar disc surgery. Two hundred patients aged 18–70 years with a clear indication for lumbar disc surgery of a single level herniated disc will be recruited and randomly assigned to either a watchful waiting policy for first six weeks or exercise therapy starting immediately after discharge from the hospital. Exercise therapy will focus on resumption of activities of daily living and return to work. Therapists will tailor the intervention to the individual patient’s needs. All patients will be followed up by the neurosurgeon six weeks postoperatively. Main outcome measures are: functional status, pain intensity and global perceived recovery. Questionnaires will be completed preoperatively and at 3, 6, 9, 12 and 26 weeks after surgery. Data will be analysed according to the intention-to-treat principle, using a linear mixed model for continuous outcomes and a generalised mixed model for dichotomous outcomes. The economic evaluation will be performed from a societal perspective. Discussion The results of this trial may lead to a more consistent postoperative strategy for patients who will undergo lumbar disc surgery. Trial registration Netherlands Trial Register: NTR3156 PMID:23560810

Experience Corps: A dual trial to promote the health of older adults and children's academic success

PubMed Central

Fried, Linda P.; Carlson, Michelle C.; McGill, Sylvia; Seeman, Teresa; Xue, Qian-Li; Frick, Kevin; Tan, Erwin; Tanner, Elizabeth K.; Barron, Jeremy; Frangakis, Constantine; Piferi, Rachel; Martinez, Iveris; Gruenewald, Tara; Martin, Barbara K.; Berry-Vaughn, Laprisha; Stewart, John; Dickersin, Kay; Willging, Paul R.; Rebok, George W.

2014-01-01

Background As the population ages, older adults are seeking meaningful, and impactful, post-retirement roles. As a society, improving the health of people throughout longer lives is a major public health goal. This paper presents the design and rationale for an effectiveness trial of Experience Corps™, an intervention created to address both these needs. This trial evaluates (1) whether senior volunteer roles within Experience Corps™ beneficially impact children's academic achievement and classroom behavior in public elementary schools and (2) impact on the health of volunteers. Methods Dual evaluations of (1) an intention-to-treat trial randomizing eligible adults 60 and older to volunteer service in Experience Corps™, or to a control arm of usual volunteering opportunities, and (2) a comparison of eligible public elementary schools receiving Experience Corps™ to matched, eligible control schools in a 1:1 control:intervention school ratio. Outcomes For older adults, the primary outcome is decreased disability in mobility and Instrumental Activities of Daily Living (IADL). Secondary outcomes are decreased frailty, falls, and memory loss; slowed loss of strength, balance, walking speed, cortical plasticity, and executive function; objective performance of IADLs; and increased social and psychological engagement. For children, primary outcomes are improved reading achievement and classroom behavior in Kindergarten through the 3rd grade; secondary outcomes are improvements in school climate, teacher morale and retention, and teacher perceptions of older adults. Summary This trial incorporates principles and practices of community-based participatory research and evaluates the dual benefit of a single intervention, versus usual opportunities, for two generations: older adults and children. PMID:23680986

Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations.

PubMed

Taylor, Ann M; Phillips, Kristine; Patel, Kushang V; Turk, Dennis C; Dworkin, Robert H; Beaton, Dorcas; Clauw, Daniel J; Gignac, Monique A M; Markman, John D; Williams, David A; Bujanover, Shay; Burke, Laurie B; Carr, Daniel B; Choy, Ernest H; Conaghan, Philip G; Cowan, Penney; Farrar, John T; Freeman, Roy; Gewandter, Jennifer; Gilron, Ian; Goli, Veeraindar; Gover, Tony D; Haddox, J David; Kerns, Robert D; Kopecky, Ernest A; Lee, David A; Malamut, Richard; Mease, Philip; Rappaport, Bob A; Simon, Lee S; Singh, Jasvinder A; Smith, Shannon M; Strand, Vibeke; Tugwell, Peter; Vanhove, Gertrude F; Veasley, Christin; Walco, Gary A; Wasan, Ajay D; Witter, James

2016-09-01

Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.

Sample size re-estimation and other midcourse adjustments with sequential parallel comparison design.

PubMed

Silverman, Rachel K; Ivanova, Anastasia

2017-01-01

Sequential parallel comparison design (SPCD) was proposed to reduce placebo response in a randomized trial with placebo comparator. Subjects are randomized between placebo and drug in stage 1 of the trial, and then, placebo non-responders are re-randomized in stage 2. Efficacy analysis includes all data from stage 1 and all placebo non-responding subjects from stage 2. This article investigates the possibility to re-estimate the sample size and adjust the design parameters, allocation proportion to placebo in stage 1 of SPCD, and weight of stage 1 data in the overall efficacy test statistic during an interim analysis.

Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study.

PubMed

Abraha, Iosief; Cherubini, Antonio; Cozzolino, Francesco; De Florio, Rita; Luchetta, Maria Laura; Rimland, Joseph M; Folletti, Ilenia; Marchesi, Mauro; Germani, Antonella; Orso, Massimiliano; Eusebi, Paolo; Montedori, Alessandro

2015-05-27

To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. Meta-epidemiological study. Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included. From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value <1 indicated larger treatment effects in mITT trials than in other trial categories). 50 meta-analyses and 322 comparisons of randomised trials (from 84 ITT trials, 118 mITT trials, and 108 no ITT trials; 12 trials contributed twice to the analysis) were examined. Compared with ITT trials, mITT trials showed a larger intervention effect (pooled ratio of odds ratios 0.83 (95% confidence interval 0.71 to 0.96), P=0.01; between meta-analyses variance τ(2)=0.13). Adjustments for sample size, type of centre, funding, items of risk of bias, post-randomisation exclusions, and variance of log odds ratio yielded consistent results (0.80 (0.69 to 0.94), P=0.005; τ(2)=0.08). After exclusion of five influential studies, results remained consistent (0.85 (0.75 to 0.98); τ(2)=0.08). The comparison between mITT trials and no ITT trials showed no statistical difference between the two groups (adjusted ratio of odds ratios 0.92 (0.70 to 1.23); τ(2)=0.57). Trials that deviated from the intention to treat analysis showed larger intervention effects than trials that reported the standard approach. Where an intention to treat analysis is impossible to perform, authors should clearly report who is included in the analysis and attempt to perform multiple imputations. © Abraha et al 2015.

To Trust or Not to Trust: Social Decision Making in Post-institutionalized, Internationally Adopted Youth

PubMed Central

Pitula, Clio E.; Wenner, Jennifer A.; Gunnar, Megan R.; Thomas, Kathleen M.

2015-01-01

Chronic parental maltreatment has been associated with lower levels of interpersonal trust, and depriving environments have been shown to predict shortsighted, risk-averse decision-making. The present study examined whether a circumscribed period of adverse care occurring only early in life was associated with biases in trust behavior. Fifty-three post-institutionalized (PI) youth, adopted internationally on average by one year of age, and 33 never-institutionalized, non-adopted youth (M age = 12.9 years) played a trust game. Participants decided whether or not to share coins with a different anonymous peer in each trial with the potential to receive a larger number of coins in return. Trials were presented in blocks that varied in the degree to which the peers behaved in a trustworthy (reciprocal) or untrustworthy (non-reciprocal) manner. A comparison condition consisted of a computerized lottery with the same choices and probabilistic risk as the peer trials. Non-adopted comparison youth showed a tendency to share more with peers than to invest in the lottery and tended to maintain their level of sharing across trials despite experiencing trials in which peers failed to reciprocate. In contrast, PI children, particularly those who were adopted over a year of age, shared less with peers than they invested in the lottery and quickly adapted their sharing behavior to peers' responses. These results suggest that PI youth were more mistrusting, more sensitive to both defection and reciprocation, and potentially more accurate in their trusting decisions than comparison youth. Results support the presence of a sensitive period for the development of trust in others, whereby conditions early in life may set long-term biases in decision-making. PMID:27089448

To trust or not to trust: social decision-making in post-institutionalized, internationally adopted youth.

PubMed

Pitula, Clio E; Wenner, Jennifer A; Gunnar, Megan R; Thomas, Kathleen M

2017-05-01

Chronic parental maltreatment has been associated with lower levels of interpersonal trust, and depriving environments have been shown to predict short-sighted, risk-averse decision-making. The present study examined whether a circumscribed period of adverse care occurring only early in life was associated with biases in trust behavior. Fifty-three post-institutionalized (PI) youth, adopted internationally on average by 1 year of age, and 33 never-institutionalized, non-adopted youth (M age  = 12.9 years) played a trust game. Participants decided whether or not to share coins with a different anonymous peer in each trial with the potential to receive a larger number of coins in return. Trials were presented in blocks that varied in the degree to which the peers behaved in a trustworthy (reciprocal) or untrustworthy (non-reciprocal) manner. A comparison condition consisted of a computerized lottery with the same choices and probabilistic risk as the peer trials. Non-adopted comparison youth showed a tendency to share more with peers than to invest in the lottery and tended to maintain their level of sharing across trials despite experiencing trials in which peers failed to reciprocate. In contrast, PI children, particularly those who were adopted over 1 year of age, shared less with peers than they invested in the lottery and quickly adapted their sharing behavior to peers' responses. These results suggest that PI youth were more mistrusting, more sensitive to both defection and reciprocation, and potentially more accurate in their trusting decisions than comparison youth. Results support the presence of a sensitive period for the development of trust in others, whereby conditions early in life may set long-term biases in decision-making. © 2016 John Wiley & Sons Ltd.