Muscle activation timing and balance response in chronic lower back pain patients with associated radiculopathy.

PubMed

Frost, Lydia R; Brown, Stephen H M

2016-02-01

Patients with chronic low back pain and associated radiculopathy present with neuromuscular symptoms both in their lower back and down their leg; however, investigations of muscle activation have so far been isolated to the lower back. During balance perturbations, it is necessary that lower limb muscles activate with proper timing and sequencing along with the lower back musculature to efficiently regain balance control. Patients with chronic low back pain and radiculopathy and matched controls completed a series of balance perturbations (rapid bilateral arm raise, unanticipated and anticipated sudden loading, and rapid rise to toe). Muscle activation timing and sequencing as well as kinetic response to the perturbations were analyzed. Patients had significantly delayed lower limb muscle activation in rapid arm raise trials as compared to controls. In sudden loading trials, muscle activation timing was not delayed in patients; however, some differences in posterior chain muscle activation sequencing were present. Patients demonstrated less anterior-posterior movement in unanticipated sudden loading trials, and greater medial-lateral movement in rise to toe trials. Patients with low back pain and radiculopathy demonstrated some significant differences from control participants in terms of muscle activation timing, sequencing, and overall balance control. The presence of differences between patients and controls, specifically in the lower limb, indicates that radiculopathy may play a role in altering balance control in these patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

The potential benefit of the placebo effect in sham-controlled trials: implications for risk-benefit assessments and informed consent

PubMed Central

Brim, Remy L; Miller, Franklin G

2013-01-01

There has been considerable debate surrounding the ethics of sham-controlled trials of procedures and interventions. Critics argue that these trials are unethical because participants assigned to the control group have no prospect of benefit from the trial, yet they are exposed to all the risks of the sham intervention. However, the placebo effect associated with sham procedures can often be substantial and has been well documented in the scientific literature. We argue that, in light of the scientific evidence supporting the benefits of sham interventions for pain and Parkinson's disease that stem from the placebo effect, these sham-controlled trials should be considered as offering potential direct benefit to participants. If scientific evidence demonstrates the positive effect of placebo from sham interventions on other conditions, sham-controlled trials of interventions for the treatment of these conditions should be considered to have prospects of benefit as well. This potential benefit should be taken into account by research ethics committees in risk-benefit analyses, and be included in informed consent documents. PMID:23239742

Differentiating closed-loop cortical intention from rest: building an asynchronous electrocorticographic BCI.

PubMed

Williams, Jordan J; Rouse, Adam G; Thongpang, Sanitta; Williams, Justin C; Moran, Daniel W

2013-08-01

Recent experiments have shown that electrocorticography (ECoG) can provide robust control signals for a brain-computer interface (BCI). Strategies that attempt to adapt a BCI control algorithm by learning from past trials often assume that the subject is attending to each training trial. Likewise, automatic disabling of movement control would be desirable during resting periods when random brain fluctuations might cause unintended movements of a device. To this end, our goal was to identify ECoG differences that arise between periods of active BCI use and rest. We examined spectral differences in multi-channel, epidural micro-ECoG signals recorded from non-human primates when rest periods were interleaved between blocks of an active BCI control task. Post-hoc analyses demonstrated that these states can be decoded accurately on both a trial-by-trial and real-time basis, and this discriminability remains robust over a period of weeks. In addition, high gamma frequencies showed greater modulation with desired movement direction, while lower frequency components demonstrated greater amplitude differences between task and rest periods, suggesting possible specialized BCI roles for these frequencies. The results presented here provide valuable insight into the neurophysiology of BCI control as well as important considerations toward the design of an asynchronous BCI system.

Differentiating closed-loop cortical intention from rest: building an asynchronous electrocorticographic BCI

NASA Astrophysics Data System (ADS)

Williams, Jordan J.; Rouse, Adam G.; Thongpang, Sanitta; Williams, Justin C.; Moran, Daniel W.

2013-08-01

Objective. Recent experiments have shown that electrocorticography (ECoG) can provide robust control signals for a brain-computer interface (BCI). Strategies that attempt to adapt a BCI control algorithm by learning from past trials often assume that the subject is attending to each training trial. Likewise, automatic disabling of movement control would be desirable during resting periods when random brain fluctuations might cause unintended movements of a device. To this end, our goal was to identify ECoG differences that arise between periods of active BCI use and rest. Approach. We examined spectral differences in multi-channel, epidural micro-ECoG signals recorded from non-human primates when rest periods were interleaved between blocks of an active BCI control task. Main Results. Post-hoc analyses demonstrated that these states can be decoded accurately on both a trial-by-trial and real-time basis, and this discriminability remains robust over a period of weeks. In addition, high gamma frequencies showed greater modulation with desired movement direction, while lower frequency components demonstrated greater amplitude differences between task and rest periods, suggesting possible specialized BCI roles for these frequencies. Significance. The results presented here provide valuable insight into the neurophysiology of BCI control as well as important considerations toward the design of an asynchronous BCI system.

Intensive glycemic control and cardiovascular disease: an update.

PubMed

Brown, Aparna; Reynolds, L Raymond; Bruemmer, Dennis

2010-07-01

Cardiovascular complications constitute the major cause of morbidity and mortality in patients with diabetes. The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) provided consistent evidence that intensive glycemic control prevents the development and progression of microvascular complications in patients with type 1 or type 2 diabetes. However, whether intensive glucose lowering also prevents macrovascular disease and major cardiovascular events remains unclear. Extended follow-up of participants in these studies demonstrated that intensive glycemic control reduced the long-term incidence of myocardial infarction and death from cardiovascular disease. By contrast, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, and Veterans Affairs Diabetes Trial (VADT) results suggested that intensive glycemic control to near normoglycemia had either no, or potentially even a detrimental, effect on cardiovascular outcomes. This article discusses the effects of intensive glycemic control on cardiovascular disease, and examines key differences in the design of these trials that might have contributed to their disparate findings. Recommendations from the current joint ADA, AHA, and ACCF position statement on intensive glycemic control and prevention of cardiovascular disease are highlighted.

High School Students with Reading Comprehension Difficulties: Results of a Randomized Control Trial of a Two-Year Reading Intervention

ERIC Educational Resources Information Center

Vaughn, Sharon; Roberts, Greg; Wexler, Jade; Vaughn, Michael G.; Fall, Anna-Mária; Schnakenberg, Jennifer B.

2015-01-01

A 2-year, randomized control trial with 9th to 10th grade students with significant reading problems was provided for 50 minutes a day in small groups. Comparison students were provided an elective class and treatment students the reading intervention. Students were identified as demonstrating reading difficulties through failure on their state…

Cluster Randomized Test-Negative Design (CR-TND) Trials: A Novel and Efficient Method to Assess the Efficacy of Community Level Dengue Interventions.

PubMed

Anders, Katherine L; Cutcher, Zoe; Kleinschmidt, Immo; Donnelly, Christl A; Ferguson, Neil M; Indriani, Citra; O'Neill, Scott L; Jewell, Nicholas P; Simmons, Cameron P

2018-05-07

Cluster randomized trials are the gold standard for assessing efficacy of community-level interventions, such as vector control strategies against dengue. We describe a novel cluster randomized trial methodology with a test-negative design, which offers advantages over traditional approaches. It utilizes outcome-based sampling of patients presenting with a syndrome consistent with the disease of interest, who are subsequently classified as test-positive cases or test-negative controls on the basis of diagnostic testing. We use simulations of a cluster trial to demonstrate validity of efficacy estimates under the test-negative approach. This demonstrates that, provided study arms are balanced for both test-negative and test-positive illness at baseline and that other test-negative design assumptions are met, the efficacy estimates closely match true efficacy. We also briefly discuss analytical considerations for an odds ratio-based effect estimate arising from clustered data, and outline potential approaches to analysis. We conclude that application of the test-negative design to certain cluster randomized trials could increase their efficiency and ease of implementation.

Effect of an Automated Training Presentation on Pre-Service Behavior Analysts' Implementation of Trial-Based Functional Analysis

ERIC Educational Resources Information Center

Lambert, Joseph M.; Lloyd, Blair P.; Staubitz, Johanna L.; Weaver, Emily S.; Jennings, Chelsea M.

2014-01-01

The trial-based functional analysis (FA) is a useful alternative to the traditional FA in contexts in which it is challenging to establish environmental control for extended periods of time. Previous researchers have demonstrated that others can be trained to conduct trial-based FAs with high procedural fidelity by providing a didactic…

Effect of repeated sprints on postprandial endothelial function and triacylglycerol concentrations in adolescent boys.

PubMed

Sedgwick, Matthew J; Morris, John G; Nevill, Mary E; Barrett, Laura A

2015-01-01

This study investigated whether repeated, very short duration sprints influenced endothelial function (indicated by flow-mediated dilation) and triacylglycerol concentrations following the ingestion of high-fat meals in adolescent boys. Nine adolescent boys completed two, 2-day main trials (control and exercise), in a counter-balanced, cross-over design. Participants were inactive on day 1 of the control trial but completed 40 × 6 s maximal cycle sprints on day 1 of the exercise trial. On day 2, capillary blood samples were collected and flow-mediated dilation measured prior to, and following, ingestion of a high-fat breakfast and lunch. Fasting flow-mediated dilation and plasma triacylglycerol concentration were similar in the control and exercise trial (P > 0.05). In the control trial, flow-mediated dilation was reduced by 20% and 27% following the high-fat breakfast and lunch; following exercise these reductions were negated (main effect trial, P < 0.05; interaction effect trial × time, P < 0.05). The total area under the plasma triacylglycerol concentration versus time curve was 13% lower on day 2 in the exercise trial compared to the control trial (8.65 (0.97) vs. 9.92 (1.16) mmol · l(-1) · 6.5 h, P < 0.05). These results demonstrate that repeated 6 s maximal cycle sprints can have beneficial effects on postprandial endothelial function and triacylglycerol concentrations in adolescent boys.

Effects of Fructans from Mexican Agave in Newborns Fed with Infant Formula: A Randomized Controlled Trial

PubMed Central

López-Velázquez, Gabriel; Parra-Ortiz, Minerva; De la Mora-De la Mora, Ignacio; García-Torres, Itzhel; Enríquez-Flores, Sergio; Alcántara-Ortigoza, Miguel Angel; González-del Angel, Ariadna; Velázquez-Aragón, José; Ortiz-Hernández, Rosario; Cruz-Rubio, José Manuel; Villa-Barragán, Pablo; Jiménez-Gutiérrez, Carlos; Gutiérrez-Castrellón, Pedro

2015-01-01

Background: The importance of prebiotics consumption is increasing all over the world due to their beneficial effects on health. Production of better prebiotics from endemic plants raises possibilities to enhance nutritional effects in vulnerable population groups. Fructans derived from Agave Plant have demonstrated their safety and efficacy as prebiotics in animal models. Recently, the safety in humans of two fructans obtained from Agave tequilana (Metlin® and Metlos®) was demonstrated. Methods: This study aimed to demonstrate the efficacy as prebiotics of Metlin® and Metlos® in newborns of a randomized, double blind, controlled trial with a pilot study design. Biological samples were taken at 20 ± 7 days, and three months of age from healthy babies. Outcomes of efficacy include impact on immune response, serum ferritin, C-reactive protein, bone metabolism, and gut bacteria changes. Results: There were differences statistically significant for the groups of infants fed only with infant formula and with formula enriched with Metlin® and Metlos®. Conclusions: Our results support the efficacy of Metlin® and Metlos® as prebiotics in humans, and stand the bases to recommend their consumption. Trial Registration: ClinicalTrials.gov, NCT 01251783. PMID:26529006

Renal denervation for the management of resistant hypertension

PubMed Central

Patel, Hitesh C; Hayward, Carl; Vassiliou, Vassilis; Patel, Ketna; Howard, James P; Di Mario, Carlo

2015-01-01

Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established. PMID:26672761

A Randomized Controlled Trial of the First Step to Success Early Intervention: Demonstration of Program Efficacy Outcomes in a Diverse, Urban School District

ERIC Educational Resources Information Center

Walker, Hill M.; Seeley, John R.; Small, Jason; Severson, Herbert H.; Graham, Bethany A.; Feil, Edward G.; Serna, Loretta; Golly, Annemieke M.; Forness, Steven R.

2009-01-01

This article reports on a randomized controlled trial of the First Step to Success early intervention that was conducted over a 4-year period in Albuquerque Public Schools. First Step is a selected intervention for students in Grades 1 through 3 with externalizing behavior problems, and it addresses secondary prevention goals and objectives. It…

The curse of planning: dissecting multiple reinforcement-learning systems by taxing the central executive.

PubMed

Otto, A Ross; Gershman, Samuel J; Markman, Arthur B; Daw, Nathaniel D

2013-05-01

A number of accounts of human and animal behavior posit the operation of parallel and competing valuation systems in the control of choice behavior. In these accounts, a flexible but computationally expensive model-based reinforcement-learning system has been contrasted with a less flexible but more efficient model-free reinforcement-learning system. The factors governing which system controls behavior-and under what circumstances-are still unclear. Following the hypothesis that model-based reinforcement learning requires cognitive resources, we demonstrated that having human decision makers perform a demanding secondary task engenders increased reliance on a model-free reinforcement-learning strategy. Further, we showed that, across trials, people negotiate the trade-off between the two systems dynamically as a function of concurrent executive-function demands, and people's choice latencies reflect the computational expenses of the strategy they employ. These results demonstrate that competition between multiple learning systems can be controlled on a trial-by-trial basis by modulating the availability of cognitive resources.

The Curse of Planning: Dissecting multiple reinforcement learning systems by taxing the central executive

PubMed Central

Otto, A. Ross; Gershman, Samuel J.; Markman, Arthur B.; Daw, Nathaniel D.

2013-01-01

A number of accounts of human and animal behavior posit the operation of parallel and competing valuation systems in the control of choice behavior. Along these lines, a flexible but computationally expensive model-based reinforcement learning system has been contrasted with a less flexible but more efficient model-free reinforcement learning system. The factors governing which system controls behavior—and under what circumstances—are still unclear. Based on the hypothesis that model-based reinforcement learning requires cognitive resources, we demonstrate that having human decision-makers perform a demanding secondary task engenders increased reliance on a model-free reinforcement learning strategy. Further, we show that across trials, people negotiate this tradeoff dynamically as a function of concurrent executive function demands and their choice latencies reflect the computational expenses of the strategy employed. These results demonstrate that competition between multiple learning systems can be controlled on a trial-by-trial basis by modulating the availability of cognitive resources. PMID:23558545

An optimised patient information sheet did not significantly increase recruitment or retention in a falls prevention study: an embedded randomised recruitment trial.

PubMed

Cockayne, Sarah; Fairhurst, Caroline; Adamson, Joy; Hewitt, Catherine; Hull, Robin; Hicks, Kate; Keenan, Anne-Maree; Lamb, Sarah E; Green, Lorraine; McIntosh, Caroline; Menz, Hylton B; Redmond, Anthony C; Rodgers, Sara; Torgerson, David J; Vernon, Wesley; Watson, Judith; Knapp, Peter; Rick, Jo; Bower, Peter; Eldridge, Sandra; Madurasinghe, Vichithranie W; Graffy, Jonathan

2017-03-28

Randomised controlled trials are generally regarded as the 'gold standard' experimental design to determine the effectiveness of an intervention. Unfortunately, many trials either fail to recruit sufficient numbers of participants, or recruitment takes longer than anticipated. The current embedded trial evaluates the effectiveness of optimised patient information sheets on recruitment of participants in a falls prevention trial. A three-arm, embedded randomised methodology trial was conducted within the National Institute for Health Research-funded REducing Falls with ORthoses and a Multifaceted podiatry intervention (REFORM) cohort randomised controlled trial. Routine National Health Service podiatry patients over the age of 65 were randomised to receive either the control patient information sheet (PIS) for the host trial or one of two optimised versions, a bespoke user-tested PIS or a template-developed PIS. The primary outcome was the proportion of patients in each group who went on to be randomised to the host trial. Six thousand and nine hundred patients were randomised 1:1:1 into the embedded trial. A total of 193 (2.8%) went on to be randomised into the main REFORM trial (control n = 62, template-developed n = 68; bespoke user-tested n = 63). Information sheet allocation did not improve recruitment to the trial (odds ratios for the three pairwise comparisons: template vs control 1.10 (95% CI 0.77-1.56, p = 0.60); user-tested vs control 1.01 (95% CI 0.71-1.45, p = 0.94); and user-tested vs template 0.92 (95% CI 0.65-1.31, p = 0.65)). This embedded methodology trial has demonstrated limited evidence as to the benefit of using optimised information materials on recruitment and retention rates in the REFORM study. International Standard Randomised Controlled Trials Number registry, ISRCTN68240461 . Registered on 01 July 2011.

A compound herbal preparation (CHP) in the treatment of children with ADHD: a randomized controlled trial.

PubMed

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

2010-11-01

Evaluation of the efficacy of a patented, compound herbal preparation (CHP) in improving attention, cognition, and impulse control in children with ADHD. A randomized, double-blind, placebo-controlled trial. University-affiliated tertiary medical center. 120 children newly diagnosed with ADHD, meeting DSM-IV criteria. Random assignment to the herbal treatment group (n = 80) or control group (placebo; n = 40); 73 patients in the treatment group (91%) and 19 in the control group (48%) completed the 4-month trial. Test of Variables of Attention (TOVA) administered before and after the treatment period; overall score and 4 subscales. The treatment group showed substantial, statistically significant improvement in the 4 subscales and overall TOVA scores, compared with no improvement in the control group, which persisted in an intention-to-treat analysis. The well-tolerated CHP demonstrated improved attention, cognition, and impulse control in the intervention group, indicating promise for ADHD treatment in children.

Importance of Virtual Reality to Virtual Reality Exposure Therapy, Study Design of a Randomized Trial.

PubMed

McLay, Robert N; Baird, Alicia; Murphy, Jennifer; Deal, William; Tran, Lily; Anson, Heather; Klam, Warren; Johnston, Scott

2015-01-01

Post Traumatic Stress Disorder (PTSD) can be a debilitating problem in service members who have served in Iraq or Afghanistan. Virtual Reality Exposure Therapy (VRET) is one of the few interventions demonstrated in randomized controlled trials to be effective for PTSD in this population. There are theoretical reasons to expect that Virtual Reality (VR) adds to the effectiveness of exposure therapy, but there is also added expense and difficulty in using VR. Described is a trial comparing outcomes from VRET and a control exposure therapy (CET) protocol in service members with PTSD.

THE USE OF RANDOMIZED CONTROLLED TRIALS OF IN-HOME DRINKING WATER TREATMENT TO STUDY ENDEMIC WATERBORNE DISEASE

EPA Science Inventory

Randomized trials of water treatment have demonstrated the ability of simple water treatments to significantly reduce the incidence of gastrointestinal illnesses in developing countries where drinking water is of poor quality. Whether or not additional treatment at the tap reduc...

Functional difference between sustained and transient modulations of cognitive control in the simon task: evidence from false alarm responses on no-go trials.

PubMed

Hasegawa, Kunihiro; Takahashi, Shin'ya

2013-01-01

Cognitive control in response compatibility tasks is modulated by the task context. Two types of contextual modulations have been demonstrated; sustained (block-wise) and transient (trial-by-trial). Recent research suggests that these modulations have different underlying mechanisms. This study presents new evidence supporting this claim by comparing false alarm (FA) responses on no-go trials of the Simon task between the sustained and transient contexts. In Experiment 1, the sustained context was manipulated so that a block included a larger number of incongruent trials. Results showed that participants made more FA responses by the hand opposite to the stimulus location. This suggests a generation of response bias in which the task-irrelevant location information is utilized in a reversed manner (i.e., to respond with the right hand to a stimulus presented on the left side and vice versa). Next, Experiment 2 examined the effect of the transient context and found that overall FA rate was lower when a no-go trial was preceded by an incongruent trial than by a congruent trial, whereas such response bias as that shown in Experiment 1 was not demonstrated. This suggests that the transient conflict context enhances inhibition of the task-irrelevant process but does not make the task-irrelevant information actively usable. Based on these results, we propound two types of cognitive control modulations as adaptive behaviors: response biasing based on utilization of the task-irrelevant information under the sustained conflict context and transient enhancement of inhibition of the task-irrelevant process based on the online conflict monitoring.

HIV prevention trial design in an era of effective pre-exposure prophylaxis.

PubMed

Cutrell, Amy; Donnell, Deborah; Dunn, David T; Glidden, David V; Grobler, Anneke; Hanscom, Brett; Stancil, Britt S; Meyer, R Daniel; Wang, Ronnie; Cuffe, Robert L

2017-01-01

Pre-exposure prophylaxis (PrEP) has demonstrated remarkable effectiveness protecting at-risk individuals from HIV-1 infection. Despite this record of effectiveness, concerns persist about the diminished protective effect observed in women compared with men and the influence of adherence and risk behaviors on effectiveness in targeted subpopulations. Furthermore, the high prophylactic efficacy of the first PrEP agent, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), presents challenges for demonstrating the efficacy of new candidates. Trials of new agents would typically require use of non-inferiority (NI) designs in which acceptable efficacy for an experimental agent is determined using pre-defined margins based on the efficacy of the proven active comparator (i.e. TDF/FTC) in placebo-controlled trials. Setting NI margins is a critical step in designing registrational studies. Under- or over-estimation of the margin can call into question the utility of the study in the registration package. The dependence on previous placebo-controlled trials introduces the same issues as external/historical controls. These issues will need to be addressed using trial design features such as re-estimated NI margins, enrichment strategies, run-in periods, crossover between study arms, and adaptive re-estimation of sample sizes. These measures and other innovations can help to ensure that new PrEP agents are made available to the public using stringent standards of evidence.

Effectiveness of an HIV/STD risk-reduction intervention for adolescents when implemented by community-based organizations: a cluster-randomized controlled trial.

PubMed

Jemmott, John B; Jemmott, Loretta S; Fong, Geoffrey T; Morales, Knashawn H

2010-04-01

We evaluated the effectiveness of an HIV/STD risk-reduction intervention when implemented by community-based organizations (CBOs). In a cluster-randomized controlled trial, 86 CBOs that served African American adolescents aged 13 to 18 years were randomized to implement either an HIV/STD risk-reduction intervention whose efficacy has been demonstrated or a health-promotion control intervention. CBOs agreed to implement 6 intervention groups, a random half of which completed 3-, 6-, and 12-month follow-up assessments. The primary outcome was consistent condom use in the 3 months prior to each follow-up assessment, averaged over the follow-up assessments. Participants were 1707 adolescents, 863 in HIV/STD-intervention CBOs and 844 in control-intervention CBOs. HIV/STD-intervention participants were more likely to report consistent condom use (odds ratio [OR] = 1.39; 95% confidence interval [CI] = 1.06, 1.84) than were control-intervention participants. HIV/STD-intervention participants also reported a greater proportion of condom-protected intercourse (beta = 0.06; 95% CI = 0.00, 0.12) than did the control group. This is the first large, randomized intervention trial to demonstrate that CBOs can successfully implement an HIV/STD risk-reduction intervention whose efficacy has been established.

Effectiveness of an HIV/STD Risk-Reduction Intervention for Adolescents When Implemented by Community-Based Organizations: A Cluster-Randomized Controlled Trial

PubMed Central

Jemmott, Loretta S.; Fong, Geoffrey T.; Morales, Knashawn H.

2010-01-01

Objectives. We evaluated the effectiveness of an HIV/STD risk-reduction intervention when implemented by community-based organizations (CBOs). Methods. In a cluster-randomized controlled trial, 86 CBOs that served African American adolescents aged 13 to 18 years were randomized to implement either an HIV/STD risk-reduction intervention whose efficacy has been demonstrated or a health-promotion control intervention. CBOs agreed to implement 6 intervention groups, a random half of which completed 3-, 6-, and 12-month follow-up assessments. The primary outcome was consistent condom use in the 3 months prior to each follow-up assessment, averaged over the follow-up assessments. Results. Participants were 1707 adolescents, 863 in HIV/STD-intervention CBOs and 844 in control-intervention CBOs. HIV/STD-intervention participants were more likely to report consistent condom use (odds ratio [OR] = 1.39; 95% confidence interval [CI] = 1.06, 1.84) than were control-intervention participants. HIV/STD-intervention participants also reported a greater proportion of condom-protected intercourse (β = 0.06; 95% CI = 0.00, 0.12) than did the control group. Conclusions. This is the first large, randomized intervention trial to demonstrate that CBOs can successfully implement an HIV/STD risk-reduction intervention whose efficacy has been established. PMID:20167903

Efficacy of Candida sake CPA-1 formulation for controlling Penicillium expansum decay on pome fruit from different Mediterranean regions.

PubMed

Torres, R; Teixidó, N; Viñas, I; Mari, M; Casalini, L; Giraud, M; Usall, J

2006-11-01

The effectiveness of a formulated product of the yeast Candida sake CPA-1 for controlling postharvest diseases on pome fruits was demonstrated in laboratory, semicommercial, and commercial trials carried out in the major pome fruit producing region of the European Union. First, one wettable powder and seven liquid formulations were tested in laboratory trials that involved two varieties of apples and two varieties of pears. In all cases, an efficacy similar to that of fresh cells was demonstrated in the control of artificial Penicillium expansum infection. After these trials, the formulated product chosen for semicommercial and commercial trials was LF1, a liquid formulation that is particularly suitable for commercial applications. In semicommercial trials, LF1 showed a performance similar to fresh cells in most trials, and the population dynamics of both fresh and formulated cells were quite stable throughout the storage period. This indicates the high viability of C. sake CPA-1 in this formulation and the absence of adverse effects during the formulation of the product, which may significantly affect both its ability to grow on fruit and its antagonistic activity. We evaluated the control of natural infection after applying the formulated product in a commercial drencher in different packinghouses. A significant reduction in the incidence of diseases was observed with a recommended dose of around 10(7) CFU/ml when natural infections were greater than 1%. In general, large quantities of yeast were observed on the surface of unwounded fruits of different pome fruit cultivars. Moreover, populations of this biocontrol agent increased rapidly on fruit surfaces and remained quite stable for a long time under commercial storage conditions. Commercial practices used in packinghouses were therefore successfully applied for this formulated product.

A Web-Based Adolescent Positive Psychology Program in Schools: Randomized Controlled Trial

PubMed Central

Manicavasagar, Vijaya; Batterham, Philip J; Miller, Leonie M; Talbot, Elizabeth; Lum, Alistair

2015-01-01

Background Adolescent mental health is characterized by relatively high rates of psychiatric disorders and low levels of help-seeking behaviors. Existing mental health programs aimed at addressing these issues in adolescents have repeated inconsistent results. Such programs have generally been based on techniques derived from cognitive behavioral therapy, which may not be ideally suited to early intervention among adolescent samples. Positive psychology, which seeks to improve well-being rather than alleviate psychological symptoms, offers an alternative approach. A previous community study of adolescents found that informal engagement in an online positive psychology program for up to 6 weeks yielded significant improvements in both well-being and depression symptoms. However, this approach had not been trialed among adolescents in a structured format and within a school setting. Objective This study examines the feasibility of an online school-based positive psychology program delivered in a structured format over a 6-week period utilizing a workbook to guide students through website content and interactive exercises. Methods Students from four high schools were randomly allocated by classroom to either the positive psychology condition, "Bite Back", or the control condition. The Bite Back condition consisted of positive psychology exercises and information, while the control condition used a series of non-psychology entertainment websites. Both interventions were delivered online for 6 hours over a period of 4-6 weeks during class time. Symptom measures and measures of well-being/flourishing and life satisfaction were administered at baseline and post intervention. Results Data were analyzed using multilevel linear modeling. Both conditions demonstrated reductions in depression, stress, and total symptom scores without any significant differences between the two conditions. Both the Bite Back and control conditions also demonstrated significant improvements in life satisfaction scores post intervention. However, only the control condition demonstrated significant increases in flourishing scores post intervention. Conclusions Results suggest that a structured online positive psychology program administered within the school curriculum was not effective when compared to the control condition. The limitations of online program delivery in school settings including logistic considerations are also relevant to the contradictory findings of this study. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN1261200057831; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362489 (Archived by Webcite at http://www.webcitation.org/6NXmjwfAy). PMID:26220564

Hyperthermia and fever control in brain injury.

PubMed

Badjatia, Neeraj

2009-07-01

Fever in the neurocritical care setting is common and has a negative impact on outcome of all disease types. Meta-analyses have demonstrated that fever at onset and in the acute setting after ischemic brain injury, intracerebral hemorrhage, and cardiac arrest has a negative impact on morbidity and mortality. Data support that the impact of fever is sustained for longer durations after subarachnoid hemorrhage and traumatic brain injury. Recent advances have made eliminating fever and maintaining normothermia feasible. However, there are no prospective randomized trials demonstrating the benefit of fever control in these patient populations, and important questions regarding indications and timing remain. The purpose of this review is to analyze the data surrounding the impact of fever across a range of neurologic injuries to better understand the optimal timing and duration of fever control. Prospective randomized trials are needed to determine whether the beneficial impact of secondary injury prevention is outweighed by the potential risks of prolonged fever control.

Are placebo-controlled trials of creams for athlete's foot still justified?

PubMed

Crawford, F; Harris, R; Williams, H C

2008-09-01

Placebo-controlled trials are useful in identifying effective treatments where none has existed, but their continued use once efficacy is established arguably contravenes ethical standards for medical research. To consider whether sufficient evidence exists to recommend the abandonment of vehicle-controlled studies in trials of topical treatments for athlete's foot. We searched nine electronic databases and bibliographies of review articles as part of an ongoing Cochrane systematic review from 1966 to 2007. Randomized controlled trials (RCTs) using a vehicle control design involving participants with a mycological diagnosis of a dermatophyte infection of the skin of the foot were included. Allylamines, azoles, ciclopiroxolamine, tolnaftate, butenafine and undecanoates were all more effective than vehicle controls. Evidence of the superiority of azole creams over vehicle controls was fairly consistent from 1975 onwards. Data from patients treated with allylamines have shown their superior effects relative to vehicle controls since 1991 for even short-term outcomes. The superiority of allylamines and azoles over vehicle in vehicle-controlled trials has been well established, and data demonstrating this fact have been available since the completion of early RCTs. These preparations are effective and safe, and investigators of RCTs evaluating topical treatments for athlete's foot need to choose potential comparators as control interventions in the light of this knowledge and to consider the ethics of withholding effective treatment from patients who seek treatment for this common foot infection.

Neural substrates of visuomotor learning based on improved feedback control and prediction

PubMed Central

Grafton, Scott T.; Schmitt, Paul; Horn, John Van; Diedrichsen, Jörn

2008-01-01

Motor skills emerge from learning feedforward commands as well as improvements in feedback control. These two components of learning were investigated in a compensatory visuomotor tracking task on a trial-by-trial basis. Between trial learning was characterized with a state-space model to provide smoothed estimates of feedforward and feedback learning, separable from random fluctuations in motor performance and error. The resultant parameters were correlated with brain activity using magnetic resonance imaging. Learning related to the generation of a feedforward command correlated with activity in dorsal premotor cortex, inferior parietal lobule, supplementary motor area and cingulate motor area, supporting a role of these areas in retrieving and executing a predictive motor command. Modulation of feedback control was associated with activity in bilateral posterior superior parietal lobule as well as right ventral premotor cortex. Performance error correlated with activity in a widespread cortical and subcortical network including bilateral parietal, premotor and rostral anterior cingulate cortex as well as the cerebellar cortex. Finally, trial-by-trial changes of kinematics, as measured by mean absolute hand acceleration, correlated with activity in motor cortex and anterior cerebellum. The results demonstrate that incremental, learning dependent changes can be modeled on a trial-by-trial basis and neural substrates for feedforward control of novel motor programs are localized to secondary motor areas. PMID:18032069

Effects of Directed Written Disclosure on Grief and Distress Symptoms among Bereaved Individuals

ERIC Educational Resources Information Center

Lichtenthal, Wendy G.; Cruess, Dean G.

2010-01-01

Bereavement-specific written disclosure trials have generally demonstrated null effects, but these studies have not directed the focus of writing. This randomized controlled trial compared directed writing that focused on either sense-making or benefit-finding, both associated with adjustment to loss, to traditional, non-directed emotional…

Successful Outcomes from a Structured Curriculum Used in the Veterans Affairs Low Vision Intervention Trial

ERIC Educational Resources Information Center

Stelmack, Joan A.; Rinne, Stephen; Mancil, Rickilyn M.; Dean, Deborah; Moran, D'Anna; Tang, X. Charlene; Cummings, Roger; Massof, Robert W.

2008-01-01

A low vision rehabilitation program with a structured curriculum was evaluated in a randomized controlled trial. The treatment group demonstrated large improvements in self-reported visual function (reading, mobility, visual information processing, visual motor skills, and overall). The team approach and the protocols of the treatment program are…

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials.

PubMed

Cooper, Cindy L; Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-04-01

External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

PubMed Central

Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-01-01

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate. PMID:29361833

A review of the ethics of the use of placebo in clinical trials for relapsing-remitting multiple sclerosis therapeutics.

PubMed

Solomon, Andrew J; Bernat, James L

2016-05-01

Randomized placebo-controlled clinical trials have been considered the most rigorous method of evaluating the efficacy of novel treatment interventions. The first effective disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) were approved in the 1990s after a number of pivotal placebo-controlled trials. Since then, the ethics of the continued use of placebo in clinical trials of new DMTs for RRMS has been the subject of repeated policy statements and recommendations by international committees. As further data have accumulated demonstrating a reduction in long-term morbidity and mortality with early initiation of DMT, a growing consensus has emerged that further inclusion of placebo arms in clinical trials of novel RRMS therapies is no longer ethical. Copyright © 2016 Elsevier B.V. All rights reserved.

Pharmacological interventions for self-injurious behaviour in adults with intellectual disabilities: Abridged republication of a Cochrane systematic review.

PubMed

Gormez, A; Rana, F; Varghese, S

2014-07-01

We aimed to determine clinical effectiveness of pharmacological interventions for self-injurious behaviour in adults with intellectual disability. We searched the following databases: CENTRAL; MEDLINE; EMBASE; PsycINFO; CINAHL; SCI; SSCI; Conference Proceedings Citation Index - Science; Conference Proceedings Citation Index - Social Science and Humanities; ZETOC; World Cat .We also searched ClinicalTrials.gov,ICTRP and the reference lists of included trials. We included randomised controlled trials that examined drug interventions versus placebo for self-injurious behaviour. We found five double-blind, placebo-controlled trials, which included a total of 50 people. Four trials compared the effects of naltrexone versus placebo and one trial clomipramine versus placebo. We did not identify any relevant placebo-controlled trials for other drugs. We presented a narrative summary, as meta-analysis was not appropriate due to differences in study designs, differences between interventions and heterogeneous outcome measures. There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating self-injurious behaviour. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo. © The Author(s) 2014.

The face-specific proportion congruency effect: social stimuli as contextual cues.

PubMed

Jiménez-Moya, Gloria; Rodríguez-Bailón, Rosa; Lupiáñez, Juan

2018-06-18

Previous research shows that larger interference is observed in contexts associated with a high proportion of congruent trials than in those associated with a low proportion of congruent trials. Given that one of the most relevant contexts for human beings is social context, researchers have recently explored the possibility that social stimuli could also work as contextual cues for the allocation of attentional control. In fact, it has been shown that individuals use social categories (i.e., men and women) as cues to allocate attentional control. In this work, we go further by showing that individual faces (instead of the social categories they belong to) associated with a high proportion of congruent trials can also lead to larger interference effects compared to individual faces predicting a relatively low proportion of congruent trials. Furthermore, we show that faces associated with a high proportion of congruent trials are more positively evaluated than faces associated with a high proportion of incongruent trials. These results demonstrate that unique human faces are potential contextual cues than can be employed to apply cognitive control when performing an automatic task.

Accounting for sequential trial effects in the flanker task: conflict adaptation or associative priming?

PubMed

Nieuwenhuis, Sander; Stins, John F; Posthuma, Danielle; Polderman, Tinca J C; Boomsma, Dorret I; de Geus, Eco J

2006-09-01

The conflict-control loop theory proposes that the detection of conflict in information processing triggers an increase in cognitive control, resulting in improved performance on the subsequent trial. This theory seems consistent with the robust finding that conflict susceptibility is reduced following correct trials associated with high conflict: the conflict adaptation effect. However, despite providing favorable conditions for eliciting and detecting conflict-triggered performance adjustments, none of the five experiments reported here provide unequivocal evidence of such adjustments. Instead, the results corroborate and extend earlier findings by demonstrating that the conflict adaptation effect, at least in the flanker task, is only present for a specific subset of trial sequences that is characterized by a response repetition. This pattern of results provides strong evidence that the conflict adaptation effect reflects associative stimulus-response priming instead of conflict-driven adaptations in cognitive control.

No pain, no gain: the affective valence of congruency conditions changes following a successful response.

PubMed

Schouppe, Nathalie; Braem, Senne; De Houwer, Jan; Silvetti, Massimo; Verguts, Tom; Ridderinkhof, K Richard; Notebaert, Wim

2015-03-01

The cognitive control theory of Botvinick, Cognitive, Affective, & Behavioral Neuroscience, 7, 356-366 (2007) integrates cognitive and affective control processes by emphasizing the aversive nature of cognitive conflict. Using an affective priming paradigm, we replicate earlier results showing that incongruent trials, relative to congruent trials, are indeed perceived as more aversive (Dreisbach & Fischer, Brain and Cognition, 78(2), 94-98 (2012)). Importantly, however, in two experiments we demonstrate that this effect is reversed following successful responses; correctly responding to incongruent trials engendered relatively more positive affect than correctly responding to congruent trials. The results are discussed in light of a recent computational model by Silvetti, Seurinck, and Verguts, Frontiers in Human Neuroscience, 5:75 (2011) where it is assumed that outcome expectancies are more negative for incongruent trials than congruent trials. Consequently, the intrinsic reward (prediction error) following successful completion is larger for incongruent than congruent trials. These findings divulge a novel perspective on 'cognitive' adaptations to conflict.

Multiplicity of mechanisms govern efficacy of anaerobic soil disinfestation for soil-borne disease control

USDA-ARS?s Scientific Manuscript database

Studies demonstrated that carbon input type influenced control of various fungi, oomycetes and plant parasitic nematodes with anaerobic soil disinfestation (ASD). Findings implicated multiple mechanisms may contribute to the overall level of disease control attained. In strawberry field trials, ASD ...

Effectiveness of mobile technologies delivering Ecological Momentary Interventions for stress and anxiety: a systematic review.

PubMed

Loo Gee, Brendan; Griffiths, Kathleen M; Gulliver, Amelia

2016-01-01

Mobile technologies may be suitable for delivering Ecological Momentary Interventions (EMI) to treat anxiety in real-time. This review aims to synthesize evidence on the effectiveness of EMI for treating anxiety conditions. Four databases and the reference lists of previous studies were searched. A total of 1949 abstracts were double screened for inclusion. Sufficient studies were available to undertake a quantitative meta-analysis on EMIs on generalized anxiety symptoms. The 15 randomized trials and randomized controlled trials examined anxiety (n = 7), stress (n = 3), anxiety and stress (n = 2), panic disorder (n = 2), and social phobia (n = 1). Eight EMIs comprised self-monitoring integrated with therapy modules, seven comprised multimedia content, and three comprised self-monitoring only. The quality of studies presented high risk of biases. Meta-analysis (n = 7) demonstrated that EMIs reduced generalized anxiety compared to control and/or comparison groups (Effect Size (ES) = 0.32, 95% CI, 0.12-0.53). Most EMIs targeting stress were reported effective relative to control as were the two EMIs targeting panic disorders. The EMI targeting social phobia was not effective. EMIs have potential in treating both anxiety and stress. However, few high-quality trials have been conducted for specific anxiety disorders. Further trials are needed to assess the value of EMI technologies for anxiety in enhancing existing treatments. This study found a small significant effect of EMI studies on reducing generalized anxiety. Studies on stress demonstrated EMI was effective compared to control, with the small number of studies on panic and social phobia demonstrating mixed results. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

PubMed Central

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas; Gluud, Christian; Wetterslev, Jørn; Vaag, Allan; Hemmingsen, Bianca

2014-01-01

Objective To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. Design A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. Data sources The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013. Study selection Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. Data extraction Two authors independently assessed studies for inclusion and extracted data. Results 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate. Conclusions There was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control. PMID:25138801

Plasma-Generating Glucose Monitor Accuracy Demonstrated in an Animal Model

PubMed Central

Magarian, Peggy; Sterling, Bernhard

2009-01-01

Introduction Four randomized controlled trials have compared mortality and morbidity of tight glycemic control versus conventional glucose for intensive care unit (ICU) patients. Two trials showed a positive outcome. However, one single-center trial and a large multicenter trial had negative results. The positive trials used accurate portable lab analyzers. The negative trial allowed the use of meters. The portable analyzer measures in filtered plasma, minimizing the interference effects. OptiScan Biomedical Corporation is developing a continuous glucose monitor using centrifuged plasma and mid-infrared spectroscopy for use in ICU medicine. The OptiScanner draws approximately 0.1 ml of blood every 15 min and creates a centrifuged plasma sample. Internal quality control minimizes sample preparation error. Interference adjustment using this technique has been presented at the Society of Critical Care Medicine in separate studies since 2006. Method A good laboratory practice study was conducted on three Yorkshire pigs using a central venous catheter over 6 h while performing a glucose challenge. Matching Yellow Springs Instrument glucose readings were obtained. Results Some 95.7% of the predicted values were in the Clarke Error Grid A zone and 4.3% in the B zone. Of those in the B zone, all were within 3.3% of the A zone boundaries. The coefficient of determination (R2) was 0.993. The coefficient of variance was 5.02%. Animal necropsy and blood panels demonstrated safety. Conclusion The OptiScanner investigational device performed safely and accurately in an animal model. Human studies using the device will begin soon. PMID:20144396

Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.

PubMed

Citrome, Leslie

2016-01-01

Aripiprazole monohydrate (AM) and aripiprazole lauroxil (AL) are two different long-acting injectable formulations of aripiprazole. AM 400 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial, as well as in a double-blind, placebo-controlled, randomized-withdrawal maintenance study, and in two non-inferiority maintenance studies. AL is a prodrug of aripiprazole and available in 441 mg, 662 mg or 882 mg strengths. AL 441 mg and 882 mg administered once monthly demonstrated efficacy in an acute, double-blind, placebo-controlled, randomized clinical trial. The pharmacokinetic profile of AL also led to approval of dosing intervals of every 6 weeks for the 882 mg dose. The overall tolerability profiles of both products are consistent with what is known about oral aripiprazole.

Can a documentary increase help-seeking intentions in men? A randomised controlled trial

PubMed Central

Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

Background We investigated whether a public health intervention—a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality—could increase men’s intentions to seek help for personal and emotional problems. Methods We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Results Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Conclusions Our trial demonstrates the potential for men’s health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. Trial registration number ACTRN12616001169437, Results. PMID:29101215

Self-controlled knowledge of results: age-related differences in motor learning, strategies, and error detection.

PubMed

Carter, Michael J; Patterson, Jae T

2012-12-01

Research has demonstrated that a self-controlled KR schedule is advantageous for motor learning; however, the usefulness of a self-controlled KR context in older adults remains unknown. To address this gap in knowledge, we examined whether (1) the learning benefits of a self-controlled KR schedule are modulated by the age of the learner; (2) practicing in a self-controlled KR context concurrently strengthens the learner's error detection mechanism, and (3) the KR strategy during acquisition changes as a function of practice trials completed and age. As a function of age, participants were quasirandomly assigned to either the self-control or yoked group resulting in four experimental groups (Self-Young, Yoked-Young, Self-Old, and Yoked-Old). The results revealed the Self-Young group: (1) demonstrated superior retention performance than all other groups (p<.05); (2) was more accurate in estimating motor performance than all other groups during retention (p<.05), and (3) self-reported a switch in their strategy for requesting KR during acquisition based on the number of practice trials completed. Collectively, our findings suggest that older adults do not demonstrate the same learning benefits of a self-controlled KR context as younger adults which may be attributed to differences in KR strategies. Copyright © 2012 Elsevier B.V. All rights reserved.

Characteristics of an aerosol photometer while automatically controlling chamber dilution-air flow rate.

PubMed

O'Shaughnessy, P T; Hemenway, D R

2000-10-01

Trials were conducted to determine those factors that affect the accuracy of a direct-reading aerosol photometer when automatically controlling airflow rate within an exposure chamber to regulate airborne dust concentrations. Photometer response was affected by a shift in the aerosol size distribution caused by changes in chamber flow rate. In addition to a dilution effect, flow rate also determined the relative amount of aerosol lost to sedimentation within the chamber. Additional calculations were added to a computer control algorithm to compensate for these effects when attempting to automatically regulate flow based on a proportional-integral-derivative (PID) feedback control algorithm. A comparison between PID-controlled trials and those performed with a constant generator output rate and dilution-air flow rate demonstrated that there was no significant decrease in photometer accuracy despite the many changes in flow rate produced when using PID control. Likewise, the PID-controlled trials produced chamber aerosol concentrations within 1% of a desired level.

Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials.

PubMed

de Labra, Carmen; Guimaraes-Pinheiro, Christyanne; Maseda, Ana; Lorenzo, Trinidad; Millán-Calenti, José C

2015-12-02

Low physical activity has been shown to be one of the most common components of frailty, and interventions have been considered to prevent or reverse this syndrome. The purpose of this systematic review of randomized, controlled trials is to examine the exercise interventions to manage frailty in older people. The PubMed, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched using specific keywords and Medical Subject Headings for randomized, controlled trials published during the period of 2003-2015, which enrolled frail older adults in an exercise intervention program. Studies where frailty had been defined were included in the review. A narrative synthesis approach was performed to examine the results. The Physiotherapy Evidence Database (PEDro scale) was used to assess the methodological quality of the selected studies. Of 507 articles, nine papers met the inclusion criteria. Of these, six included multi-component exercise interventions (aerobic and resistance training not coexisting in the intervention), one included physical comprehensive training, and two included exercises based on strength training. All nine of these trials included a control group receiving no treatment, maintaining their habitual lifestyle or using a home-based low level exercise program. Five investigated the effects of exercise on falls, and among them, three found a positive impact of exercise interventions on this parameter. Six trials reported the effects of exercise training on several aspects of mobility, and among them, four showed enhancements in several measurements of this outcome. Three trials focused on the effects of exercise intervention on balance performance, and one demonstrated enhanced balance. Four trials investigated functional ability, and two showed positive results after the intervention. Seven trials investigated the effects of exercise intervention on muscle strength, and five of them reported increases; three trials investigated the effects of exercise training on body composition, finding improvements in this parameter in two of them; finally, one trial investigated the effects of exercise on frailty using Fried's criteria and found an improvement in this measurement. Exercise interventions have demonstrated improvement in different outcome measurements in frail older adults, however, there were large differences between studies with regard to effect sizes. This systematic review suggested that frail older adults seemed to benefit from exercise interventions, although the optimal program remains unclear. More studies of this topic and with frail populations are needed to select the most favorable exercise program.

Perceptions of Massage Therapists Participating in a Randomized Controlled Trial

PubMed Central

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

2015-01-01

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

Reducing Achievement Gaps in Academic Writing for Latinos and English Learners in Grades 7-12

ERIC Educational Resources Information Center

Olson, Carol Booth; Matuchniak, Tina; Chung, Huy Q.; Stumpf, Rachel; Farkas, George

2017-01-01

This study reports 2 years of findings from a randomized controlled trial designed to replicate and demonstrate the efficacy of an existing, successful professional development program, the Pathway Project, that uses a cognitive strategies approach to text-based analytical writing. Building on an earlier randomized field trial in a large, urban,…

Data Mining and Domain Knowledge: An Exploration of Methods to Advance Medical Research

ERIC Educational Resources Information Center

Engle, Kelley M.

2013-01-01

Researchers in the medical domain consider the double-blind placebo controlled clinical trial the gold standard. The data for these clinical trials are collected for a specifically defined hypothesis and there is very little in the realm of secondary data analyses conducted. The underlying purpose of this work is to demonstrate the value and…

Reliability of Single-Leg Balance and Landing Tests in Rugby Union; Prospect of Using Postural Control to Monitor Fatigue.

PubMed

Troester, Jordan C; Jasmin, Jason G; Duffield, Rob

2018-06-01

The present study examined the inter-trial (within test) and inter-test (between test) reliability of single-leg balance and single-leg landing measures performed on a force plate in professional rugby union players using commercially available software (SpartaMARS, Menlo Park, USA). Twenty-four players undertook test - re-test measures on two occasions (7 days apart) on the first training day of two respective pre-season weeks following 48h rest and similar weekly training loads. Two 20s single-leg balance trials were performed on a force plate with eyes closed. Three single-leg landing trials were performed by jumping off two feet and landing on one foot in the middle of a force plate 1m from the starting position. Single-leg balance results demonstrated acceptable inter-trial reliability (ICC = 0.60-0.81, CV = 11-13%) for sway velocity, anterior-posterior sway velocity, and mediolateral sway velocity variables. Acceptable inter-test reliability (ICC = 0.61-0.89, CV = 7-13%) was evident for all variables except mediolateral sway velocity on the dominant leg (ICC = 0.41, CV = 15%). Single-leg landing results only demonstrated acceptable inter-trial reliability for force based measures of relative peak landing force and impulse (ICC = 0.54-0.72, CV = 9-15%). Inter-test results indicate improved reliability through the averaging of three trials with force based measures again demonstrating acceptable reliability (ICC = 0.58-0.71, CV = 7-14%). Of the variables investigated here, total sway velocity and relative landing impulse are the most reliable measures of single-leg balance and landing performance, respectively. These measures should be considered for monitoring potential changes in postural control in professional rugby union.

Effect of telecare on use of health and social care services: findings from the Whole Systems Demonstrator cluster randomised trial

PubMed Central

Steventon, Adam; Bardsley, Martin; Billings, John; Dixon, Jennifer; Doll, Helen; Beynon, Michelle; Hirani, Shashi; Cartwright, Martin; Rixon, Lorna; Knapp, Martin; Henderson, Catherine; Rogers, Anne; Hendy, Jane; Fitzpatrick, Ray; Newman, Stanton

2013-01-01

Objective: to assess the impact of telecare on the use of social and health care. Part of the evaluation of the Whole Systems Demonstrator trial. Participants and setting: a total of 2,600 people with social care needs were recruited from 217 general practices in three areas in England. Design: a cluster randomised trial comparing telecare with usual care, general practice being the unit of randomisation. Participants were followed up for 12 months and analyses were conducted as intention-to-treat. Data sources: trial data were linked at the person level to administrative data sets on care funded at least in part by local authorities or the National Health Service. Main outcome measures: the proportion of people admitted to hospital within 12 months. Secondary endpoints included mortality, rates of secondary care use (seven different metrics), contacts with general practitioners and practice nurses, proportion of people admitted to permanent residential or nursing care, weeks in domiciliary social care and notional costs. Results: 46.8% of intervention participants were admitted to hospital, compared with 49.2% of controls. Unadjusted differences were not statistically significant (odds ratio: 0.90, 95% CI: 0.75–1.07, P = 0.211). They reached statistical significance after adjusting for baseline covariates, but this was not replicated when adjusting for the predictive risk score. Secondary metrics including impacts on social care use were not statistically significant. Conclusions: telecare as implemented in the Whole Systems Demonstrator trial did not lead to significant reductions in service use, at least in terms of results assessed over 12 months. International Standard Randomised Controlled Trial Number Register ISRCTN43002091. PMID:23443509

Assessing delay and lag in sagittal trunk control using a tracking task.

PubMed

Reeves, N Peter; Luis, Abraham; Chan, Elizabeth C; Sal Y Rosas, Victor G; Tanaka, Martin L

2018-05-17

Slower trunk muscle responses are linked to back pain and injury. Unfortunately, clinical assessments of spine function do not objectively evaluate this important attribute, which reflects speed of trunk control. Speed of trunk control can be parsed into two components: (1) delay, the time it takes to initiate a movement, and (2) lag, the time it takes to execute a movement once initiated. The goal of this study is to demonstrate a new approach to assess delay and lag in trunk control using a simple tracking task. Ten healthy subjects performed four blocks of six trials of trunk tracking in the sagittal plane. Delay and lag were estimated by modeling trunk control for predictable and unpredictable (control mode) trunk movements in flexion and extension (control direction) at movement amplitudes of 2°, 4°, and 6° (control amplitude). The main effect of control mode, direction, and amplitude of movement were compared between trial blocks to assess secondary influencers (e.g., fatigue). Only control mode was consistent across trial blocks with predictable movements being faster than unpredictable for both delay and lag. Control direction and amplitude effects on delay and lag were consistent across the first two trial blocks and less consistent in later blocks. Given the heterogeneity in the presentation of back pain, clinical assessment of trunk control should include different control modes, directions, and amplitudes. To reduce testing time and the influence of fatigue, we recommend six trials to assess trunk control. Copyright © 2018 Elsevier Ltd. All rights reserved.

Explaining the effects of an intervention designed to promote evidence-based diabetes care: a theory-based process evaluation of a pragmatic cluster randomised controlled trial

PubMed Central

Francis, Jillian J; Eccles, Martin P; Johnston, Marie; Whitty, Paula; Grimshaw, Jeremy M; Kaner, Eileen FS; Smith, Liz; Walker, Anne

2008-01-01

Background The results of randomised controlled trials can be usefully illuminated by studies of the processes by which they achieve their effects. The Theory of Planned Behaviour (TPB) offers a framework for conducting such studies. This study used TPB to explore the observed effects in a pragmatic cluster randomised controlled trial of a structured recall and prompting intervention to increase evidence-based diabetes care that was conducted in three Primary Care Trusts in England. Methods All general practitioners and nurses in practices involved in the trial were sent a postal questionnaire at the end of the intervention period, based on the TPB (predictor variables: attitude; subjective norm; perceived behavioural control, or PBC). It focussed on three clinical behaviours recommended in diabetes care: measuring blood pressure; inspecting feet; and prescribing statins. Multivariate analyses of variance and multiple regression analyses were used to explore changes in cognitions and thereby better understand trial effects. Results Fifty-nine general medical practitioners and 53 practice nurses (intervention: n = 55, 41.98% of trial participants; control: n = 57, 38.26% of trial participants) completed the questionnaire. There were no differences between groups in mean scores for attitudes, subjective norms, PBC or intentions. Control group clinicians had 'normatively-driven' intentions (i.e., related to subjective norm scores), whereas intervention group clinicians had 'attitudinally-driven' intentions (i.e., related to attitude scores) for foot inspection and statin prescription. After controlling for effects of the three predictor variables, this group difference was significant for foot inspection behaviour (trial group × attitude interaction, beta = 0.72, p < 0.05; trial group × subjective norm interaction, beta = -0.65, p < 0.05). Conclusion Attitudinally-driven intentions are proposed to be more consistently translated into action than normatively-driven intentions. This proposition was supported by the findings, thus offering an interpretation of the trial effects. This analytic approach demonstrates the potential of the TPB to explain trial effects in terms of different relationships between variables rather than differences in mean scores. This study illustrates the use of theory-based process evaluation to uncover processes underlying change in implementation trials. PMID:19019242

Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy.

PubMed

Fureman, Brandy E; Friedman, Daniel; Baulac, Michel; Glauser, Tracy; Moreno, Jonathan; Dixon-Salazar, Tracy; Bagiella, Emilia; Connor, Jason; Ferry, Jim; Farrell, Kathleen; Fountain, Nathan B; French, Jacqueline A

2017-10-03

The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here. © 2017 American Academy of Neurology.

Challenges and opportunities in SLE clinical trials.

PubMed

van Vollenhoven, Ronald F

2013-09-01

To provide an update on the field of clinical trials in systemic lupus erythematosus (SLE). This review will examine failed and successful clinical trials in SLE in order to draw lessons and determine the optimal ways forward. Over the past decade, many clinical trials in SLE met with limited success, but in the past 2 years several SLE clinical trials have been successful. The two large phase III randomized controlled trials (RCTs) of belimumab achieved their primary endpoints and resulted in food and drug administration and European medicines agency approval of the drug. Characteristics of these trials were, among other things, a very large number of patients (>800 each), compound clinical endpoints, and a flexible design with regards to concomitant medication use. Likewise, large randomized controlled trials with mycophenolate mofetil, although nominally unsuccessful, clearly demonstrated the clinical benefit of this drug in lupus nephritis. Posthoc analyses of several failed trials involving abatacept and rituximab revealed design elements and/or outcomes that might have changed the outcomes of these studies. Many smaller trials have also been reported, in some instances with surprisingly positive results. An improved understanding of specific design features in SLE clinical trials combined with robust outcomes will make it possible more effectively to design and conduct clinical trials in SLE.

More than just tapping: index finger-tapping measures procedural learning in schizophrenia.

PubMed

Da Silva, Felipe N; Irani, Farzin; Richard, Jan; Brensinger, Colleen M; Bilker, Warren B; Gur, Raquel E; Gur, Ruben C

2012-05-01

Finger-tapping has been widely studied using behavioral and neuroimaging paradigms. Evidence supports the use of finger-tapping as an endophenotype in schizophrenia, but its relationship with motor procedural learning remains unexplored. To our knowledge, this study presents the first use of index finger-tapping to study procedural learning in individuals with schizophrenia or schizoaffective disorder (SCZ/SZA) as compared to healthy controls. A computerized index finger-tapping test was administered to 1169 SCZ/SZA patients (62% male, 88% right-handed), and 689 healthy controls (40% male, 93% right-handed). Number of taps per trial and learning slopes across trials for the dominant and non-dominant hands were examined for motor speed and procedural learning, respectively. Both healthy controls and SCZ/SZA patients demonstrated procedural learning for their dominant hand but not for their non-dominant hand. In addition, patients showed a greater capacity for procedural learning even though they demonstrated more variability in procedural learning compared to healthy controls. Left-handers of both groups performed better than right-handers and had less variability in mean number of taps between non-dominant and dominant hands. Males also had less variability in mean tap count between dominant and non-dominant hands than females. As expected, patients had a lower mean number of taps than healthy controls, males outperformed females and dominant-hand trials had more mean taps than non-dominant hand trials in both groups. The index finger-tapping test can measure both motor speed and procedural learning, and motor procedural learning may be intact in SCZ/SZA patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Continuous Glucose Monitoring: Impact on Hypoglycemia.

PubMed

van Beers, Cornelis A J; DeVries, J Hans

2016-11-01

The necessity of strict glycemic control is unquestionable. However, hypoglycemia remains a major limiting factor in achieving satisfactory glucose control, and evidence is mounting to show that hypoglycemia is not benign. Over the past decade, evidence has consistently shown that real-time continuous glucose monitoring improves glycemic control in terms of lowering glycated hemoglobin levels. However, real-time continuous glucose monitoring has not met the expectations of the diabetes community with regard to hypoglycemia prevention. The earlier trials did not demonstrate any effect on either mild or severe hypoglycemia and the effect of real-time continuous glucose monitoring on nocturnal hypoglycemia was often not reported. However, trials specifically designed to reduce hypoglycemia in patients with a high hypoglycemia risk have demonstrated a reduction in hypoglycemia, suggesting that real-time continuous glucose monitoring can prevent hypoglycemia when it is specifically used for that purpose. Moreover, the newest generation of diabetes technology currently available commercially, namely sensor-augmented pump therapy with a (predictive) low glucose suspend feature, has provided more convincing evidence for hypoglycemia prevention. This article provides an overview of the hypoglycemia outcomes of randomized controlled trials that investigate the effect of real-time continuous glucose monitoring alone or sensor-augmented pump therapy with a (predictive) low glucose suspend feature. Furthermore, several possible explanations are provided why trials have not shown a reduction in severe hypoglycemia. In addition, existing evidence is presented of real-time continuous glucose monitoring in patients with impaired awareness of hypoglycemia who have the highest risk of severe hypoglycemia. © 2016 Diabetes Technology Society.

Continuous Glucose Monitoring

PubMed Central

van Beers, Cornelis A. J.; DeVries, J. Hans

2016-01-01

The necessity of strict glycemic control is unquestionable. However, hypoglycemia remains a major limiting factor in achieving satisfactory glucose control, and evidence is mounting to show that hypoglycemia is not benign. Over the past decade, evidence has consistently shown that real-time continuous glucose monitoring improves glycemic control in terms of lowering glycated hemoglobin levels. However, real-time continuous glucose monitoring has not met the expectations of the diabetes community with regard to hypoglycemia prevention. The earlier trials did not demonstrate any effect on either mild or severe hypoglycemia and the effect of real-time continuous glucose monitoring on nocturnal hypoglycemia was often not reported. However, trials specifically designed to reduce hypoglycemia in patients with a high hypoglycemia risk have demonstrated a reduction in hypoglycemia, suggesting that real-time continuous glucose monitoring can prevent hypoglycemia when it is specifically used for that purpose. Moreover, the newest generation of diabetes technology currently available commercially, namely sensor-augmented pump therapy with a (predictive) low glucose suspend feature, has provided more convincing evidence for hypoglycemia prevention. This article provides an overview of the hypoglycemia outcomes of randomized controlled trials that investigate the effect of real-time continuous glucose monitoring alone or sensor-augmented pump therapy with a (predictive) low glucose suspend feature. Furthermore, several possible explanations are provided why trials have not shown a reduction in severe hypoglycemia. In addition, existing evidence is presented of real-time continuous glucose monitoring in patients with impaired awareness of hypoglycemia who have the highest risk of severe hypoglycemia. PMID:27257169

Effects of Fructans from Mexican Agave in Newborns Fed with Infant Formula: A Randomized Controlled Trial.

PubMed

López-Velázquez, Gabriel; Parra-Ortiz, Minerva; Mora, Ignacio De la Mora-De la; García-Torres, Itzhel; Enríquez-Flores, Sergio; Alcántara-Ortigoza, Miguel Angel; Angel, Ariadna González-Del; Velázquez-Aragón, José; Ortiz-Hernández, Rosario; Cruz-Rubio, José Manuel; Villa-Barragán, Pablo; Jiménez-Gutiérrez, Carlos; Gutiérrez-Castrellón, Pedro

2015-10-29

The importance of prebiotics consumption is increasing all over the world due to their beneficial effects on health. Production of better prebiotics from endemic plants raises possibilities to enhance nutritional effects in vulnerable population groups. Fructans derived from Agave Plant have demonstrated their safety and efficacy as prebiotics in animal models. Recently, the safety in humans of two fructans obtained from Agave tequilana (Metlin(®) and Metlos(®)) was demonstrated. This study aimed to demonstrate the efficacy as prebiotics of Metlin(®) and Metlos(®) in newborns of a randomized, double blind, controlled trial with a pilot study design. Biological samples were taken at 20 ± 7 days, and three months of age from healthy babies. Outcomes of efficacy include impact on immune response, serum ferritin, C-reactive protein, bone metabolism, and gut bacteria changes. There were differences statistically significant for the groups of infants fed only with infant formula and with formula enriched with Metlin(®) and Metlos(®). Our results support the efficacy of Metlin(®) and Metlos(®) as prebiotics in humans, and stand the bases to recommend their consumption. ClinicalTrials.gov, NCT 01251783.

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.

Challenges in randomized controlled trials and emerging multiple sclerosis therapeutics.

PubMed

Huang, DeRen

2015-12-01

The remarkable global development of disease-modifying therapies (DMTs) specific for multiple sclerosis (MS) has significantly reduced the frequency of relapse, slowed the progression of disability, and improved the quality of life in patients with MS. With increasing numbers of approved DMTs, neurologists in North America and Europe are able to present multiple treatment options to their patients to achieve a better therapeutic outcome, and in many cases, no evidence of disease activity. MS patients have improved accessibility to various DMTs at no or minimal out-of-pocket cost. The ethical guidelines defined by the Edinburgh revision of the Declaration of Helsinki strongly discourage the use of placebo control groups in modern MS clinical trials. The use of an active comparator control group increases the number of participants in each group that is essential to achieve statistical significance, thus further increasing the difficulty of completing randomized controlled trials (RCTs) for the development of new MS therapies. There is evidence of a high prevalence of MS and a large number of patients in Asia. The belief of the existence of Asian types of MS that are distinct from Western types, and regulatory policies are among the reasons why DMTs are limited in most Asian countries. Lack of access to approved DMTs provides a good opportunity for clinical trials that are designed for the development of new MS therapies. Recently, data from RCTs have demonstrated excellent recruitment of participants and the completion of multi-nation and single-nation MS trials within this region. Recent studies using the McDonald MS diagnostic criteria carefully excluded patients with neuromyelitis optica (NMO) and NMO spectrum disorder, and demonstrated that patients with MS in Asia have clinical characteristics and treatment responses similar to those in Western countries.

Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder.

PubMed

Breech, Lesley L; Braverman, Paula K

2010-08-09

Premenstrual dysphoric disorder (PMDD) is estimated to affect 3%-8% of reproductive age women. Multiple therapeutic modalities have been evaluated with varying efficacy for the associated somatic and mood symptoms. The majority of older studies had shown that oral contraceptive pills (OCs) were most effective for the physical symptoms. However, newer OCs containing a novel progestin, drospirenone, have shown promise in alleviating both the somatic and affective/behavioral symptoms. This progestin, which is a derivative of spironolactone, has both antimineralocorticoid and antiandrogenic activity. A 24/4 formulation containing 20 μg of ethinyl estradiol has been found effective in randomized double-blind placebo-controlled trials utilizing established scales documenting symptoms associated with PMDD. Multiple studies have shown that drospirenone-containing OCs are safe without evidence of clinically adverse effects on carbohydrate metabolism, lipids, blood pressure, weight, serum potassium or increased thrombotic events compared to other low dose OCs. In addition, significant improvements have been demonstrated in acne, hirsutism, and fluid retention symptoms. Several open label studies demonstrated good patient compliance and reported satisfaction with the method. Because of the significant placebo effect demonstrated in the blinded placebo-controlled trials, additional large randomized placebo-controlled trials are needed to confirm the efficacy of the drospirenone OCs in the treatment of PMDD. However, this OC formulation appears to be a promising therapeutic modality.

Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder

PubMed Central

Breech, Lesley L; Braverman, Paula K

2010-01-01

Premenstrual dysphoric disorder (PMDD) is estimated to affect 3%–8% of reproductive age women. Multiple therapeutic modalities have been evaluated with varying efficacy for the associated somatic and mood symptoms. The majority of older studies had shown that oral contraceptive pills (OCs) were most effective for the physical symptoms. However, newer OCs containing a novel progestin, drospirenone, have shown promise in alleviating both the somatic and affective/behavioral symptoms. This progestin, which is a derivative of spironolactone, has both antimineralocorticoid and antiandrogenic activity. A 24/4 formulation containing 20 μg of ethinyl estradiol has been found effective in randomized double-blind placebo-controlled trials utilizing established scales documenting symptoms associated with PMDD. Multiple studies have shown that drospirenone-containing OCs are safe without evidence of clinically adverse effects on carbohydrate metabolism, lipids, blood pressure, weight, serum potassium or increased thrombotic events compared to other low dose OCs. In addition, significant improvements have been demonstrated in acne, hirsutism, and fluid retention symptoms. Several open label studies demonstrated good patient compliance and reported satisfaction with the method. Because of the significant placebo effect demonstrated in the blinded placebo-controlled trials, additional large randomized placebo-controlled trials are needed to confirm the efficacy of the drospirenone OCs in the treatment of PMDD. However, this OC formulation appears to be a promising therapeutic modality. PMID:21072278

Can a documentary increase help-seeking intentions in men? A randomised controlled trial.

PubMed

King, Kylie Elizabeth; Schlichthorst, Marisa; Spittal, Matthew J; Phelps, Andrea; Pirkis, Jane

2018-01-01

We investigated whether a public health intervention-a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality-could increase men's intentions to seek help for personal and emotional problems. We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Our trial demonstrates the potential for men's health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. ACTRN12616001169437, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pharmacotherapy for trichotillomania.

PubMed

Rothbart, Rachel; Amos, Taryn; Siegfried, Nandi; Ipser, Jonathan C; Fineberg, Naomi; Chamberlain, Samuel R; Stein, Dan J

2013-11-08

Trichotillomania (TTM) (hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. The effect of medication on trichotillomania has not been systematically evaluated. To assess the effects of medication for trichotillomania in adults compared with placebo or other active agents. We searched the Cochrane Central Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register (to 31 July 2013), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years); EMBASE (1974 to date); MEDLINE (1950 to date) and PsycINFO (1967 to date). Two review authors identified relevant trials by assessing the abstracts of all possible studies. We selected randomised controlled trials (RCTs) of a medication versus placebo or active agent for TTM in adults. Two review authors independently performed the data extraction and 'Risk of bias' assessments, and disagreements were resolved through discussion with a third review author. Primary outcomes included the mean difference (MD) in reduction of trichotillomania symptoms on a continuous measure of trichotillomania symptom severity, and the risk ratio (RR) of the clinical response based on a dichotomous measure, with 95% confidence intervals (CIs). We identified eight studies with a total of 204 participants and a mean sample size of 25. All trials were single-centre trials, and participants seen on an outpatient basis. Seven studies compared medication and placebo (n = 184); one study compared medication and another active agent (n = 13). Duration of the studies was six to twelve weeks. Meta-analysis was not undertaken because of the methodological heterogeneity of the trials. The studies did not employ intention-to-treat analyses and were at a high risk of attrition bias. Adverse events were not well-documented in the studies.None of the three studies of selective serotonin reuptake inhibitors (SSRIs) demonstrated strong evidence of a treatment effect on any of the outcomes of interest. The unpublished naltrexone study did not provide strong evidence of a treatment effect. Two studies, an olanzapine study and a N-acetylcysteine (NAC) study, reported statistically significant treatment effects. One study of clomipramine demonstrated a treatment effect on two out of three measures of response to treatment. No particular medication class definitively demonstrates efficacy in the treatment of trichotillomania. Preliminary evidence suggests treatment effects of clomipramine, NAC and olanzapine based on three individual trials, albeit with very small sample sizes.

The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics.

PubMed

Garner, Alan A; Fearnside, Michael; Gebski, Val

2013-09-14

The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. ClinicalTrials.gov: NCT00112398.

Innovative strategies for early clinical R&D.

PubMed

Butz, Robert F; Morelli, Gaetano

2008-01-01

Developments in translational medicine and regulatory initiatives associated with the FDA's Critical Path Initiative are creating new opportunities for innovation in early clinical R&D. The introduction of the exploratory IND process allows small, 'phase 0' clinical trials to be conducted prior to traditional phase I trials - sometimes requiring considerably less chemistry, manufacturing and controls, or preclinical support. Phase 0 clinical trials involving subtherapeutic, yet pharmacologically active, dose levels can provide an early demonstration of clinical proof of concept; such demonstration is of particular importance to small pharmaceutical and early-stage biotechnology companies. However, these opportunities for rapid entry into the clinic must be balanced by a consideration of the unique risks associated with first-in-human clinical trials, and by accounting for public concerns regarding drug safety in general. This feature review discusses how innovative clinical strategies can be used effectively in early drug development.

A Web-Based Adolescent Positive Psychology Program in Schools: Randomized Controlled Trial.

PubMed

Burckhardt, Rowan; Manicavasagar, Vijaya; Batterham, Philip J; Miller, Leonie M; Talbot, Elizabeth; Lum, Alistair

2015-07-28

Adolescent mental health is characterized by relatively high rates of psychiatric disorders and low levels of help-seeking behaviors. Existing mental health programs aimed at addressing these issues in adolescents have repeated inconsistent results. Such programs have generally been based on techniques derived from cognitive behavioral therapy, which may not be ideally suited to early intervention among adolescent samples. Positive psychology, which seeks to improve well-being rather than alleviate psychological symptoms, offers an alternative approach. A previous community study of adolescents found that informal engagement in an online positive psychology program for up to 6 weeks yielded significant improvements in both well-being and depression symptoms. However, this approach had not been trialed among adolescents in a structured format and within a school setting. This study examines the feasibility of an online school-based positive psychology program delivered in a structured format over a 6-week period utilizing a workbook to guide students through website content and interactive exercises. Students from four high schools were randomly allocated by classroom to either the positive psychology condition, "Bite Back", or the control condition. The Bite Back condition consisted of positive psychology exercises and information, while the control condition used a series of non-psychology entertainment websites. Both interventions were delivered online for 6 hours over a period of 4-6 weeks during class time. Symptom measures and measures of well-being/flourishing and life satisfaction were administered at baseline and post intervention. Data were analyzed using multilevel linear modeling. Both conditions demonstrated reductions in depression, stress, and total symptom scores without any significant differences between the two conditions. Both the Bite Back and control conditions also demonstrated significant improvements in life satisfaction scores post intervention. However, only the control condition demonstrated significant increases in flourishing scores post intervention. Results suggest that a structured online positive psychology program administered within the school curriculum was not effective when compared to the control condition. The limitations of online program delivery in school settings including logistic considerations are also relevant to the contradictory findings of this study. Australian New Zealand Clinical Trials Registry: ACTRN1261200057831; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362489 (Archived by Webcite at http://www.webcitation.org/6NXmjwfAy).

40 CFR 266.104 - Standards to control organic emissions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... HAZARDOUS WASTE MANAGEMENT FACILITIES Hazardous Waste Burned in Boilers and Industrial Furnaces § 266.104...) of this section, a boiler or industrial furnace burning hazardous waste must achieve a destruction... demonstrate conformance with this requirement, 99.99% DRE must be demonstrated during a trial burn for each...

40 CFR 266.104 - Standards to control organic emissions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... HAZARDOUS WASTE MANAGEMENT FACILITIES Hazardous Waste Burned in Boilers and Industrial Furnaces § 266.104...) of this section, a boiler or industrial furnace burning hazardous waste must achieve a destruction... demonstrate conformance with this requirement, 99.99% DRE must be demonstrated during a trial burn for each...

40 CFR 266.104 - Standards to control organic emissions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... HAZARDOUS WASTE MANAGEMENT FACILITIES Hazardous Waste Burned in Boilers and Industrial Furnaces § 266.104...) of this section, a boiler or industrial furnace burning hazardous waste must achieve a destruction... demonstrate conformance with this requirement, 99.99% DRE must be demonstrated during a trial burn for each...

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.

PubMed

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas; Gluud, Christian; Wetterslev, Jørn; Lund, Søren Søgaard; Vaag, Allan; Hemmingsen, Bianca

2014-08-19

To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013. Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. Two authors independently assessed studies for inclusion and extracted data. 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate. There was no significant effect towards improved all-cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control. 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.

The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics

PubMed Central

2013-01-01

Background The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. Methods This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Results Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. Conclusion This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. Trial Registration ClinicalTrials.gov: NCT00112398 PMID:24034628

Increasing instructional efficiency by presenting additional stimuli in learning trials for children with autism spectrum disorders.

PubMed

Vladescu, Jason C; Kodak, Tiffany M

2013-12-01

The current study examined the effectiveness and efficiency of presenting secondary targets within learning trials for 4 children with an autism spectrum disorder. Specifically, we compared 4 instructional conditions using a progressive prompt delay. In 3 conditions, we presented secondary targets in the antecedent or consequence portion of learning trials, or in the absence of prompts and reinforcement. In the fourth condition (control), we did not include secondary targets in learning trials. Results replicate and extend previous research by demonstrating that the majority of participants acquired secondary targets presented in the antecedent and consequent events of learning trials. © Society for the Experimental Analysis of Behavior.

Herbal medicine for low back pain: a Cochrane review.

PubMed

Gagnier, Joel J; van Tulder, Maurits W; Berman, Brian; Bombardier, Claire

2007-01-01

A systematic review of randomized controlled trials. To determine the effectiveness of herbal medicine compared with placebo, no intervention, or "standard/accepted/conventional treatments" for nonspecific low back pain. Low back pain is a common condition and a substantial economic burden in industrialized societies. A large proportion of patients with chronic low back pain use complementary and alternative medicine (CAM) and/or visit CAM practitioners. Several herbal medicines have been purported for use in low back pain. The following databases were searched: Medline (1966 to April 2003), Embase (1980 to April 2003), Cochrane Controlled Trials Register (Issue 1, 2003), and Cochrane Complementary Medicine (CM) field Trials Register. Additionally, reference lists in review articles, guidelines, and in the retrieved trials were checked. Randomized controlled trials (RCTs), using adults (>18 years of age) suffering from acute, subacute, or chronic nonspecific low back pain. Types of interventions included herbal medicines defined as a plant that is used for medicinal purposes in any form. Primary outcome measures were pain and function. Two reviewers (J.J.G. and M.W.T.) conducted electronic searches in all databases. One reviewer (J.J.G.) contacted content experts and acquired relevant citations. Authors, title, subject headings, publication type, and abstract of the isolated studies were downloaded or a hard copy was retrieved. Methodologic quality and clinical relevance were assessed separately by two individuals (J.J.G. and M.W.T.). Disagreements were resolved by consensus. Ten trials were included in this review. Two high-quality trials utilizing Harpagophytum procumbens (Devil's claw) found strong evidence for short-term improvements in pain and rescue medication for daily doses standardized to 50 mg or 100 mg harpagoside with another high-quality trial demonstrating relative equivalence to 12.5 mg per day of rofecoxib. Two moderate-quality trials utilizing Salix alba (White willow bark) found moderate evidence for short-term improvements in pain and rescue medication for daily doses standardized to 120 mg or 240 mg salicin with an additional trial demonstrating relative equivalence to 12.5 mg per day of rofecoxib. Three low-quality trials using Capsicum frutescens (Cayenne) using various topical preparations found moderate evidence for favorable results against placebo and one trial found equivalence to a homeopathic ointment. Harpagophytum procumbens, Salix alba, and Capsicum frutescens seem to reduce pain more than placebo. Additional trials testing these herbal medicines against standard treatments will clarify their equivalence in terms of efficacy. The quality of reporting in these trials was generally poor; thus, trialists should refer to the CONSORT statement in reporting clinical trials of herbal medicines.

Does tight heart rate control improve beta-blocker efficacy? An updated analysis of the noncardiac surgical randomized trials.

PubMed

Beattie, W Scott; Wijeysundera, Duminda N; Karkouti, Keyvan; McCluskey, Stuart; Tait, Gordon

2008-04-01

Recent meta-analyses assessing the efficacy of perioperative beta-blockade trials have failed to show a reduction in postoperative morbidity and mortality. Tight control of heart rate (HR) has been suggested to improve these outcomes. Meta-analyses have not considered the influence of tight HR control on the efficacy of perioperative beta-blockade. Using previously published search strategies, we identified all randomized trials evaluating perioperative beta-blockers after noncardiac surgery. This search yielded 10 trials with 2176 patients. We used the data from these studies to correlate measures of HR control with major postoperative outcomes, primarily in-hospital myocardial infarction (MI). Odds ratio (OR) and 95% confidence intervals (CI) were calculated, and metaregression was performed correlating measures of HR control with MI. The combined results of all studies did not show a significant cardioprotective effect of beta-blockers, with considerable heterogeneity among the studies (OR = 0.76; 95% CI = 0.4-1.4; P = 0.38 heterogeneity: I(2) = 34%). However, grouping the trials on the basis of maximal HR showed that trials where the estimated maximal HR was <100 bpm were associated with cardioprotection (OR = 0.23; 95% CI = 0.08-0.65; P = 0.005) whereas trials where the estimated maximal HR was >100 bpm did not demonstrate cardioprotection (OR = 1.17; 95% CI = 0.79-1.80; P = 0.43) with no heterogeneity. Moreover, metaregression of the HR response to beta-blockade against the log OR of postoperative MI demonstrated a linear association between the effect of beta-blockade on the mean, maximal, and variation in HR and the OR of an MI (r(2) = 0.63; P < 0.001) where a larger effect of beta-blockers on HR was associated with a decreased incidence of postoperative MI. Across all studies, beta-blockade resulted in a reduction in postoperative HR (weighted mean difference: 8.6 bpm; 95% CI = -9.6 to -7.6; I(2) = 85.3%) with considerable heterogeneity. This large heterogeneity in HR response to beta-blockade was found to be related, in part, to the type of beta-blocker, specifically, metoprolol, and the concomitant use of calcium channel blockers. Calcium channel blocker use and beta-blockers other than metoprolol resulted in more effective control of HR. There was wide variability in the HR response to beta-blockade. Twenty-five percent of patients receiving beta-blockers had episodes when the HRs were more than 100 bpm, although 15% of placebo patients also had bradycardia, which would have required a dose reduction had they been administered beta-blockers. Finally, this analysis found that perioperative beta-blockade was associated with an increased incidence of bradycardia (OR = 3.49; 95% CI = 2.4-5.9) and congestive heart failure (OR = 1.68; 95% CI = 1.00-2.8). The trials that achieve the most effective control of HR are associated with a reduced incidence of postoperative MI, suggesting that effective control of HR is important for achieving cardioprotection. Second, this analysis demonstrates that administration of beta-blockers does not reliably decrease HRs in all patients, and may be associated with increased side effects. Judicious use of combination therapy with other drugs may be necessary to achieve effective postoperative control of HR.

Evidence for interaction between the stop signal and the Stroop task conflict.

PubMed

Kalanthroff, Eyal; Goldfarb, Liat; Henik, Avishai

2013-04-01

Performance of the Stroop task reflects two conflicts--informational (between the incongruent word and ink color) and task (between relevant color naming and irrelevant word reading). The task conflict is usually not visible, and is only seen when task control is damaged. Using the stop-signal paradigm, a few studies demonstrated longer stop-signal reaction times for incongruent trials than for congruent trials. This indicates interaction between stopping and the informational conflict. Here we suggest that "zooming in" on task-control failure trials will reveal another interaction--between stopping and task conflict. To examine this suggestion, we combined stop-signal and Stroop tasks in the same experiment. When participants' control failed and erroneous responses to a stop signal occurred, a reverse facilitation emerged in the Stroop task (Experiment 1) and this was eliminated using methods that manipulated the emergence of the reverse facilitation (Experiment 2). Results from both experiments were replicated when all stimuli were used in the same task (Experiment 3). In erroneous response trials, only the task conflict increased, not the informational conflict. These results indicate that task conflict and stop-signal inhibition share a common control mechanism that is dissociable from the control mechanism activated by the informational conflict.

Effectiveness of Treatment Approaches for Children and Adolescents with Reading Disabilities: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Galuschka, Katharina; Ise, Elena; Krick, Kathrin; Schulte-Körne, Gerd

2014-01-01

Children and adolescents with reading disabilities experience a significant impairment in the acquisition of reading and spelling skills. Given the emotional and academic consequences for children with persistent reading disorders, evidence-based interventions are critically needed. The present meta-analysis extracts the results of all available randomized controlled trials. The aims were to determine the effectiveness of different treatment approaches and the impact of various factors on the efficacy of interventions. The literature search for published randomized-controlled trials comprised an electronic search in the databases ERIC, PsycINFO, PubMed, and Cochrane, and an examination of bibliographical references. To check for unpublished trials, we searched the websites clinicaltrials.com and ProQuest, and contacted experts in the field. Twenty-two randomized controlled trials with a total of 49 comparisons of experimental and control groups could be included. The comparisons evaluated five reading fluency trainings, three phonemic awareness instructions, three reading comprehension trainings, 29 phonics instructions, three auditory trainings, two medical treatments, and four interventions with coloured overlays or lenses. One trial evaluated the effectiveness of sunflower therapy and another investigated the effectiveness of motor exercises. The results revealed that phonics instruction is not only the most frequently investigated treatment approach, but also the only approach whose efficacy on reading and spelling performance in children and adolescents with reading disabilities is statistically confirmed. The mean effect sizes of the remaining treatment approaches did not reach statistical significance. The present meta-analysis demonstrates that severe reading and spelling difficulties can be ameliorated with appropriate treatment. In order to be better able to provide evidence-based interventions to children and adolescent with reading disabilities, research should intensify the application of blinded randomized controlled trials. PMID:24587110

Enhancing the parent-child relationship: a Hong Kong community-based randomized controlled trial.

PubMed

Fabrizio, Cecilia S; Stewart, Sunita M; Ip, Alison K Y; Lam, Tai Hing

2014-02-01

Adolescence is a critical risk period for negative academic and behavioral outcomes, but a strong parent-child relationship can be a powerful protective factor. Our previous pilot of an academic-community agency collaborative randomized controlled trial (RCT) demonstrated initial evidence of benefit for a parenting intervention with preadolescents in Hong Kong. The present RCT assessed the effect of brief training in positive discipline parenting skills on parental satisfaction with the parent-child relationship. A community sample of 461 Hong Kong Chinese parents of children aged 10-13 years were randomized to (a) the Harmony@Home intervention, (b) an attention control, or (c) a third active intervention that shared the control group. Participants were followed for 12 months and multiple methods of assessment were used. Compared with the control group, the Harmony@Home group reported an increase in the primary outcome of satisfaction with the parent-child relationship at 3 months' postintervention. Although results are mixed, this study demonstrates how a culturally adaptive community intervention can improve the parental behaviors that serve as protective factors against negative academic and behavioral outcomes for Chinese adolescents.

The Effects of Coach Training on Fear of Failure in Youth Swimmers: A Latent Growth Curve Analysis from a Randomized, Controlled Trial

ERIC Educational Resources Information Center

Conroy, David E.; Coatsworth, Douglas J.

2004-01-01

The present study was a randomized trial of the efficacy of psychosocial and injury prevention-based coach training programs for reducing fear of failure (FF) among youth swimmers aged 7 to 18 years. Results revealed that (a) psychosocial training increased coaches' use of reward/reinforcement, (b) the FF measure demonstrated strong factorial…

Design of clinical trials involving multiple hypothesis tests with a common control.

PubMed

Schou, I Manjula; Marschner, Ian C

2017-07-01

Randomized clinical trials comparing several treatments to a common control are often reported in the medical literature. For example, multiple experimental treatments may be compared with placebo, or in combination therapy trials, a combination therapy may be compared with each of its constituent monotherapies. Such trials are typically designed using a balanced approach in which equal numbers of individuals are randomized to each arm, however, this can result in an inefficient use of resources. We provide a unified framework and new theoretical results for optimal design of such single-control multiple-comparator studies. We consider variance optimal designs based on D-, A-, and E-optimality criteria, using a general model that allows for heteroscedasticity and a range of effect measures that include both continuous and binary outcomes. We demonstrate the sensitivity of these designs to the type of optimality criterion by showing that the optimal allocation ratios are systematically ordered according to the optimality criterion. Given this sensitivity to the optimality criterion, we argue that power optimality is a more suitable approach when designing clinical trials where testing is the objective. Weighted variance optimal designs are also discussed, which, like power optimal designs, allow the treatment difference to play a major role in determining allocation ratios. We illustrate our methods using two real clinical trial examples taken from the medical literature. Some recommendations on the use of optimal designs in single-control multiple-comparator trials are also provided. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical significance of tumor necrosis factor-α inhibitors in the treatment of sciatica: a systematic review and meta-analysis.

PubMed

Wang, Yun Fu; Chen, Ping You; Chang, Wei; Zhu, Fi Qi; Xu, Li Li; Wang, Song Lin; Chang, Li Ying; Luo, Jie; Liu, Guang Jian

2014-01-01

Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica. Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria. Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065). The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.

Pilot study demonstrating effectiveness of targeted education to improve informed consent understanding in AIDS clinical trials.

PubMed

Sengupta, Sohini; Lo, Bernard; Strauss, Ronald P; Eron, Joseph; Gifford, Allen L

2011-11-01

Assessing and improving informed consent understanding is equally important as obtaining consent from participants in clinical trial research, but developing interventions to target gaps in participants' informed consent understanding remains a challenge. We used a randomized controlled study design to pilot test an educational intervention to improve actual informed consent understanding of new enrollees in the Adult AIDS Clinical Trial Group (AACTG). Questionnaires were administered to 24 enrollees to assess their baseline understanding on eight elements of informed consent associated with AIDS clinical trials. Enrollees who scored 18/21(85%) or less were randomly assigned to in-person, targeted education (intervention), or delayed education (control). Two follow-up assessments were administered. Repeated measures ANOVA was performed to determine intervention effectiveness in improving actual informed consent understanding over time. Actual understanding improved at the immediate post-intervention time point with a significant score difference of 2.5 when comparing the intervention and delayed groups. In addition, there was a significant score difference of 3.2 when comparing baseline to three-month follow-up for the two groups, suggesting a statistically significant intervention effect to improve actual understanding of the basic elements of informed consent. The findings demonstrated that one-time targeted education can improve actual informed consent understanding one week after the intervention, but retention of these concepts may require periodic monitoring to ensure comprehension throughout the course of a clinical trial.

[Treatment-resistant anxiety disorders: A literature review of drug therapy strategies].

PubMed

Ammar, G; Naja, W J; Pelissolo, A

2015-06-01

Anxiety disorders are widespread psychiatric conditions with significant social and professional disability, poor quality of life, an increased risk of suicide, and frequent attendance of medical services. Serotonin reuptake inhibitors (SRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) have demonstrated a rather robust efficacy for the treatment of most of anxiety disorders. Nevertheless a substantial number of patients are resistant or still suffer from residual symptoms despite this first line treatment. The objective of our paper is to review relevant studies for the pharmacologic management of anxiety disorders resistant to the first line treatment. For this purpose, we conducted a pubmed/medline search for double-blind placebo-controlled trials of treatment-resistant anxiety disorders. An adequate trial for a SRI in the treatment of obsessive-compulsive disorder (OCD) should continue for at least 12 weeks. Special considerations of the comorbidities and symptom profile could help in the choice of an appropriate pharmacotherapy. Several trials have highlighted the efficacy of antipsychotics as an add-on to SRI in treatment-resistant OCD such as haloperidol more so when comorbid with a tic disorder, or risperidone that can reduce OCD as well as depressive symptoms. Aripiprazole has been shown efficacious in two placebo-controlled double-blind trials, while the efficacy of quetiapine and olanzapine remains controversial. Other trials showed some efficacy of anticonvulsants (lamotrigine, topiramate), pindolol, memantin and N-acetylcystein as an adjunctive treatment to SRI for resistant OCD. Few trials have investigated selective serotonin reuptake inhibitors (SSRI) or SNRI resistant generalized anxiety disorder showing a failure of adjunctive therapy with olanzapine, quetiapine, ziprasidone and risperidone. These studies were underpowered and very limited in number. Adjunctive risperidone for resistant post-traumatic stress disorder (PTSD) showed benefit in some but not all trials. Olanzapine was beneficial for the reduction of the CAPS score in addition to the improvement of sleep disturbances. Furthermore, prazosin was efficacious by reducing PTSD symptoms, sleep disturbances, nightmares, and psychological distress. One double-blind placebo-controlled study was conducted to investigate treatment-resistant social phobia showing no benefit of pindolol add-on paroxetine. Our results demonstrate that the pharmacological management of treatment-resistant anxiety disorders is not sufficiently investigated in double-blind placebo-controlled trials, despite a growing evidence in favor of antipsychotics and some other pharmacological agents in resistant OCD and, to a lesser extent, PTSD. Hence, there is a crucial need for larger double-blind placebo-controlled trials for resistant anxiety disorders. Finally, being out of the scope of our review, we omitted studies of non-pharmacologic therapies. Copyright © 2014. Published by Elsevier Masson SAS.

Patient-oriented randomisation: A new trial design applied in the Neuroleptic Strategy Study.

PubMed

Schulz, Constanze; Timm, Jürgen; Cordes, Joachim; Gründer, Gerhard; Mühlbauer, Bernd; Rüther, Eckart; Heinze, Martin

2016-06-01

The 'gold standard' for clinical studies is a randomised controlled trial usually comparing specific treatments. If the scientific study expands to strategy comparison with each strategy including various treatments, the research problems are increasingly complicated. The strategy debate in the psychiatric community is the starting point for the development of our new design. It is widely accepted that second-generation antipsychotics are the therapy of choice in the treatment of schizophrenia. However, their general superiority over first-generation antipsychotics could not be demonstrated in recent randomised controlled trials. Furthermore, we are becoming increasingly aware that the experimental conditions of randomised controlled trials, as in the European First Episode Schizophrenia Trial and Clinical Antipsychotic Trials of Intervention Effectiveness Phase 1 studies, may be inappropriate for psychiatric treatments. The high heterogeneity in the patient population produces discrepancies between daily clinical perception and randomised controlled trials results. The patient-oriented approach in the Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study reflects everyday clinical practice. The results, however, are highly dependent on the physicians' preferences. The goal of the design described here is to take an intermediate path between randomised controlled trials and clinical studies such as Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study, combining the advantages of both study types. The idea is to randomise two treatment pairs each consisting of one first-generation antipsychotic and one second-generation antipsychotic in a first step and subsequently, to involve the investigators in deciding for a pair most appropriate to the patients' needs and then to randomise the allocation to one drug (first-generation antipsychotic or second-generation antipsychotic) of that chosen pair. This idea was first implemented in the clinical trial, the Neuroleptic Strategy Study, with a randomised design comparing efficacy and safety of two different strategies: either to use first-generation antipsychotics (haloperidol and flupentixol) or second-generation antipsychotics (olanzapine, aripiprazole and quetiapine) in patients suffering from schizophrenia. In the course of the Neuroleptic Strategy Study, feasibility of this design was demonstrated. All aspects of the new design were implemented: randomisation process, documentation of responses from investigators as well as patients and drug logistic experience. In implementing the design, furthermore, we could investigate its theoretical properties. The physicians' preferences for specific drugs used for the respective patients were analysed. The idea of patient-oriented randomisation can be generalised. In light of the heterogeneity and complexity of patient-drug interaction, this design should prove particularly useful. © The Author(s) 2016.

Importance of placebo effect in cough clinical trials.

PubMed

Eccles, Ron

2010-01-01

Cough is a unique symptom because, unlike sneeze and other symptoms, it can be under voluntary control and this complicates clinical trials on cough medicines. All over-the-counter cough medicines (OTC) are very effective treatments because of their placebo effect. The placebo effect is enhanced by expectancy related to advertising, brand, packaging, and formulation. This placebo effect creates a problem for the conduct of clinical trials on OTC cough medicines that attempt to demonstrate the efficacy of a pharmacological agent above that of any placebo effect. Up to 85% of the efficacy of some cough medicines can be attributed to a placebo effect. The placebo effect apparent in clinical trials consists of several components: natural recovery, regression of cough response toward mean, demulcent effect, effect of sweetness, voluntary control, and effects related to expectancy and meaning of the treatment. The placebo effect has been studied most in the pain model, and placebo analgesia is reported to depend on the activation of endogenous opioid systems in the brain; this model may be applicable to cough. A balanced placebo design may help to control for the placebo effect, but this trial design may not be acceptable due to deception of patients. The placebo effect in clinical trials may be controlled by use of a crossover design, where feasible, and the changes in the magnitude of the placebo effect in this study design are discussed.

Systematic review of randomised controlled trials of the effects of caffeine or caffeinated drinks on blood glucose concentrations and insulin sensitivity in people with diabetes mellitus.

PubMed

Whitehead, N; White, H

2013-04-01

Compounds other than macronutrients have been shown to influence blood glucose concentrations and insulin sensitivity in people with diabetes, with caffeine being one such substance. The present study systematically reviewed the evidence of the effects of caffeine on blood glucose concentrations and/or insulin sensitivity in people with diabetes. Four databases, including MEDLINE and EMBASE, were searched up to 1 February 2012. Randomised controlled trials (RCTs) investigating the effects of caffeine on blood glucose and/or insulin sensitivity in humans, diagnosed with type I, type II or gestational diabetes mellitus (GDM), were included. Quality assessment and data extraction were conducted and agreed by both authors. Of 253 articles retrieved, nine trials (134 participants) were identified. Trials in people with type II diabetes demonstrated that the ingestion of caffeine (approximately 200-500 mg) significantly increased blood glucose concentrations by 16-28% of the area under the curve (AUC) and insulin concentrations by 19-48% of the AUC when taken prior to a glucose load, at the same time as decreasing insulin sensitivity by 14-37%. In type I diabetes, trials indicated enhanced recognition and a reduced duration of hypoglycaemic episodes following ingestion of 400-500 mg caffeine, without altering glycated haemoglobin. In GDM, a single trial demonstrated that approximately 200 mg of caffeine induced a decrease in insulin sensitivity by 18% and a subsequent increase in blood glucose concentrations by 19% of the AUC. Evidence indicates a negative effect of caffeine intake on blood glucose control in individuals with type II diabetes, as replicated in a single trial in GDM. Larger-scale RCTs of longer duration are needed to determine the effects of timing and dose. Early indications of a reduced duration and an improved awareness of hypoglycaemia in type I diabetes require further confirmation. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

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.

An analysis of the effect of funding source in randomized clinical trials of second generation antipsychotics for the treatment of schizophrenia.

PubMed

Montgomery, John H; Byerly, Matthew; Carmody, Thomas; Li, Baitao; Miller, Daniel R; Varghese, Femina; Holland, Rhiannon

2004-12-01

The effect of funding source on the outcome of randomized controlled trials has been investigated in several medical disciplines; however, psychiatry has been largely excluded from such analyses. In this article, randomized controlled trials of second generation antipsychotics in schizophrenia are reviewed and analyzed with respect to funding source (industry vs. non-industry funding). A literature search was conducted for randomized, double-blind trials in which at least one of the tested treatments was a second generation antipsychotic. In each study, design quality and study outcome were assessed quantitatively according to rating scales. Mean quality and outcome scores were compared in the industry-funded studies and non-industry-funded studies. An analysis of the primary author's affiliation with industry was similarly performed. Results of industry-funded studies significantly favored second generation over first generation antipsychotics when compared to non-industry-funded studies. Non-industry-funded studies showed a trend toward higher quality than industry-funded studies; however, the difference between the two was not significant. Also, within the industry-funded studies, outcomes of trials involving first authors employed by industry sponsors demonstrated a trend toward second generation over first generation antipsychotics to a greater degree than did trials involving first authors employed outside the industry (p=0.05). While the retrospective design of the study limits the strength of the findings, the data suggest that industry bias may occur in randomized controlled trials in schizophrenia. There appears to be several sources by which bias may enter clinical research, including trial design, control of data analysis and multiplicity/redundancy of trials.

Development of an attention-touch control for manual cervical distraction: a pilot randomized clinical trial for patients with neck pain.

PubMed

Gudavalli, M Ram; Salsbury, Stacie A; Vining, Robert D; Long, Cynthia R; Corber, Lance; Patwardhan, Avinash G; Goertz, Christine M

2015-06-05

Manual cervical distraction (MCD) is a traction-based therapy performed with a manual contact over the cervical region producing repeating cycles while patients lie prone. This study evaluated a traction force-based minimal intervention for use as an attention-touch control in clinical trials of MCD for patients with chronic neck pain. We conducted a mixed-methods, pilot randomized clinical trial in adults with chronic neck pain. Participants were allocated to three traction force ranges of MCD: low force/minimal intervention (0-20 N), medium force (21-50 N), or high force (51-100 N). Clinicians delivered five treatments over two weeks consisting of three sets of five cycles of MCD at the C5 vertebra and occiput. Traction forces were measured at each treatment. Patient-reported outcomes included a pain visual analogue scale (VAS), Neck Disability Index (NDI), Credibility and Expectancy Questionnaire (CEQ), and adverse effects. A qualitative interview evaluated treatment group allocation perceptions. We randomized 48 participants, allocating an average of five each month. Forty-five participants completed the trial with three participants lost to follow-up. Most participants were women (65%) and white (92%) with a mean (SD) age of 46.8 (12.5) years. Mean traction force values were within the prescribed force ranges for each group at the C5 and occiput levels. Neck pain VAS demonstrated a benefit for high traction force MCD compared to the low force group [adjusted mean difference 15.6; 95% confidence interval (CI) 1.6 to 29.7]. Participants in the medium traction force group demonstrated improvements in NDI compared to the low force group (adjusted mean difference 3.0; 95% CI 0.1 to 5.9), as did participants in the high traction force group (adjusted mean difference 2.7; 95% CI -0.1 to 5.6). CEQ favored the high force group. Most low force participants correctly identified their treatment allocation in the qualitative interview. No serious adverse events were documented. This pilot study demonstrated the feasibility of a clinical trial protocol and the utility of a traction-based, minimal intervention as an attention-touch control for future efficacy trials of MCD for patients with neck pain. ClinicalTrials.gov NCT01765751 (Registration Date 30 May 2012).

Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: randomised controlled feasibility trial

PubMed Central

Neal, Richard D; Barham, Allan; Bongard, Emily; Edwards, Rhiannon Tudor; Fitzgibbon, Jim; Griffiths, Gareth; Hamilton, Willie; Hood, Kerenza; Nelson, Annmarie; Parker, David; Porter, Cath; Prout, Hayley; Roberts, Kirsty; Rogers, Trevor; Thomas-Jones, Emma; Tod, Angela; Yeo, Seow Tien; Hurt, Chris N

2017-01-01

Background: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. Methods: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. Results: The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. Conclusions: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care. PMID:28072761

Task difficulty modulates brain-behavior correlations in language production and cognitive control: Behavioral and fMRI evidence from a phonological go/no-go picture-naming paradigm.

PubMed

Zhang, Haoyun; Eppes, Anna; Beatty-Martínez, Anne; Navarro-Torres, Christian; Diaz, Michele T

2018-06-19

Language production and cognitive control are complex processes that involve distinct yet interacting brain networks. However, the extent to which these processes interact and their neural bases have not been thoroughly examined. Here, we investigated the neural and behavioral bases of language production and cognitive control via a phonological go/no-go picture-naming task. Naming difficulty and cognitive control demands (i.e., conflict monitoring and response inhibition) were manipulated by varying the proportion of naming trials (go trials) and inhibition trials (no-go trials) across task runs. The results demonstrated that as task demands increased, participants' behavioral performance declined (i.e., longer reaction times on naming trials, more commission errors on inhibition trials) whereas brain activation generally increased. Increased activation was found not only within the language network but also in domain-general control regions. Additionally, right superior and inferior frontal and left supramarginal gyri were sensitive to increased task difficulty during both language production and response inhibition. We also found both positive and negative brain-behavior correlations. Most notably, increased activation in sensorimotor regions, such as precentral and postcentral gyri, was associated with better behavioral performance, in both successful picture naming and successful inhibition. Moreover, comparing the strength of correlations across conditions indicated that the brain-behavior correlations in sensorimotor regions that were associated with improved performance became stronger as task demands increased. Overall, our results suggest that cognitive control demands affect language production, and that successfully coping with increases in task difficulty relies on both language-specific and domain-general cognitive control regions.

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

PubMed

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

2014-03-01

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

The applications of regenerative medicine in sinus lift procedures: A systematic review.

PubMed

Correia, Francisco; Pozza, Daniel Humberto; Gouveia, Sónia; Felino, António; Faria E Almeida, Ricardo

2018-04-01

Findings in regenerative medicine applied to the sinus lift procedures. Evaluate the effectiveness of regenerative medicine in sinus lift. An extensive search for manuscripts were performed by using different combinations of keywords and MeSH terms (Pub-med; Embase; Scopus; Web of Science Core Collection; Medline; Current Contents Connect; Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full text selected articles are written in English, Portuguese, Spanish, Italian, German, or French, and published until 28 of November 2016. Inclusion criteria were: implant osteointegration, radiographic, histologic, and/or histomorphometric analysis, clinical studies in humans using of regenerative medicine. This systematic review was performed by selecting only randomized controlled clinical trials and controlled clinical trials. Eighteen published studies (11 CT and 7 RCT) were considered eligible for inclusion in the present systematic review. These studies demonstrated considerable variation of biomaterial and cell technics used, study design, sinus lift technic, outcomes, follow-up, and results. Only few studies have demonstrated potential of regenerative medicine in sinus lift; further randomized clinical trials are needed to achieve more accurate results. © 2017 Wiley Periodicals, Inc.

The inherent paradox of clinical trials in psychiatry.

PubMed Central

Helmchen, H; Müller-Oerlinghausen, B

1975-01-01

The authors sum up the central issue of ethics in the conduct of controlled clinical trials in these two paradoxes: 'first, it is unethical to use treatment the efficacy of which has not been examined scientifically; second, it is also unethical to examine the efficacy of treatment scientifically.' In this paper they set out to demonstrate how these antithetical statements apply in controlled trials conducted in psychiatric patients. In such trials the problem of obtaining informed consent may be acute, but in these patients giving 'informed' consent might contribute to a further exacerbation of the illness. Nevertheless the problem cannot be evaded, and scientific judgments must be applied to treatment for it to be sound and improved for the further benefit of patients. These problems in the case of psychiatric controlled trials are a part of the methodology, and in Germany a new drug law has been drafted to attempt to clarify the issue. The authors briefly discuss its application, and its consequences if such a law were enacted. British psychiatrists have exactly the same problems to face but so far no attempts have been made to establish a legal framework. PMID:775089

Therapist adherence in the strong without anorexia nervosa (SWAN) study: A randomized controlled trial of three treatments for adults with anorexia nervosa.

PubMed

Andony, Louise J; Tay, Elaine; Allen, Karina L; Wade, Tracey D; Hay, Phillipa; Touyz, Stephen; McIntosh, Virginia V W; Treasure, Janet; Schmidt, Ulrike H; Fairburn, Christopher G; Erceg-Hurn, David M; Fursland, Anthea; Crosby, Ross D; Byrne, Susan M

2015-12-01

To develop a psychotherapy rating scale to measure therapist adherence in the Strong Without Anorexia Nervosa (SWAN) study, a multi-center randomized controlled trial comparing three different psychological treatments for adults with anorexia nervosa. The three treatments under investigation were Enhanced Cognitive Behavioural Therapy (CBT-E), the Maudsley Anorexia Nervosa Treatment for Adults (MANTRA), and Specialist Supportive Clinical Management (SSCM). The SWAN Psychotherapy Rating Scale (SWAN-PRS) was developed, after consultation with the developers of the treatments, and refined. Using the SWAN-PRS, two independent raters initially rated 48 audiotapes of treatment sessions to yield inter-rater reliability data. One rater proceeded to rate a total of 98 audiotapes from 64 trial participants. The SWAN-PRS demonstrated sound psychometric properties, and was considered a reliable measure of therapist adherence. The three treatments were highly distinguishable by independent raters, with therapists demonstrating significantly more behaviors consistent with the actual allocated treatment compared to the other two treatment modalities. There were no significant site differences in therapist adherence observed. The findings provide support for the internal validity of the SWAN study. The SWAN-PRS was deemed suitable for use in other trials involving CBT-E, MANTRA, or SSCM. The Authors. International Journal of Eating Disorders Published by Wiley Periodicals, Inc.

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

PubMed

Sawada, Hideyuki

2017-05-01

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

Meditation awareness training for the treatment of workaholism: A controlled trial.

PubMed

Van Gordon, William; Shonin, Edo; Dunn, Thomas J; Garcia-Campayo, Javier; Demarzo, Marcelo M P; Griffiths, Mark D

2017-06-01

Background and aims Workaholism is a form of behavioral addiction that can lead to reduced life and job satisfaction, anxiety, depression, burnout, work-family conflict, and impaired productivity. Given the number of people affected, there is a need for more targeted workaholism treatments. Findings from previous case studies successfully utilizing second-generation mindfulness-based interventions (SG-MBIs) for treating behavioral addiction suggest that SG-MBIs may be suitable for treating workaholism. This study conducted a controlled trial to investigate the effects of an SG-MBI known as meditation awareness training (MAT) on workaholism. Methods Male and female adults suffering from workaholism (n = 73) were allocated to MAT or a waiting-list control group. Assessments were performed at pre-, post-, and 3-month follow-up phases. Results MAT participants demonstrated significant and sustained improvements over control-group participants in workaholism symptomatology, job satisfaction, work engagement, work duration, and psychological distress. Furthermore, compared to the control group, MAT participants demonstrated a significant reduction in hours spent working but without a decline in job performance. Discussion and conclusions MAT may be a suitable intervention for treating workaholism. Further controlled intervention studies investigating the effects of SG-MBIs on workaholism are warranted.

Meditation awareness training for the treatment of workaholism: A controlled trial

PubMed Central

Van Gordon, William; Shonin, Edo; Dunn, Thomas J.; Garcia-Campayo, Javier; Demarzo, Marcelo M. P.; Griffiths, Mark D.

2017-01-01

Background and aims Workaholism is a form of behavioral addiction that can lead to reduced life and job satisfaction, anxiety, depression, burnout, work–family conflict, and impaired productivity. Given the number of people affected, there is a need for more targeted workaholism treatments. Findings from previous case studies successfully utilizing second-generation mindfulness-based interventions (SG-MBIs) for treating behavioral addiction suggest that SG-MBIs may be suitable for treating workaholism. This study conducted a controlled trial to investigate the effects of an SG-MBI known as meditation awareness training (MAT) on workaholism. Methods Male and female adults suffering from workaholism (n = 73) were allocated to MAT or a waiting-list control group. Assessments were performed at pre-, post-, and 3-month follow-up phases. Results MAT participants demonstrated significant and sustained improvements over control-group participants in workaholism symptomatology, job satisfaction, work engagement, work duration, and psychological distress. Furthermore, compared to the control group, MAT participants demonstrated a significant reduction in hours spent working but without a decline in job performance. Discussion and conclusions MAT may be a suitable intervention for treating workaholism. Further controlled intervention studies investigating the effects of SG-MBIs on workaholism are warranted. PMID:28425778

Cognitive Training and Transcranial Direct Current Stimulation for Mild Cognitive Impairment in Parkinson's Disease: A Randomized Controlled Trial

PubMed Central

Gasson, Natalie; Johnson, Andrew R.; Booth, Leon; Loftus, Andrea M.

2018-01-01

This study examined whether standard cognitive training, tailored cognitive training, transcranial direct current stimulation (tDCS), standard cognitive training + tDCS, or tailored cognitive training + tDCS improved cognitive function and functional outcomes in participants with PD and mild cognitive impairment (PD-MCI). Forty-two participants with PD-MCI were randomized to one of six groups: (1) standard cognitive training, (2) tailored cognitive training, (3) tDCS, (4) standard cognitive training + tDCS, (5) tailored cognitive training + tDCS, or (6) a control group. Interventions lasted 4 weeks, with cognitive and functional outcomes measured at baseline, post-intervention, and follow-up. The trial was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12614001039673). While controlling for moderator variables, Generalized Linear Mixed Models (GLMMs) showed that when compared to the control group, the intervention groups demonstrated variable statistically significant improvements across executive function, attention/working memory, memory, language, activities of daily living (ADL), and quality of life (QOL; Hedge's g range = 0.01 to 1.75). More outcomes improved for the groups that received standard or tailored cognitive training combined with tDCS. Participants with PD-MCI receiving cognitive training (standard or tailored) or tDCS demonstrated significant improvements on cognitive and functional outcomes, and combining these interventions provided greater therapeutic effects. PMID:29780572

Self-management education for rehabilitation inpatients suffering from inflammatory bowel disease: a cluster-randomized controlled trial.

PubMed

Reusch, A; Weiland, R; Gerlich, C; Dreger, K; Derra, C; Mainos, D; Tuschhoff, T; Berding, A; Witte, C; Kaltz, B; Faller, H

2016-12-01

Although inflammatory bowel disease (IBD) affects patients' psychological well-being, previous educational programs have failed to demonstrate effects on psychosocial outcomes and quality of life. Therefore, we developed a group-based psychoeducational program that combined provision of both medical information and psychological self-management skills, delivered in an interactive manner, and evaluated it in a large, cluster-randomized trial. We assigned 540 rehabilitation inpatients suffering from IBD (mean age 43 years, 66% female) to either the new intervention or a control group comprising the same overall intensity and the same medical information, but only general psychosocial information. The primary outcome was patient-reported IBD-related concerns. Secondary outcomes included disease knowledge, coping, self-management skills, fear of progression, anxiety, depression and quality of life. Assessments took place at baseline, end of rehabilitation and after 3 and 12 months.The psychoeducational self-management program did not prove superior to the control group regarding primary and secondary outcomes. However, positive changes over time occurred in both groups regarding most outcomes. The superior effectiveness of the newly developed psychoeducational program could not be demonstrated. Since the intervention and control groups may have been too similar, this trial may have been too conservative to produce between-group effects. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Memory-guided selective attention: Single experiences with conflict have long-lasting effects on cognitive control.

PubMed

Brosowsky, Nicholaus P; Crump, Matthew J C

2018-05-17

Adjustments in cognitive control, as measured by congruency sequence effects, are thought to be influenced by both external stimuli and internal goals. However, this dichotomy has often overshadowed the potential contribution of past experience stored in memory. Here, we examine the role of long-term episodic memory in guiding selective attention. Our aim was to demonstrate new evidence that selective attention can be modulated by long-term retrieval of stimulus-specific attentional control settings. All the experiments used a modified flanker task involving multiple unique stimuli. Critically, each stimulus was only presented twice during the experiment: first as a prime, and second as a probe. Experiments 1 and 2 varied the number of intervening trials between prime and probe and manipulated the amount of conflict using a secondary task. Experiment 3 ensured that specific colors assigned to prime stimuli were not repeated when presented as probes. Across both Experiments 1 and 2, we consistently found smaller congruency effects on probe trials when its associated prime trial was incongruent compared with congruent, demonstrating long-term congruency sequence effects. However, Experiment 3 showed no evidence for long-term effects. These findings suggest long-term preservation of selective attention processing at the episodic level, and implicate a role for memory in updating cognitive control. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A Method for Precision Closed-Loop Irrigation Using a Modified PID Control Algorithm

NASA Astrophysics Data System (ADS)

Goodchild, Martin; Kühn, Karl; Jenkins, Malcolm; Burek, Kazimierz; Dutton, Andrew

2016-04-01

The benefits of closed-loop irrigation control have been demonstrated in grower trials which show the potential for improved crop yields and resource usage. Managing water use by controlling irrigation in response to soil moisture changes to meet crop water demands is a popular approach but requires knowledge of closed-loop control practice. In theory, to obtain precise closed-loop control of a system it is necessary to characterise every component in the control loop to derive the appropriate controller parameters, i.e. proportional, integral & derivative (PID) parameters in a classic PID controller. In practice this is often difficult to achieve. Empirical methods are employed to estimate the PID parameters by observing how the system performs under open-loop conditions. In this paper we present a modified PID controller, with a constrained integral function, that delivers excellent regulation of soil moisture by supplying the appropriate amount of water to meet the needs of the plant during the diurnal cycle. Furthermore, the modified PID controller responds quickly to changes in environmental conditions, including rainfall events which can result in: controller windup, under-watering and plant stress conditions. The experimental work successfully demonstrates the functionality of a constrained integral PID controller that delivers robust and precise irrigation control. Coir substrate strawberry growing trial data is also presented illustrating soil moisture control and the ability to match water deliver to solar radiation.

Verbal implicit sequence learning in persons who stutter and persons with Parkinson's disease.

PubMed

Smits-Bandstra, Sarah; Gracco, Vincent

2013-01-01

The authors investigated the integrity of implicit learning systems in 14 persons with Parkinson's disease (PPD), 14 persons who stutter (PWS), and 14 control participants. In a 120-min session participants completed a verbal serial reaction time task, naming aloud 4 syllables in response to 4 visual stimuli. Unbeknownst to participants, the syllables formed a repeating 8-item sequence. PWS and PPD demonstrated slower reaction times for early but not late learning trials relative to controls reflecting delays but not deficiencies in general learning. PPD also demonstrated less accuracy in general learning relative to controls. All groups demonstrated similar limited explicit sequence knowledge. Both PWS and PPD demonstrated significantly less implicit sequence learning relative to controls, suggesting that stuttering may be associated with compromised functional integrity of the cortico-striato-thalamo-cortical loop.

Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy

PubMed Central

Bartus, Raymond T; Weinberg, Marc S; Samulski, R. Jude

2014-01-01

Over the past decade, nine gene therapy clinical trials for Parkinson's disease (PD) have been initiated and completed. Starting with considerable optimism at the initiation of each trial, none of the programs has yet borne sufficiently robust clinical efficacy or found a clear path toward regulatory approval. Despite the immediately disappointing nature of the efficacy outcomes in these trials, the clinical data garnered from the individual studies nonetheless represent tangible and significant progress for the gene therapy field. Collectively, the clinical trials demonstrate that we have overcome the major safety hurdles previously suppressing central nervous system (CNS) gene therapy, for none produced any evidence of untoward risk or harm after administration of various vector-delivery systems. More importantly, these studies also demonstrated controlled, highly persistent generation of biologically active proteins targeted to structures deep in the human brain. Therefore, a renewed, focused emphasis must be placed on advancing clinical efficacy by improving clinical trial design, patient selection and outcome measures, developing more predictive animal models to support clinical testing, carefully performing retrospective analyses, and most importantly moving forward—beyond our past limits. PMID:24356252

Multi-center, randomized, placebo-controlled trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease: a study protocol for the INOX trial.

PubMed

Lacasse, Yves; Bernard, Sarah; Sériès, Frédéric; Nguyen, Van Hung; Bourbeau, Jean; Aaron, Shawn; Maltais, François

2017-01-09

Long-term oxygen therapy (LTOT) is the only component of the management of chronic obstructive pulmonary disease (COPD) that improves survival in patients with severe daytime hypoxemia. LTOT is usually provided by a stationary oxygen concentrator and is recommended to be used for at least 15-18 h a day. Several studies have demonstrated a deterioration in arterial blood gas pressures and oxygen saturation during sleep in patients with COPD, even in those not qualifying for LTOT. The suggestion has been made that the natural progression of COPD to its end stages of chronic pulmonary hypertension, severe hypoxemia, right heart failure, and death is dependent upon the severity of desaturation occurring during sleep. The primary objective of the International Nocturnal Oxygen (INOX) trial is to determine, in patients with COPD not qualifying for LTOT but who present significant nocturnal arterial oxygen desaturation, whether nocturnal oxygen provided for a period of 3 years decreases mortality or delay the prescription of LTOT. The INOX trial is a 3-year, multi-center, placebo-controlled, randomized trial of nocturnal oxygen therapy added to usual care. Eligible patients are those with a diagnosis of COPD supported by a history of past smoking and obstructive disease who fulfill our definition of significant nocturnal oxygen desaturation (i.e., ≥ 30% of the recording time with transcutaneous arterial oxygen saturation < 90% on either of two consecutive recordings). Patients allocated in the control group receive room air delivered by a concentrator modified to deliver 21% oxygen. The comparison is double blind. The primary outcome is a composite of mortality from all cause or requirement for LTOT. Secondary outcomes include quality of life and utility measures, costs from a societal perspective and compliance with oxygen therapy. The follow-up period is intended to last at least 3 years. The benefits of LTOT have been demonstrated whereas those of nocturnal oxygen therapy alone have not. The INOX trial will likely determine whether supplemental oxygen during sleep is effective in reducing mortality, delaying the need for LTOT and improving health-related quality of life in patients with COPD who desaturate overnight. Current Controlled Trials ISRCTN50085100 ; ClinicalTrials.gov NCT01044628 (date of registration: January 6, 2010).

A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome.

PubMed

Leigh, Mary Jacena S; Nguyen, Danh V; Mu, Yi; Winarni, Tri I; Schneider, Andrea; Chechi, Tasleem; Polussa, Jonathan; Doucet, Paul; Tassone, Flora; Rivera, Susan M; Hessl, David; Hagerman, Randi J

2013-04-01

Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Previous open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, aged 3.5 years to 16 years (n = 55, mean age 9.2 [SD, 3.6] years). Participants were randomized to minocycline or placebo for 3 months and then switched to the other treatment. Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared with placebo (2.49 ± 0.13 and 2.97 ± 0.13, respectively, p = .0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analog Scale (minocycline: 5.26 cm ± 0.46 cm, placebo: 4.05 cm ± 0.46 cm; p = .0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding, and preliminary efficacy analysis results known to investigators. Minocycline treatment for 3 months in children with FXS resulted in greater global improvement than placebo. Treatment for 3 months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline.

A Randomized Double-Blind, Placebo-Controlled Trial of Minocycline in Children and Adolescents with Fragile X Syndrome

PubMed Central

Leigh, Mary Jacena S.; Nguyen, Danh V.; Mu, Yi; Winarni, Tri I.; Schneider, Andrea; Chechi, Tasleem; Polussa, Jonathan; Doucet, Paul; Tassone, Flora; Rivera, Susan M.; Hessl, David; Hagerman, Randi J.

2013-01-01

Objective Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Prior open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial. Method Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, ages 3.5-16 years (n=55, mean age 9.2 (SD 3.6 years)). Participants were randomized to minocycline or placebo for three months, then switched to the other treatment. Results Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared to placebo (2.49 ±0.13, 2.97 ±0.13, respectively, p 0.0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analoge Scale (minocycline 5.26 cm ±0.46 cm, placebo 4.05 cm±0.46cm; p 0.0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding and preliminary efficacy analysis results known to investigators. Conclusion Minocycline treatment for three months in children with FXS resulted in greater global improvement than placebo. Treatment for three months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline. PMID:23572165

Effects of a Patient-Provider, Collaborative, Medication-Planning Tool: A Randomized, Controlled Trial

PubMed Central

Wolf, Michael S.; Kaiser, Darren; Morrow, Daniel G.

2016-01-01

Among patients with various levels of health literacy, the effects of collaborative, patient-provider, medication-planning tools on outcomes relevant to self-management are uncertain. Objective. Among adult patients with type II diabetes mellitus, we tested the effectiveness of a medication-planning tool (Medtable™) implemented via an electronic medical record to improve patients' medication knowledge, adherence, and glycemic control compared to usual care. Design. A multicenter, randomized controlled trial in outpatient primary care clinics. 674 patients received either the Medtable tool or usual care and were followed up for up to 12 months. Results. Patients who received Medtable had greater knowledge about indications for medications in their regimens and were more satisfied with the information about their medications. Patients' knowledge of drug indication improved with Medtable regardless of their literacy status. However, Medtable did not improve patients' demonstrated medication use, regimen adherence, or glycemic control (HbA1c). Conclusion. The Medtable tool supported provider/patient collaboration related to medication use, as reflected in patient satisfaction with communication, but had limited impact on patient medication knowledge, adherence, and HbA1c outcomes. This trial is registered with ClinicalTrials.gov NCT01296633. PMID:27699179

Older Adults can Learn to Learn New Motor Skills

PubMed Central

Seidler, Rachael D.

2007-01-01

Many studies have demonstrated that aging is associated with declines in skill acquisition. In the current study, we tested whether older adults could acquire general, transferable knowledge about skill learning processes. Older adult participants learned five different motor tasks. Two older adult control groups performed the same number of trials, but learned only one task. The experimental group exhibited faster learning than that seen in the control groups. These data demonstrate that older adults can learn to learn new motor skills. PMID:17602760

Task-Oriented Training with Computer Games for People with Rheumatoid Arthritis or Hand Osteoarthritis: A Feasibility Randomized Controlled Trial.

PubMed

Srikesavan, Cynthia Swarnalatha; Shay, Barbara; Szturm, Tony

2016-09-13

To examine the feasibility of a clinical trial on a novel, home-based task-oriented training with conventional hand exercises in people with rheumatoid arthritis or hand osteoarthritis. To explore the experiences of participants who completed their respective home exercise programmes. Thirty volunteer participants aged between 30 and 60 years and diagnosed with rheumatoid arthritis or hand osteoarthritis were proposed for a single-center, assessor-blinded, randomized controlled trial ( ClinicalTrials.gov : NCT01635582). Participants received task-oriented training with interactive computer games and objects of daily life or finger mobility and strengthening exercises. Both programmes were home based and were done four sessions per week with 20 minutes each session for 6 weeks. Major feasibility outcomes were number of volunteers screened, randomized, and retained; completion of blinded assessments, exercise training, and home exercise sessions; equipment and data management; and clinical outcomes of hand function. Reaching the recruitment target in 18 months and achieving exercise compliance >80% were set as success criteria. Concurrent with the trial, focus group interviews explored experiences of those participants who completed their respective programmes. After trial initiation, revisions in inclusion criteria were required to promote recruitment. A total of 17 participants were randomized and 15 were retained. Completion of assessments, exercise training, and home exercise sessions; equipment and data collection and management demonstrated excellent feasibility. Both groups improved in hand function outcomes and exercise compliance was above 85%. Participants perceived both programmes as appropriate and acceptable. Participants who completed task-oriented training also agreed that playing different computer games was enjoyable, engaging, and motivating. Findings demonstrate initial evidence on recruitment, feasibility of trial procedures, and acceptability of task-oriented training in people with rheumatoid arthritis or hand osteoarthritis. Since the pilot trial was unsuccessful in participant recruitment, a large trial will not follow.

Using essential oils to control moss and liverwort in containers

Treesearch

Nabil Khadduri

2011-01-01

Liverwort and moss are economically significant weeds across a range of US container production sites, including forest seedling greenhouse culture in the Pacific Northwest. We have demonstrated the effectiveness of essential oils, or distilled plant extracts, in controlling liverwort and moss container weeds over three seasons of trials. When applied at the...

Behavior Therapy for Pediatric Trichotillomania: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Franklin, Martin E.; Edson, Aubrey L.; Ledley, Deborah A.; Cahill, Shawn P.

2011-01-01

Objective: To examine the efficacy and durability of a behavioral therapy (BT) protocol for pediatric TTM compared with a minimal attention control (MAC) condition. It was hypothesized that the BT condition would be superior to MAC at the end of acute treatment, and would also demonstrate durability of gains through the maintenance treatment…

The Girlfriends Project: Evaluating a Promising Community-Based Intervention from a Bottom-Up Perspective

ERIC Educational Resources Information Center

Hawk, Mary

2015-01-01

Randomized controlled trials are the gold standard in research but may not fully explain or predict outcome variations in community-based interventions. Demonstrating efficacy of externally driven programs in well-controlled environments may not translate to community-based implementation where resources and priorities vary. A bottom-up evaluation…

The use of cell phone support for non-adherent HIV-infected youth and young adults: an initial randomized and controlled intervention trial.

PubMed

Belzer, Marvin E; Naar-King, Sylvie; Olson, Johanna; Sarr, Moussa; Thornton, Sarah; Kahana, Shoshana Y; Gaur, Aditya H; Clark, Leslie F

2014-04-01

This randomized behavioral trial examined whether youth living with HIV (YLH) receiving cell-phone support with study funded phone plans, demonstrated improved adherence and viral control during the 24 week intervention and 24 weeks post-intervention compared to controls. Monday through Friday phone calls confirmed medications were taken, provided problem-solving support, and referred to services to address adherence barriers. Of 37 participants (ages 15-24), 62 % were male and 70 % were African American. Self-reported adherence was significantly higher in the intervention group compared to the control at 24 and 48 weeks for the past month (P = 0.007) and log 10 HIV VL was significantly lower at both 24 weeks (2.82 versus 4.52 P = 0.002) and 48 weeks (3.23 versus 4.23 P = 0.043). Adherence and viral load showed medium to large effect sizes across the 48 week study. This is the first study to demonstrate sustained clinically significant reductions in HIV VL using youth friendly technology.

The Use of Cell Phone Support for Non-adherent HIV-Infected Youth and Young Adults: An Initial Randomized and Controlled Intervention Trial

PubMed Central

Belzer, Marvin E.; Naar-King, Sylvie; Olson, Johanna; Sarr, Moussa; Thornton, Sarah; Kahana, Shoshana Y.; Gaur, Aditya H.; Clark, Leslie F.

2014-01-01

This randomized behavioral trial examined whether youth living with HIV (YLH) receiving cell-phone support with study funded phone plans, demonstrated improved adherence and viral control during the 24 week intervention and 24 weeks post-intervention compared to controls. Monday through Friday phone calls confirmed medications were taken, provided problem-solving support, and referred to services to address adherence barriers. Of 37 participants (ages 15–24), 62 % were male and 70 % were African American. Self-reported adherence was significantly higher in the intervention group compared to the control at 24 and 48 weeks for the past month (P = 0.007) and log 10 HIV VL was significantly lower at both 24 weeks (2.82 versus 4.52 P = 0.002) and 48 weeks (3.23 versus 4.23 P = 0.043). Adherence and viral load showed medium to large effect sizes across the 48 week study. This is the first study to demonstrate sustained clinically significant reductions in HIV VL using youth friendly technology. PMID:24271347

Efficacy and safety of Indigo naturalis extract in oil (Lindioil) in treating nail psoriasis: a randomized, observer-blind, vehicle-controlled trial.

PubMed

Lin, Yin-Ku; See, Lai-Chu; Huang, Yu-Huei; Chang, Ya-Ching; Tsou, Teng-Cheng; Lin, Tung-Yi; Lin, Na-Ling

2014-06-15

Treating nail psoriasis is notoriously difficult and lacks standardized therapeutic regimens. Indigo naturalis has been demonstrated to be safe and effective in treating skin psoriasis. This trial was conducted to evaluate the efficacy and safety of refined indigo naturalis extract in oil (Lindioil) in treating nail psoriasis. Thirty-one outpatients with symmetrically comparable psoriatic nails were enrolled. Lindioil (experimental group) or olive oil (control group) was applied topically to the same subjects' two bilaterally symmetrical psoriatic nails twice daily for the first 12 weeks and then subjects applied Lindioil to both hands for 12 additional weeks. Outcomes were measured using Nail Psoriasis Severity Index (NAPSI) for five nails on one hand and for the single most severely affected nail from either hand. The results show a reduction of NAPSI scores for the 12-week treatment for the Lindioil group (49.8% for one hand and 59.3% for single nail) was superior to the reduction in the scores for the control group (22.9%, 16.3%, respectively). There were no adverse events during the 24 weeks of treatment. This trial demonstrates that Lindioil is a novel, safe and effective therapy for treating nail psoriasis. Copyright © 2014 Elsevier GmbH. All rights reserved.

Advances in heroin addiction treatment with traditional Chinese medicine: a systematic review of recent Chinese language journals.

PubMed

Jordan, James B; Tu, Xiang

2008-01-01

The aim of this review is to critically examine the clinical trial research on Traditional Chinese Medicine (TCM) as an intervention in treating heroin addiction in People's Republic of China. This review examines Chinese-language-only publications for the patent medicines: Shenfu Tuodu, Fukang Pian, and Shifu Sheng. Other compound medicines will be reviewed in future publications. A systematic review of the literature was conducted in Western and Chinese databases. Most trials were excluded because they did not declare randomization and had poor methodology or reporting. The majority of clinical evidence in the random controlled trials demonstrates good evidence for TCM patent medicines in heroin addiction treatment. When compared to typical Western medications, TCMs demonstrate fewer side-effects, in addition to equal measures of treatment efficacy and safety.

A randomized controlled trial of group Stepping Stones Triple P: a mixed-disability trial.

PubMed

Roux, Gemma; Sofronoff, Kate; Sanders, Matthew

2013-09-01

Stepping Stones Triple P (SSTP) is a parenting program designed for families of a child with a disability. The current study involved a randomized controlled trial of Group Stepping Stones Triple P (GSSTP) for a mixed-disability group. Participants were 52 families of children diagnosed with an Autism Spectrum Disorder, Down syndrome, Cerebral Palsy, or an intellectual disability. The results demonstrated significant improvements in parent-reported child behavior, parenting styles, parental satisfaction, and conflict about parenting. Results among participants were similar despite children's differing impairments. The intervention effect was maintained at 6-month follow-up. The results indicate that GSSTP is a promising intervention for a mixed-disability group. Limitations of the study, along with areas for future research, are also discussed. © FPI, Inc.

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis.

PubMed

Lancaster, Lisa H; de Andrade, Joao A; Zibrak, Joseph D; Padilla, Maria L; Albera, Carlo; Nathan, Steven D; Wijsenbeek, Marlies S; Stauffer, John L; Kirchgaessler, Klaus-Uwe; Costabel, Ulrich

2017-12-31

Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequent post hoc analyses have demonstrated that pirfenidone reduces lung function decline, decreases mortality and improves progression-free survival. Long-term extension trials, registries and real-world studies have also shown similar treatment effects with pirfenidone. However, for patients with IPF to obtain the maximum benefits of pirfenidone treatment, the potential adverse events (AEs) associated with pirfenidone need to be managed. This review highlights the well-known and established safety profile of pirfenidone based on randomised controlled clinical trials and real-world data. Key strategies for preventing and managing the most common pirfenidone-related AEs are described, with the goal of maximising adherence to pirfenidone with minimal AEs. Copyright ©ERS 2017.

Benefits of commercial weight-loss programs on blood pressure and lipids: a systematic review.

PubMed

Mehta, Ambereen K; Doshi, Ruchi S; Chaudhry, Zoobia W; Jacobs, David K; Vakil, Rachit M; Lee, Clare J; Bleich, Sara N; Clark, Jeanne M; Gudzune, Kimberly A

2016-09-01

Our objective was to compare the effect of commercial weight-loss programs on blood pressure and lipids to control/education or counseling among individuals with overweight/obesity. We conducted a systematic review by searching MEDLINE and Cochrane Database of Systematic Reviews from inception to November 2014 and references identified by the programs. We included randomized, controlled trials ≥12weeks in duration. Two reviewers extracted information on study design, interventions, and mean change in systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides, and total cholesterol and assessed risk of bias. We included 27 trials. Participants' blood pressure and lipids were normal at baseline in most trials. At 12months, Weight Watchers showed little change in blood pressure or lipid outcomes as compared to control/education (2 trials). At 12months, Atkins' participants had higher HDL-c and lower triglycerides than counseling (4 trials). Other programs had inconsistent effects or lacked long-term studies. Risk of bias was high for most trials of all programs. In conclusion, limited data exist regarding most commercial weight-loss programs' long-term effects on blood pressure and lipids. Clinicians should be aware that Weight Watchers has limited data that demonstrate CVD risk factor benefits relative to control/education. Atkins may be a reasonable option for patients with dyslipidemia. Additional well-designed, long-term trials are needed to confirm these conclusions and evaluate other commercial programs. Copyright © 2016 Elsevier Inc. All rights reserved.

New drugs: evidence relating to their therapeutic value after introduction to the market.

PubMed

Ujeyl, Mariam; Schlegel, Claudia; Walter, Siegbert; Gundert-Remy, Ursula

2012-02-01

Drug approval is based on three criteria: quality, efficacy, and safety. We investigated the types of study design and statistical methods employed to demonstrate safety and efficacy of proprietary medicinal products (PMPs) that were approved for use in the European Union through the centralized procedure. We retrospectively analyzed the European Public Assessment Reports of PMPs that the European Medicinal Agency approved, either initially or for extended indications, in 2009 and 2010. Data were analyzed for 39 PMPs: 64% of these were new active substances, and 36% were approved for extended indications. 46% of the PMPs had been studied in an active-control trial. In only 28%, superiority of the new PMPs compared to active control had been tested. 46% of the approvals included testing of a patient-relevant primary endpoint. The median size of population used to demonstrate safety was 1700 persons. The centralized procedure does not require comparative information from active-control trials. Accordingly, as our descriptive analysis revealed, this information is often not available at the time of market introduction. Pivotal studies only rarely clearly demonstrate an added therapeutic value of a new PMP compared to existing alternatives.

A randomized controlled trial of qigong for fibromyalgia

PubMed Central

2012-01-01

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

Addressing the controversy of rate-versus-rhythm control in atrial fibrillation.

PubMed

Contractor, Tahmeed; Levin, Vadim; Desai, Ravi; Marchlinski, Francis E

2013-09-01

Atrial fibrillation is the most common sustained cardiac arrhythmia and significantly increases patient risk of stroke, cardiomyopathy, and mortality. Rate versus rhythm control as the "best" treatment strategy remains an issue of considerable, ongoing debate. A multitude of clinical trials have compared the 2 strategies and have not shown any benefit of one approach over the other. However, the trials were conducted in specific subgroups of patients and demonstrated low success rates with antiarrhythmic drug (AAD) therapy and a high incidence of adverse AAD effects. Sub-analyses of the trials have confirmed that successful rhythm control with sinus rhythm restoration is associated with a significant reduction in patient mortality. More recently, radiofrequency ablation (RFA) has emerged as a relatively effective procedure for maintaining sinus rhythm compared with use of AADs. Prospective randomized studies have shown good treatment results after the use of RFA, with acceptable risk. Given the limitation of pharmacologic rate versus rhythm control studies, and the promise of RFA, rhythm control should again be reconsidered as the "best" approach for managing many subgroups of patients with atrial fibrillation.

The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial.

PubMed

Berk, Michael; Dean, Olivia; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa S; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Allwang, Christine; Cobb, Heidi; Bush, Ashley I; Schapkaitz, Ian; Dodd, Seetal; Malhi, Gin S

2011-12-01

Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders, including bipolar disorder. This dysregulation may be amenable to therapeutic intervention. Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain, and the most generic of all endogenous antioxidants in terms of action. N-acetylcysteine (NAC) is a glutathione precursor that effectively replenishes brain glutathione. Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy, and the limited efficacy of mood stabilisers in the depressive phase of the disorder, this is a major unmet need. This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a randomised placebo controlled clinical trial of the efficacy of 1g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder. In this trial, the estimated mean baseline Bipolar Depression Rating Scale (BDRS) score was 19.7 (SE=0.8), and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 (SE=0.8). This reduction was statistically significant (p<0.001). Improvements in functioning and quality of life were similarly evident. These open label data demonstrate a robust decrement in depression scores with NAC treatment. Large placebo controlled trials of acute bipolar depression are warranted. Copyright © 2011 Elsevier B.V. All rights reserved.

Field Performance of Bt Eggplants (Solanum melongena L.) in the Philippines: Cry1Ac Expression and Control of the Eggplant Fruit and Shoot Borer (Leucinodes orbonalis Guenée)

PubMed Central

Hautea, Desiree M.; Taylo, Lourdes D.; Masanga, Anna Pauleen L.; Sison, Maria Luz J.; Narciso, Josefina O.; Quilloy, Reynaldo B.; Hautea, Randy A.; Shotkoski, Frank A.; Shelton, Anthony M.

2016-01-01

Plants expressing Cry proteins from the bacterium, Bacillus thuringiensis (Bt), have become a major tactic for controlling insect pests in maize and cotton globally. However, there are few Bt vegetable crops. Eggplant (Solanum melongena) is a popular vegetable grown throughout Asia that is heavily treated with insecticides to control the eggplant fruit and shoot borer, Leucinodes orbonalis (EFSB). Herein we provide the first publicly available data on field performance in Asia of eggplant engineered to produce the Cry1Ac protein. Replicated field trials with five Bt eggplant open-pollinated (OP) lines from transformation event EE-1 and their non-Bt comparators were conducted over three cropping seasons in the Philippines from 2010–2012. Field trials documented levels of Cry1Ac protein expressed in plants and evaluated their efficacy against the primary target pest, EFSB. Cry1Ac concentrations ranged from 0.75–24.7 ppm dry weight with the highest in the terminal leaves (or shoots) and the lowest in the roots. Cry1Ac levels significantly increased from the vegetative to the reproductive stage. Bt eggplant lines demonstrated excellent control of EFSB. Pairwise analysis of means detected highly significant differences between Bt eggplant lines and their non-Bt comparators for all field efficacy parameters tested. Bt eggplant lines demonstrated high levels of control of EFSB shoot damage (98.6–100%) and fruit damage (98.1–99.7%) and reduced EFSB larval infestation (95.8–99.3%) under the most severe pest pressure during trial 2. Moths that emerged from larvae collected from Bt plants in the field and reared in their Bt eggplant hosts did not produce viable eggs or offspring. These results demonstrate that Bt eggplant lines containing Cry1Ac event EE-1 provide outstanding control of EFSB and can dramatically reduce the need for conventional insecticides. PMID:27322533

Motor/Prefrontal Transcranial Direct Current Stimulation (tDCS) Following Lumbar Surgery Reduces Postoperative Analgesia Use.

PubMed

Glaser, John; Reeves, Scott T; Stoll, William David; Epperson, Thomas I; Hilbert, Megan; Madan, Alok; George, Mark S; Borckardt, Jeffrey J

2016-05-01

Randomized, controlled pilot trial. The present study is the first randomized, double-blind, sham-controlled pilot clinical trial of transcranial direct current stimulation (tDCS) for pain and patient-controlled analgesia (PCA) opioid usage among patients receiving spine surgery. Lumbar spinal surgeries are common, and while pain is often a complaint that precedes surgical intervention, the procedures themselves are associated with considerable postoperative pain lasting days to weeks. Adequate postoperative pain control is an important factor in determining recovery and new analgesic strategies are needed that can be used adjunctively to existing strategies potentially to reduce reliance on opioid analgesia. Several novel brain stimulation technologies including tDCS are beginning to demonstrate promise as treatments for a variety of pain conditions. Twenty-seven patients undergoing lumbar spine procedures at Medical University of South Carolina were randomly assigned to receive four 20-minute sessions of real or sham tDCS during their postsurgical hospital stay. Patient-administered hydromorphone usage was tracked along with numeric rating scale pain ratings. The effect of tDCS on the slope of the cumulative PCA curve was significant (P < 0.001) and tDCS was associated with a 23% reduction in PCA usage. In the real tDCS group a 31% reduction was observed in pain-at-its-least ratings from admission to discharge (P = 0.027), but no other changes in numeric rating scale pain ratings were significant in either group. The present pilot trial is the first study to demonstrate an opioid sparing effect of tDCS after spine surgical procedures. Although this was a small pilot trial in a heterogeneous sample of spinal surgery patients, a moderate effect-size was observed for tDCS, suggesting that future work in this area is warranted. 2.

Three-dimensional printed upper-limb prostheses lack randomised controlled trials: A systematic review

PubMed Central

Diment, Laura E; Thompson, Mark S; Bergmann, Jeroen HM

2017-01-01

Background: Three-dimensional printing provides an exciting opportunity to customise upper-limb prostheses. Objective: This review summarises the research that assesses the efficacy and effectiveness of three-dimensional printed upper-limb prostheses. Study design: Systematic review. Methods: PubMed, Web of Science and OVID were systematically searched for studies that reported human trials of three-dimensional printed upper-limb prostheses. The studies matching the language, peer-review and relevance criteria were ranked by level of evidence and critically appraised using the Downs and Black Quality Index. Results: After removing duplicates, 321 records were identified. Eight papers met the inclusion criteria. No studies used controls; five were case studies and three were small case-series studies. All studies showed promising results, but none demonstrated external validity, avoidance of bias or statistically significant improvements over conventional prostheses. The studies demonstrated proof-of-concept rather than assessing efficacy, and the devices were designed to prioritise reduction of manufacturing costs, not customisability for comfort and function. Conclusion: The potential of three-dimensional printing for individual customisation has yet to be fully realised, and the efficacy and effectiveness to be rigorously assessed. Until randomised controlled trials with follow-up are performed, the comfort, functionality, durability and long-term effects on quality of life remain unknown. Clinical relevance Initial studies suggest that three-dimensional printing shows promise for customising low-cost upper-limb prosthetics. However, the efficacy and effectiveness of these devices have yet to be rigorously assessed. Until randomised controlled trials with follow-up are performed, the comfort, functionality, durability and long-term effects on patient quality of life remain unknown. PMID:28649911

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P; Ashford, Robert L

2014-07-29

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P

2016-08-23

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P; Ashford, Robert L

2012-06-13

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. For this fourth update, we searched The Cochrane Wounds Group Specialised Register (searched 27 January 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1); Ovid MEDLINE (2010 to January Week 2 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, January 26, 2012); Ovid EMBASE (2010 to 2012 Week 03); and EBSCO CINAHL (2010 to January 6 2012). All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

Therapeutic touch for healing acute wounds.

PubMed

O'Mathúna, Dónal P

2016-05-03

Therapeutic Touch (TT) is an alternative therapy that has gained popularity over the past two decades for helping wounds to heal. Practitioners enter a meditative state and pass their hands above the patient's body to find and correct any imbalances in the patient's 'life energy' or chi. Scientific instruments have been unable to detect this energy. The effect of TT on wound healing has been expounded in anecdotal publications. To identify and review all relevant data to determine the effects of TT on healing acute wounds. In January 2014, for this fifth update, we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. All randomised or quasi-randomised controlled trials, which compared the effect of TT with a placebo, another treatment, or no treatment control were considered. Studies which used TT as a stand-alone treatment, or as an adjunct to other therapies, were eligible. One author (DO'M) determined the eligibility for inclusion of all trials in the review. Both authors conducted data extraction and evaluation of trial validity independently. Each trial was assessed using predetermined criteria. No new trials were identified for this update. Four trials in people with experimental wounds were included. The effect of TT on wound healing in these studies was variable. Two trials (n = 44 & 24) demonstrated a significant increase in healing associated with TT, while one trial found significantly worse healing after TT and the other found no significant difference. All trials are at high risk of bias. There is no robust evidence that TT promotes healing of acute wounds.

The Immediate Effect of Sildenafil on Right Ventricular Function in Patients with Heart Failure Measured by Cardiac Magnetic Resonance: A Randomized Control Trial

PubMed Central

Durães, André Rodrigues; Borges, Sirlene Mendes; Aras, Roque

2015-01-01

Background Studies have demonstrated that phosphodiesterase 5 (PDE5) inhibition is associated with right ventricle (RV) functional improvement in patients with primary pulmonary hypertension. This study aims to demonstrate the immediate impact of Sildenafil, a PDE5 inhibitor, on RV function, measured by cardiovascular magnetic resonance (CMR), in patients with heart failure (HF). Methods We conducted a randomized double-blind controlled trial. Inclusion criteria: diagnosis of HF functional class I-III; left ventricle ejection fraction < 35%. Patients underwent CMR evaluation and were then equally randomly assigned to either 50 mg of Sildenafil or Placebo groups. One hour following drug administration, they were submitted to a second scan examination. Results 26 patients were recruited from a tertiary reference center in Brazil and 13 were allocated to each study group. The median age was 61.5 years (50–66.5 years). Except for the increase in RV fractional area change following the administration of sildenafil (Sildenafil [before vs. after]: 34.3 [25.2–43.6]% vs. 42.9 [28.5–46.7]%, p = 0.04; Placebo [before vs. after]: 28.1 [9.2–34.8]% vs. 29.2 [22.5–38.8]%, p = 0.86), there was no statistically significant change in parameters. There was no improvement in left ventricular parameters or in the fractional area change of the pulmonary artery. Conclusion This study demonstrated that a single dose of Sildenafil did not significantly improve RV function as measured by the CMR. Trial Registration ClinicalTrials.gov NCT01936350 PMID:25793988

Clinical trials in male hormonal contraception.

PubMed

Nieschlag, Eberhard

2010-11-01

Research has established the principle of hormonal male contraception based on suppression of gonadotropins and spermatogenesis. All hormonal male contraceptives use testosterone, but only in East Asian men can testosterone alone suppress spermatogenesis to a level compatible with contraceptive protection. In Caucasians, additional agents are required of which progestins are favored. Clinical trials concentrate on testosterone combined with norethisterone, desogestrel, etonogestrel or depot-medroxyprogesterone acetate. The first randomized, placebo-controlled clinical trial performed by the pharmaceutical industry demonstrated the effectiveness of a combination of testosterone undecanoate and etonogestrel in suppressing spermatogenesis in volunteers. Copyright © 2010 Elsevier Inc. All rights reserved.

PACE team response shows a disregard for the principles of science.

PubMed

Edwards, Jonathan

2017-08-01

The PACE trial of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome/myalgic encephalomyelitis has raised serious questions about research methodology. An editorial article by Geraghty gives a fair account of the problems involved, if anything understating the case. The response by White et al. fails to address the key design flaw, of an unblinded study with subjective outcome measures, apparently demonstrating a lack of understanding of basic trial design requirements. The failure of the academic community to recognise the weakness of trials of this type suggests that a major overhaul of quality control is needed.

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

PubMed

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

2008-01-01

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

The neural correlates of impaired attentional control in social anxiety: an ERP study of inhibition and shifting.

PubMed

Judah, Matt R; Grant, DeMond M; Mills, Adam C; Lechner, William V

2013-12-01

Cognitive models of social anxiety disorder posit that maladaptive thought processes play an etiological role in symptoms. The current study tested whether socially anxious individuals (HSAs) demonstrated impaired processing efficiency at the neural and behavioral level, and whether this was exacerbated by self-focused attention. Thirty-two (16 socially anxious, 16 nonanxious controls) subjects completed a mixed-antisaccade task with an oddball instructional cue. To manipulate self-focus, participants were told that the oddball cue indicated elevated heart rate. The HSA group demonstrated delayed saccade onset compared with controls, but made fewer errors. HSAs also had lower P3b amplitude compared with controls, suggesting reduced availability of resources for discriminating cues, and later P3b latency during self-focus trials, suggesting delayed cue categorization. Additionally, HSAs had greater CNV negativity compared with controls, suggesting greater effort in response preparation, and this negativity was reduced during self-focus trials, supporting the hypothesis that self-focused attention preoccupies executive resources. The current study supports and expands cognitive theories by documenting impaired neural and behavioral functioning in social anxiety and the role of self-focused attention in these deficits.

Efficacy of the resilience and adjustment intervention after traumatic brain injury: a randomized controlled trial.

PubMed

Kreutzer, Jeffrey S; Marwitz, Jennifer H; Sima, Adam P; Mills, Ana; Hsu, Nancy H; Lukow, Herman R

2018-05-24

Examine a psychoeducational and skill-building intervention's effectiveness for individuals after traumatic brain injury (TBI), using a two-arm, parallel, randomized, controlled trial with wait-listed control. The Resilience and Adjustment Intervention (RAI) targets adjustment challenges and emphasizes education, skill-building and psychological support. Overall, 160 outpatients were randomly assigned to a treatment or wait-list control (WLC) group. The manualized treatment was delivered in seven 1-h sessions. The Connor-Davidson Resilience Scale (CD-RISC) was the primary outcome measure. Secondary measures included the Mayo Portland Adaptability Inventory-4 (MPAI-4), Brief Symptom Inventory-18 (BSI-18) and 13-Item Stress Test. After adjusting for injury severity, education and time postinjury, the RAI group (N = 75) demonstrated a significantly greater increase in resilience (effect size = 1.03) compared to the WLC group (N = 73). Participants in the RAI group demonstrated more favourable scores on the MPAI-4 Adjustment and Ability Indices, BSI-18 and the 13-item Stress Test. However, only the CD-RISC and BSI-18 demonstrated a clinically significant difference. In addition, RAI participants demonstrated maintenance of gains from pre-treatment to 3-month follow-up; however, only the BSI-18 maintained a clinically significant difference. Investigation provided evidence that a resilience-focused intervention can improve psychological health and adjustment after TBI. Additional research is needed to ascertain the longer term benefits of intervention and the efficacy of alternative delivery methods (e.g., via telephone, Internet).

Gaze-Contingent Music Reward Therapy for Social Anxiety Disorder: A Randomized Controlled Trial.

PubMed

Lazarov, Amit; Pine, Daniel S; Bar-Haim, Yair

2017-07-01

Patients with social anxiety disorder exhibit increased attentional dwelling on social threats, providing a viable target for therapeutics. This randomized controlled trial examined the efficacy of a novel gaze-contingent music reward therapy for social anxiety disorder designed to reduce attention dwelling on threats. Forty patients with social anxiety disorder were randomly assigned to eight sessions of either gaze-contingent music reward therapy, designed to divert patients' gaze toward neutral stimuli rather than threat stimuli, or to a control condition. Clinician and self-report measures of social anxiety were acquired pretreatment, posttreatment, and at 3-month follow-up. Dwell time on socially threatening faces was assessed during the training sessions and at pre- and posttreatment. Gaze-contingent music reward therapy yielded greater reductions of symptoms of social anxiety disorder than the control condition on both clinician-rated and self-reported measures. Therapeutic effects were maintained at follow-up. Gaze-contingent music reward therapy, but not the control condition, also reduced dwell time on threat, which partially mediated clinical effects. Finally, gaze-contingent music reward therapy, but not the control condition, also altered dwell time on socially threatening faces not used in training, reflecting near-transfer training generalization. This is the first randomized controlled trial to examine a gaze-contingent intervention in social anxiety disorder. The results demonstrate target engagement and clinical effects. This study sets the stage for larger randomized controlled trials and testing in other emotional disorders.

Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

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

Yamoah, Kosj; Showalter, Timothy N.; Ohri, Nitin, E-mail: ohri.nitin@gmail.com

Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: Inmore » primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.« less

Abdominal massage for neurogenic bowel dysfunction in people with multiple sclerosis (AMBER - Abdominal Massage for Bowel Dysfunction Effectiveness Research): study protocol for a randomised controlled trial.

PubMed

McClurg, Doreen; Goodman, Kirsteen; Hagen, Suzanne; Harris, Fional; Treweek, Sean; Emmanuel, Anton; Norton, Christine; Coggrave, Maureen; Doran, Selina; Norrie, John; Donnan, Peter; Mason, Helen; Manoukian, Sarkis

2017-03-29

Multiple sclerosis (MS) is a life-long condition primarily affecting younger adults. Neurogenic bowel dysfunction (NBD) occurs in 50-80% of these patients and is the term used to describe constipation and faecal incontinence, which often co-exist. Data from a pilot study suggested feasibility of using abdominal massage for the relief of constipation, but the effectiveness remains uncertain. This is a multi-centred patient randomised superiority trial comparing an experimental strategy of once daily abdominal massage for 6 weeks against a control strategy of no massage in people with MS who have stated that their constipation is bothersome. The primary outcome is the Neurogenic Bowel Dysfunction Score at 24 weeks. Both groups will receive optimised advice plus the MS Society booklet on bowel management in MS, and will continue to receive usual care. Participants and their clinicians will not be blinded to the allocated intervention. Outcome measures are primarily self-reported and submitted anonymously. Central trial staff who will manage and analyse the trial data will be unaware of participant allocations. Analysis will follow intention-to-treat principles. This pragmatic randomised controlled trial will demonstrate if abdominal massage is an effective, cost-effective and viable addition to the treatment of NBD in people with MS. ClinicalTrials.gov, ISRCTN85007023 . Registered on 10 June 2014.

Blood and Marrow Transplant Clinical Trials Network Report on the Development of Novel Endpoints and Selection of Promising Approaches for Graft-versus-Host Disease Prevention Trials.

PubMed

Pasquini, Marcelo C; Logan, Brent; Jones, Richard J; Alousi, Amin M; Appelbaum, Frederick R; Bolaños-Meade, Javier; Flowers, Mary E D; Giralt, Sergio; Horowitz, Mary M; Jacobsohn, David; Koreth, John; Levine, John E; Luznik, Leo; Maziarz, Richard; Mendizabal, Adam; Pavletic, Steven; Perales, Miguel-Angel; Porter, David; Reshef, Ran; Weisdorf, Daniel; Antin, Joseph H

2018-06-01

Graft-versus-host disease (GVHD) is a common complication after hematopoietic cell transplantation (HCT) and associated with significant morbidity and mortality. Preventing GVHD without chronic therapy or increasing relapse is a desired goal. Here we report a benchmark analysis to evaluate the performance of 6 GVHD prevention strategies tested at single institutions compared with a large multicenter outcomes database as a control. Each intervention was compared with the control for the incidence of acute and chronic GVHD and overall survival and against novel composite endpoints: acute and chronic GVHD, relapse-free survival (GRFS), and chronic GVHD, relapse-free survival (CRFS). Modeling GRFS and CRFS using the benchmark analysis further informed the design of 2 clinical trials testing GVHD prophylaxis interventions. This study demonstrates the potential benefit of using an outcomes database to select promising interventions for multicenter clinical trials and proposes novel composite endpoints for use in GVHD prevention trials. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Expanding the Evidence Base: Comparing Randomized Controlled Trials and Observational Studies of Statins.

PubMed

Atar, Dan; Ong, Seleen; Lansberg, Peter J

2015-01-01

It is widely accepted that randomized controlled trials (RCTs) are the gold standard for demonstrating the efficacy of a given therapy (results under ideal conditions). Observational studies, on the other hand, can complement this by demonstrating effectiveness (results under real-world conditions). To examine the role that observational studies can play in complementing data from RCTs, we reviewed published studies for statins, a class of drugs that have been widely used to reduce the risk of cardiovascular (CV) events by lowering low-density lipoprotein cholesterol levels. RCTs have consistently demonstrated the benefits of statin treatment in terms of CV risk reduction and have demonstrated that more intensive statin therapy has incremental benefits over less intensive treatment. Observational studies of statin use in 'real-world' populations have served to augment the evidence base generated from statin RCTs in preselected populations of patients who are often at high CV risk and have led to similar safety and efficacy findings. They have also raised questions about factors affecting medication adherence, under-treatment, switching between statins, and failure to reach low-density lipoprotein cholesterol target levels, questions for which the answers could lead to improved patient care.

Design of a multi-arm randomized clinical trial with no control arm.

PubMed

Magaret, Amalia; Angus, Derek C; Adhikari, Neill K J; Banura, Patrick; Kissoon, Niranjan; Lawler, James V; Jacob, Shevin T

2016-01-01

Clinical trial designs that include multiple treatments are currently limited to those that perform pairwise comparisons of each investigational treatment to a single control. However, there are settings, such as the recent Ebola outbreak, in which no treatment has been demonstrated to be effective; and therefore, no standard of care exists which would serve as an appropriate control. For illustrative purposes, we focused on the care of patients presenting in austere settings with critically ill 'sepsis-like' syndromes. Our approach involves a novel algorithm for comparing mortality among arms without requiring a single fixed control. The algorithm allows poorly-performing arms to be dropped during interim analyses. Consequently, the study may be completed earlier than planned. We used simulation to determine operating characteristics for the trial and to estimate the required sample size. We present a potential study design targeting a minimal effect size of a 23% relative reduction in mortality between any pair of arms. Using estimated power and spurious significance rates from the simulated scenarios, we show that such a trial would require 2550 participants. Over a range of scenarios, our study has 80 to 99% power to select the optimal treatment. Using a fixed control design, if the control arm is least efficacious, 640 subjects would be enrolled into the least efficacious arm, while our algorithm would enroll between 170 and 430. This simulation method can be easily extended to other settings or other binary outcomes. Early dropping of arms is efficient and ethical when conducting clinical trials with multiple arms. Copyright © 2015 Elsevier Inc. All rights reserved.

Empowered Diabetes Management: Life Coaching and Pharmacist Counseling for Employed Adults with Diabetes

ERIC Educational Resources Information Center

Nishita, Christy; Cardazone, Gina; Uehara, Denise Lea; Tom, Tammy

2013-01-01

The Hawai'i Demonstration to Maintain Independence and Employment was a randomized controlled trial examining the effect of a participant-driven, multicomponent intervention on 190 employed adults with diabetes, 36% of whom were Asian and 35% of whom were Native Hawaiian or Pacific Islander. A no treatment concurrent control group was used, and…

Positive Outlook as a Moderator of the Effectiveness of an HIV/STI Intervention with Adolescents in Detention

ERIC Educational Resources Information Center

Schmiege, Sarah J.; Ewing, Sarah W. Feldstein; Hendershot, Christian S.; Bryan, Angela D.

2011-01-01

Justice-involved adolescents engage in high levels of risky sexual behavior, underscoring the need for targeted, effective, prevention interventions geared toward this population. In a randomized controlled trial, 484 detained adolescents received a theory-based intervention or an information-only control. We have previously demonstrated that the…

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

PubMed

Sandilands, Euan A; Cameron, Sharon; Paterson, Frances; Donaldson, Sam; Briody, Lesley; Crowe, Jane; Donnelly, Julie; Thompson, Adrian; Johnston, Neil R; Mackenzie, Ivor; Uren, Neal; Goddard, Jane; Webb, David J; Megson, Ian L; Bateman, Nicholas; Eddleston, Michael

2012-02-03

Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

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

PubMed Central

Brunwasser, Steven M.; Garber, Judy

2015-01-01

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

Effects of web-based instruction and patient preferences on patient-reported outcomes and learning for women with advanced ovarian cancer: A randomized controlled trial.

PubMed

Petzel, Sue V; Isaksson Vogel, Rachel; Cragg, Julie; McClellan, Molly; Chan, Daniel; Jacko, Julie A; Sainfort, François; Geller, Melissa A

2018-05-23

A randomized controlled trial was conducted of a web-based intervention to improve advanced care planning in women with ovarian cancer. A secondary analysis of 35 randomized women focused on changes in distress and knowledge about ovarian cancer through distress monitoring and information tailored to patients' cognitive coping style (monitoring, blunting). Pre-/postresults indicated the Intervention group demonstrated lower distress (p = 0.06); blunting was associated with lower depression (p = 0.04); knowledge in both groups was unchanged. Women in the Intervention vs. Control group reported their family was less likely to be upset by cancer information (p = 0.0004). This intervention reduced distress while incorporating patient preferences.

Vitamins and abdominal aortic aneurysm.

PubMed

Takagi, Hisato; Umemoto, Takuya

2017-02-01

To summarize the association of vitamins (B6, B12, C, D, and E) and abdominal aortic aneurysm (AAA), we reviewed clinical studies with a comprehensive literature research and meta-analytic estimates. To identify all clinical studies evaluating the association of vitamins B6/B12/C/D/E and AAA, databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through April 2015, using Web-based search engines (PubMed and OVID). For each case-control study, data regarding vitamin levels in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Pooled analyses of the 4 case-control studies demonstrated significantly lower circulating vitamin B6 levels (SMD, -0.33; 95% CI, -0.55 to -0.11; P=0.003) but non-significantly lower vitamin B12 levels (SMD, -0.42; 95% CI, -1.09 to 0.25; P=0.22) in patients with AAA than subjects without AAA. Pooled analyses of the 2 case-control studies demonstrated significantly lower levels of circulating vitamins C (SMD, -0.71; 95% CI, -1.23 to -0.19; P=0.007) and E (SMD, -1.76; 95% CI, -2.93 to 0.60; P=0.003) in patients with AAA than subjects without AAA. Another pooled analysis of the 3 case-control studies demonstrated significantly lower circulating vitamin D (25-hydroxyvitamin D) levels (SMD, -0.25; 95% CI, -0.50 to -0.01; P=0.04) in patients with AAA than subjects without AAA. In a double-blind controlled trial, 4.0-year treatment with a high-dose folic acid and vitamin B6/B12 multivitamin in kidney transplant recipients did not reduce a rate of AAA repair despite significant reduction in homocysteine level. In another randomized, double-blind, placebo-controlled trial, 5.8-year supplementation with α-tocopherol (vitamin E) had no preventive effect on large AAA among male smokers. In clinical setting, although low circulating vitamins B6/C/D/E (not B12) levels are associated with AAA presence, vitamins B6/B12/E supplementation may not reduce AAA incidence.

Increased susceptibility to proactive interference in adults with dyslexia?

PubMed

Bogaerts, Louisa; Szmalec, Arnaud; Hachmann, Wibke M; Page, Mike P A; Woumans, Evy; Duyck, Wouter

2015-01-01

Recent findings show that people with dyslexia have an impairment in serial-order memory. Based on these findings, the present study aimed to test the hypothesis that people with dyslexia have difficulties dealing with proactive interference (PI) in recognition memory. A group of 25 adults with dyslexia and a group of matched controls were subjected to a 2-back recognition task, which required participants to indicate whether an item (mis)matched the item that had been presented 2 trials before. PI was elicited using lure trials in which the item matched the item in the 3-back position instead of the targeted 2-back position. Our results demonstrate that the introduction of lure trials affected 2-back recognition performance more severely in the dyslexic group than in the control group, suggesting greater difficulty in resisting PI in dyslexia.

Implantable hemodynamic monitoring (the Chronicle IHM system): remote telemonitoring for patients with heart failure.

PubMed

Ho, C

2008-01-01

(1) Remote monitoring for ambulatory heart failure patients uses an implantable device to record hemodynamic data and transmit it to a central server for continuous assessment. (2) Preliminary evidence from observational studies suggests a potential for reducing hospitalizations with the use of right ventricle implantable hemodynamic monitoring (IHM). However, although a multicentre, randomized controlled trial (COMPASS-HF) showed a reduction in hospitalizations in the IHM group the results were not statistically significant and the US Food and Drug Administration panel concluded the trial failed to meet its primary efficacy endpoint. (3) In the COMPASS-HF study the most common device-related complication was lead dislodgement. (4) Large randomized controlled trials are needed to demonstrate the clinical utility of IHM, particularly in terms of its impact on reducing hospitalization and improving patient outcomes.

Implementation of the Exception from Informed Consent Regulations in a Large Multicenter Emergency Clinical Trials Network; the RAMPART Experience

PubMed Central

Silbergleit, Robert; Biros, Michelle H.; Harney, Deneil; Dickert, Neal; Baren, Jill

2012-01-01

Clinical trials investigating therapies for acutely and critically ill and injured patients in the earliest phases of treatment often can only be performed under regulations allowing for exception from informed consent (EFIC) for emergency research. Implementation of these regulations in multicenter clinical trials involves special challenges and opportunities. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), the first EFIC trial conducted by the Neurological Emergencies Treatment Trials (NETT) network, combined centralized resources and coordination with retention of local control and flexibility to facilitate compliance with the EFIC regulations. Specific methods used by the NETT included common tools for community consultation and public disclosure, sharing of experiences and knowledge, and reporting of aggregate results. Tracking of community consultation and public disclosure activities and feedback facilitates empirical research on EFIC methods in the network and supports quality improvements for future NETT trials. The NETT model used in RAMPART demonstrates how EFIC may be effectively performed in established clinical trial networks. PMID:22506949

The rate of decline of joint space width in patients with osteoarthritis of the knee: a systematic review and meta-analysis of randomized placebo-controlled trials of chondroitin sulfate .

PubMed

Hochberg, Marc C; Zhan, Min; Langenberg, Patricia

2008-11-01

Chondroitin sulfate has been shown to relieve pain and improve functional limitation in patients with osteoarthritis (OA) of the knee in numerous clinical trials and meta-analyses. Its role as a potential structure-modifying drug for knee OA, however, remains controversial. To perform a meta-analysis of randomized double-blind placebo-controlled clinical trials to assess the efficacy of chondroitin sulfate as a structure-modifying drug for knee OA. A Medline search was conducted from 1996 through 2007 and five articles that reported results from three trials were identified; one additional trial was identified through review of presentations at annual rheumatology meetings. There was no evidence of heterogeneity across the trials and results were pooled using a fixed effects meta-analysis. Pooled results demonstrated a small significant effect of chondroitin sulfate on the reduction in rate of decline in minimum joint space width of 0.07 mm/year (95% CI 0.03, 0.10) that corresponded to an effect size of 0.26 (95% CI 0.14, 0.38) (p < 0.0001). This result was robust in sensitivity analyses. The individual studies included in the meta-analysis varied in the number of patients enrolled and the techniques used to acquire knee radiographs and to measure joint space width. These results demonstrate that chondroitin sulfate is effective for reducing the rate of decline in minimum joint space width in patients with OA of the knee. Chondroitin sulfate may have a role as a structure-modifying agent in the management of patients with knee OA.

GENERALIZATION OF TREADMILL-SLIP TRAINING TO PREVENT A FALL FOLLLOWING A SUDDEN (NOVEL) SLIP IN OVER-GROUND WALKING

PubMed Central

Yang, Feng; Bhatt, Tanvi; Pai, Yi-Chung

2012-01-01

The purposes of the study were to determine 1) whether treadmill-slip training could reduce the likelihood of falls during a novel slip in over-ground walking, and 2) to what extent such (indirect) training would be comparable to (direct) over-ground-slip training. A treadmill-slip training group (Group A, n=17) initially experienced repeated perturbations on treadmill intended to simulate forward-slip in over-ground walking. Perturbation continued and its intensity reduced when necessary to ensure subjects’ successful adaptation (i.e., when they could land their trailing foot ahead of the slipping foot in at least 3 of 5 consecutive trials). They then experienced a novel slip during over-ground walking. Another 17 young adults in Group B experienced an identical novel slip that served as the controls. They then underwent more slip trials during over-ground walking. Their 16th slip trial was analyzed to represent the over-ground-slip training effect. Eight subjects (47%) in Group A fell upon their first treadmill slip, while all adapted successfully after a minimum of 15 slip trials. Upon the novel slip during over-ground walking, none of them fell in comparison to four subjects (23.5%) fell in Group B upon the same trial (p<0.05). Group A’s control of stability, both proactive and reactive, was significantly better than that of Group B’s on their first over-ground slip, while the level of improvement derived from indirect treadmill training was not as strong as that from direct over-ground-slip training, as demonstrated in Group B’s 16th slip trial (p<0.001). These results clearly demonstrated the feasibility of fall reduction through treadmill-slip training. PMID:23141636

Antimicrobial drugs for persistent diarrhoea of unknown or non-specific cause in children under six in low and middle income countries: systematic review of randomized controlled trials

PubMed Central

2009-01-01

Background A high proportion of children with persistent diarrhoea in middle and low income countries die. The best treatment is not clear. We conducted a systematic review to evaluate the effectiveness of antimicrobial drug treatment for persistent diarrhoea of unknown or non-specific cause. Methods We included randomized comparisons of antimicrobial drugs for the treatment of persistent diarrhoea of unknown or non-specific cause in children under the age of six years in low and middle income countries. We searched the electronic databases MEDLINE, EMBASE, LILACS, WEB OF SCIENCE, and the Cochrane Central Register of Controlled Trials (CENTRAL) to May 2008 for relevant randomized or quasi randomized controlled trials. We summarised the characteristics of the eligible trials, assessed their quality using standard criteria, and extracted relevant outcomes data. Where appropriate, we combined the results of different trials. Results Three trials from South East Asia and one from Guatemala were included, all were small, and three had adequate allocation concealment. Two were in patients with diarrhoea of unknown cause, and two were in patients in whom known bacterial or parasitological causes of diarrhoea had been excluded. No difference was demonstrated for oral gentamicin compared with placebo (presence of diarrhoea at 6 or 7 days; 2 trials, n = 151); and for metronidazole compared with placebo (presence of diarrhoea at 3, 5 and 7 days; 1 trial, n = 99). In one small trial, sulphamethoxazole-trimethoprim appeared better than placebo in relation to diarrhoea at seven days and total stool volume (n = 55). Conclusion There is little evidence as to whether or not antimicrobials help treat persistent diarrhoea in young children in low and middle income countries. PMID:19257885

The Anxiolytic Effect of Midazolam in Third Molar Extraction: A Systematic Review

PubMed Central

Chen, Qi; Wang, Lufei; Ge, Lina; Gao, Yuan; Wang, Hang

2015-01-01

Purpose To assess the efficacy of midazolam for anxiety control in third molar extraction surgery. Methods Electronic retrievals were conducted in Medline (via PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12), and the System for Information on Grey Literature in Europe (SIGLE). The bibliographies of relevant clinical trials were also checked. Randomized controlled trials satisfying the inclusion criteria were evaluated, with data extraction done independently by two well-trained investigators. Disagreements were resolved by discussion or by consultation with a third member of the review team. Results Ten studies were included, but meta-analysis could not be conducted because of the significant differences among articles. All but one article demonstrated that midazolam could relieve anxiety. One article demonstrated that propofol offered superior anxiolysis, with more rapid recovery than with midazolam. Compared with lorazepam and diazepam, midazolam did not distinctly dominate in its sedative effect, but was safer. Two articles used midazolam in multidrug intravenous sedation and proved it to be more effective than midazolam alone. Conclusion It was found, by comparison and analysis, that midazolam might be effective for use for anxiety control during third molar extraction and can be safely administered by a dedicated staff member. It can also be used with other drugs to obtain better sedative effects, but the patient’s respiratory function must be monitored closely, because multidrug sedation is also more risky. PMID:25849859

The anxiolytic effect of midazolam in third molar extraction: a systematic review.

PubMed

Chen, Qi; Wang, Lufei; Ge, Lina; Gao, Yuan; Wang, Hang

2015-01-01

To assess the efficacy of midazolam for anxiety control in third molar extraction surgery. Electronic retrievals were conducted in Medline (via PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12), and the System for Information on Grey Literature in Europe (SIGLE). The bibliographies of relevant clinical trials were also checked. Randomized controlled trials satisfying the inclusion criteria were evaluated, with data extraction done independently by two well-trained investigators. Disagreements were resolved by discussion or by consultation with a third member of the review team. Ten studies were included, but meta-analysis could not be conducted because of the significant differences among articles. All but one article demonstrated that midazolam could relieve anxiety. One article demonstrated that propofol offered superior anxiolysis, with more rapid recovery than with midazolam. Compared with lorazepam and diazepam, midazolam did not distinctly dominate in its sedative effect, but was safer. Two articles used midazolam in multidrug intravenous sedation and proved it to be more effective than midazolam alone. It was found, by comparison and analysis, that midazolam might be effective for use for anxiety control during third molar extraction and can be safely administered by a dedicated staff member. It can also be used with other drugs to obtain better sedative effects, but the patient's respiratory function must be monitored closely, because multidrug sedation is also more risky.

Does Mass Azithromycin Distribution Impact Child Growth and Nutrition in Niger? A Cluster-Randomized Trial

PubMed Central

Amza, Abdou; Yu, Sun N.; Kadri, Boubacar; Nassirou, Baido; Stoller, Nicole E.; Zhou, Zhaoxia; West, Sheila K.; Bailey, Robin L.; Gaynor, Bruce D.; Keenan, Jeremy D.; Porco, Travis C.; Lietman, Thomas M.

2014-01-01

Background Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth. Methodology In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC) in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6–60 months of age. Principal Findings We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49). Conclusions/Significance We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association. PMID:25210836

Cognitive impairment and PD patients' capacity to consent to research

PubMed Central

Cary, Mark; Moelter, Stephen T.; Siderowf, Andrew; Sullo, Elizabeth; Xie, Sharon; Weintraub, Daniel

2013-01-01

Objective: To examine how cognitive impairment affects Parkinson disease (PD) patients' research consent capacity. Methods: A cross-sectional study of 90 patients with PD, divided using Mattis Dementia Rating Scale–2 scores into 3 groups of 30 (normal, borderline, and impaired), and 30 neurologically normal older adults completed 2 capacity interviews (an early-phase randomized and controlled drug trial and a sham-controlled surgical implantation of genetic tissue) using the MacArthur Competence Assessment Tool for Clinical Research. Expert clinicians used the interviews to classify the patients as either capable or not capable of providing their own informed consent. These judgments were compared with performance on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Results: Cognitively normal PD patients typically scored well on the capacity measures. In contrast, patients with impaired cognition were not capable of providing their own informed consent: 17% (5/30) on the drug trial and 3% (1/30) on the surgery trial were judged capable. Patients with borderline impairment showed adequate performance on measures of appreciation and reasoning, but impaired performance on understanding the drug trial compared with normal controls and normal PD patients, and on understanding the surgery trial compared with normal controls. Sixty-seven percent (20/30) on the drug trial and 57% (17/30) on the surgery trial were judged capable of consent. Receiver operating characteristic analyses showed that the MMSE and MoCA could detect the likelihood of impaired capacity, with the MoCA demonstrating greater sensitivity. Conclusions: PD patients with borderline cognitive impairment have impairments in their decisional capacity. The MoCA may be useful to identify the patients at risk of impaired capacity. PMID:23892706

Using an internet intervention to support self-management of low back pain in primary care: findings from a randomised controlled feasibility trial (SupportBack)

PubMed Central

Geraghty, Adam W A; Stanford, Rosie; Stuart, Beth; Little, Paul; Roberts, Lisa C; Foster, Nadine E; Hill, Jonathan C; Hay, Elaine M; Turner, David; Malakan, Wansida; Leigh, Linda; Yardley, Lucy

2018-01-01

Objective To determine the feasibility of a randomised controlled trial of an internet intervention for low back pain (LBP) using three arms: (1) usual care, (2) usual care plus an internet intervention or (3) usual care plus an internet intervention with additional physiotherapist telephone support. Design and setting A three-armed randomised controlled feasibility trial conducted in 12 general practices in England. Participants Primary care patients aged over 18 years, with current LBP, access to the internet and without indicators of serious spinal pathology or systemic illness. Interventions The ‘SupportBack’ internet intervention delivers a 6-week, tailored programme, focused on graded goal setting, self-monitoring and provision of tailored feedback to encourage physical activity. Additional physiotherapist telephone support consisted of three brief telephone calls over a 4-week period, to address any concerns and provide reassurance. Outcomes The primary outcomes were the feasibility of the trial design including recruitment, adherence and retention at follow-up. Secondary descriptive and exploratory analyses were conducted on clinical outcomes including LBP-related disability at 3 months follow-up. Results Primary outcomes: 87 patients with LBP were recruited (target 60–90) over 6 months, and there were 3 withdrawals. Adherence to the intervention was higher in the physiotherapist-supported arm, compared with the stand-alone internet intervention. Trial physiotherapists adhered to the support protocol. Overall follow-up rate on key clinical outcomes at 3 months follow-up was 84%. Conclusions This study demonstrated the feasibility of a future definitive randomised controlled trial to determine the clinical and cost-effectiveness of the SupportBack intervention in primary care patients with LBP. Trial registration number ISRCTN31034004; Results. PMID:29525768

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

PubMed Central

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

2015-01-01

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

Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial

PubMed Central

Popov, Jelena

2017-01-01

Introduction Ulcerative colitis (UC) is a chronic, relapsing condition characterised by colonic inflammation. Increasing prevalence in early-age diagnosis provides opportunities for additional complications in later life as a result of prolonged exposure to inflammatory and therapeutic insults, necessitating novel avenues for therapeutics which may result in fewer side effects. Faecal microbiota transplantation (FMT) has previously demonstrated potential therapeutic benefit in an adult randomised-controlled trial and several recurrent Clostridium difficile infection studies. This phase Ib pilot will be the first randomised, single-blinded, placebo-controlled trial to assess feasibility and patient outcomes in a paediatric inflammatory bowel disease (IBD) population. Methods and analysis Fifty patients will be randomised 1:1 to receive normal saline control or active sample. Enema administrations will be performed two times per week for 6 weeks, followed at a 6-month follow-up period. Feasibility outcomes will include measures of patient eligibility, recruitment, willingness to participate, samples collections, hospitalizations and drop-out rate. Improvements in disease symptoms will determine the efficacy of treatment. Clinical disease scores will be taken throughout the study period using the Paediatric Ulcerative Colitis Activity Index (PUCAI). Monitoring of inflammatory markers in blood and stool will be performed at regular intervals. Microbiome analysis will be conducted on stool samples collected throughout the trials period. Imaging and endoscopic surveillance will be conducted if clinically necessary. Ethics and dissemination Ethics was obtained from local hospital research ethics boards across all three sites. Health Canada and FDA approval was obtained for the use of an Investigatory New Drug product. Results from this trial will be presented in international conferences and published in peer-review journals. Trial registration number Trial registration number: NCT02487238; preresults. PMID:28827258

Immediate pre-meal water ingestion decreases voluntary food intake in lean young males.

PubMed

Corney, Robert A; Sunderland, Caroline; James, Lewis J

2016-03-01

Consuming 375-500 ml of water 30 min before a meal has been shown to reduce energy intake in older, but not younger adults. This study investigated the effects of ingesting a water preload immediately pre-meal (<1 min before eating) on within-meal ad libitum energy intake in non-obese young males. Fourteen healthy males [mean (SD) age 27 (3) years, height 1.83 (0.05) m, body weight 80.47 (9.89) kg, body fat 17.5 (4.0) %, body mass index 24.0 (2.5) kg/m(2)] completed a familiarisation trial and two experimental trials in randomised counterbalanced order. Subjects arrived at the laboratory overnight fasted and consumed an ad libitum porridge breakfast. Immediately prior to the meal, subjects consumed either a 568 ml (1 pint) water preload (preload trial) or no preload (control trial). Visual analogue scale questionnaires to assess hunger, fullness and satisfaction were completed before and after the meal in both trials, as well as after the water preload. Ad libitum energy intake was greater (P < 0.001) during control [2551 (562) kJ] than preload [1967 (454) kJ]. Ad libitum water intake was also greater (P < 0.001) during control [318 (226-975) ml] than preload [116 (0-581) ml]. The water preload increased fullness and satisfaction and decreased hunger compared to pre-trial (P < 0.001) and the control trial (P < 0.001). This study demonstrates that consumption of a 568 ml water preload immediately before a meal reduces energy intake in non-obese young males. This might therefore be an effective strategy to suppress energy intake in this population and possibly assist with weight management.

Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the reverse of the Will Rogers phenomenon?

PubMed

Fokas, Emmanouil; Liersch, Torsten; Fietkau, Rainer; Hohenberger, Werner; Hess, Clemens; Becker, Heinz; Sauer, Rolf; Wittekind, Christian; Rödel, Claus

2015-06-01

Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes. © 2015 American Cancer Society.

Examining Changes to Center of Pressure During the First Trials of Wii Gameplay.

PubMed

Reed-Jones, Rebecca; Carvalho, Laura; Sanderson, Chelsey; Montelpare, William; Murray, Nicholas; Powell, Douglas

2017-02-01

Use of the Nintendo Wii™ as a balance assessment and rehabilitation tool continues to grow. One advantage of the Wii is that games can serve as a virtual reality training tool; however, a disadvantage of the Wii is the human-machine interface and the learning effect over multiple trials. The purpose of this study was to assess changes in postural control during Wii gameplay over a series of trials in novice players. Thirty-one university athletes (aged 18-25 years) completed four trials of the Nintendo Wii Fit™ soccer heading (SH) balance game. Center of pressure (COP) was calculated in the anterior-posterior (AP) and medial-lateral (ML) directions for each 70-second time trial at 1000 Hz. COP was assessed using six linear and two nonlinear measures. Repeated measures analysis of variances compared COP measures over the four trials. Significant differences in COP magnitude and velocity were found between trials 1 and 2 in the ML direction. No significant effects of trial were found in the AP direction. In contrast, a measure of the overall area of COP using an ellipse method revealed a significant reduction to COP area between trials 3 and 4. No significant differences between trials were observed in nonlinear measures. These results demonstrate how magnitude and velocity measures of COP control stabilize after the first trial of Wii SH game play in novice young adults. As Wii rehabilitation focuses on individuals with balance difficulties, an important consideration when using the game as an assessment tool is that more than four trials may be required to capture learning in these populations. In addition, contrasting results from ellipse measurement methods point to the use of multiple measures for robust description of COP behavior. This work provides understanding of normative postural control responses with further research in clinical populations needed.

Regression-based pediatric norms for the brief visuospatial memory test: revised and the symbol digit modalities test.

PubMed

Smerbeck, A M; Parrish, J; Yeh, E A; Hoogs, M; Krupp, Lauren B; Weinstock-Guttman, B; Benedict, R H B

2011-04-01

The Brief Visuospatial Memory Test - Revised (BVMTR) and the Symbol Digit Modalities Test (SDMT) oral-only administration are known to be sensitive to cerebral disease in adult samples, but pediatric norms are not available. A demographically balanced sample of healthy control children (N = 92) ages 6-17 was tested with the BVMTR and SDMT. Multiple regression analysis (MRA) was used to develop demographically controlled normative equations. This analysis provided equations that were then used to construct demographically adjusted z-scores for the BVMTR Trial 1, Trial 2, Trial 3, Total Learning, and Delayed Recall indices, as well as the SDMT total correct score. To demonstrate the utility of this approach, a comparison group of children with acute disseminated encephalomyelitis (ADEM) or multiple sclerosis (MS) were also assessed. We find that these visual processing tests discriminate neurological patients from controls. As the tests are validated in adult multiple sclerosis, they are likely to be useful in monitoring pediatric onset multiple sclerosis patients as they transition into adulthood.

Effect of intervention programs in schools to reduce screen time: a meta-analysis.

PubMed

Friedrich, Roberta Roggia; Polet, Jéssica Pinto; Schuch, Ilaine; Wagner, Mário Bernardes

2014-01-01

to evaluate the effects of intervention program strategies on the time spent on activities such as watching television, playing videogames, and using the computer among schoolchildren. a search for randomized controlled trials available in the literature was performed in the following electronic databases: PubMed, Lilacs, Embase, Scopus, Web of Science, and Cochrane Library using the following Keywords randomized controlled trial, intervention studies, sedentary lifestyle, screen time, and school. A summary measure based on the standardized mean difference was used with a 95% confidence interval. a total of 1,552 studies were identified, of which 16 were included in the meta-analysis. The interventions in the randomized controlled trials (n=8,785) showed a significant effect in reducing screen time, with a standardized mean difference (random effect) of: -0.25 (-0.37, -0.13), p<0.01. interventions have demonstrated the positive effects of the decrease of screen time among schoolchildren. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Hypnosis for procedure-related pain and distress in pediatric cancer patients: a systematic review of effectiveness and methodology related to hypnosis interventions.

PubMed

Richardson, Janet; Smith, Joanna E; McCall, Gillian; Pilkington, Karen

2006-01-01

The aim of this study was to systematically review and critically appraise the evidence on the effectiveness of hypnosis for procedure-related pain and distress in pediatric cancer patients. A comprehensive search of major biomedical and specialist complementary and alternative medicine databases was conducted. Citations were included from the databases' inception to March 2005. Efforts were made to identify unpublished and ongoing research. Controlled trials were appraised using predefined criteria. Clinical commentaries were obtained for each study. Seven randomized controlled clinical trials and one controlled clinical trial were found. Studies report positive results, including statistically significant reductions in pain and anxiety/distress, but a number of methodological limitations were identified. Systematic searching and appraisal has demonstrated that hypnosis has potential as a clinically valuable intervention for procedure-related pain and distress in pediatric cancer patients. Further research into the effectiveness and acceptability of hypnosis for pediatric cancer patients is recommended.

Real-time, ultrasound-based control of a virtual hand by a trans-radial amputee.

PubMed

Baker, Clayton A; Akhlaghi, Nima; Rangwala, Huzefa; Kosecka, Jana; Sikdar, Siddhartha

2016-08-01

Advancements in multiarticulate upper-limb prosthetics have outpaced the development of intuitive, non-invasive control mechanisms for implementing them. Surface electromyography is currently the most popular non-invasive control method, but presents a number of drawbacks including poor deep-muscle specificity. Previous research established the viability of ultrasound imaging as an alternative means of decoding movement intent, and demonstrated the ability to distinguish between complex grasps in able-bodied subjects via imaging of the anterior forearm musculature. In order to translate this work to clinical viability, able-bodied testing is insufficient. Amputation-induced changes in muscular geometry, dynamics, and imaging characteristics are all likely to influence the effectiveness of our existing techniques. In this work, we conducted preliminary trials with a transradial amputee participant to assess these effects, and potentially elucidate necessary refinements to our approach. Two trials were performed, the first using a set of three motion types, and the second using four. After a brief training period in each trial, the participant was able to control a virtual prosthetic hand in real-time; attempted grasps were successfully classified with a rate of 77% in trial 1, and 71% in trial 2. While the results are sub-optimal compared to our previous able-bodied testing, they are a promising step forward. More importantly, the data collected during these trials can provide valuable information for refining our image processing methods, especially via comparison to previously acquired data from able-bodied individuals. Ultimately, further work with amputees is a necessity for translation towards clinical application.

Stroke prevention by cilostazol in patients with atherothrombosis: meta-analysis of placebo-controlled randomized trials.

PubMed

Uchiyama, Shinichiro; Demaerschalk, Bart M; Goto, Shinya; Shinohara, Yukito; Gotoh, Fumio; Stone, William M; Money, Samuel R; Kwon, Sun Uck

2009-01-01

Cilostazol is an antiplatelet agent that inhibits phosphodiesterase III in platelets and vascular endothelium. Previous randomized controlled trials of cilostazol for prevention of cerebrovascular events have garnered mixed results. We performed a systematic review and meta-analysis of the randomized clinical trials in patients with atherothrombotic diseases to determine the effects of cilostazol on cerebrovascular, cardiac, and all vascular events, and on all major hemorrhagic events. Relevant trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry for titles and abstracts. Data from 12 randomized controlled trials, involving 5674 patients, were analyzed for end points of cerebrovascular, cardiac, and major bleeding events. Searching, determination of eligibility, data extraction, and meta-analyses were conducted by multiple independent investigators. Data were available in 3782, 1187, and 705 patients with peripheral arterial disease, cerebrovascular disease, and coronary stenting, respectively. Incidence of total vascular events was significantly lower in the cilostazol group compared with the placebo group (relative risk [RR], 0.86; 95% confidence interval [CI], 0.74-0.99; P=.038). This was particularly influenced by a significant decrease of incidence of cerebrovascular events in the cilostazol group (RR, 0.58; 95% CI, 0.43-0.78; P < .001). There was no significant intergroup difference in incidence of cardiac events (RR, 0.99; 95% CI, 0.83-1.17; P=.908) and serious bleeding complications (RR, 1.00; 95% CI, 0.66-1.51; P=.996). This first meta-analysis of cilostazol in patients with atherothrombosis demonstrated a significant risk reduction for cerebrovascular events, with no associated increase of bleeding risk.

Experimental masseter muscle pain alters jaw-neck motor strategy.

PubMed

Wiesinger, B; Häggman-Henrikson, B; Hellström, F; Wänman, A

2013-08-01

A functional integration between the jaw and neck regions has been demonstrated during normal jaw function. The effect of masseter muscle pain on this integrated motor behaviour in man is unknown. The aim of this study was to investigate the effect of induced masseter muscle pain on jaw-neck movements during a continuous jaw opening-closing task. Sixteen healthy men performed continuous jaw opening-closing movements to a target position, defined as 75% of the maximum jaw opening. Each subject performed two trials without pain (controls) and two trials with masseter muscle pain, induced with hypertonic saline as a single injection. Simultaneous movements of the mandible and the head were registered with a wireless optoelectronic three-dimensional recording system. Differences in movement amplitudes between trials were analysed with Friedman's test and corrected Wilcoxon matched pairs test. The head movement amplitudes were significantly larger during masseter muscle pain trials compared with control. Jaw movement amplitudes did not differ significantly between any of the trials after corrected Wilcoxon tests. The ratio between head and jaw movement amplitudes was significantly larger during the first pain trial compared with control. Experimental masseter muscle pain in humans affected integrated jaw-neck movements by increasing the neck component during continuous jaw opening-closing tasks. The findings indicate that pain can alter the strategy for jaw-neck motor control, which further underlines the functional integration between the jaw and neck regions. This altered strategy may have consequences for development of musculoskeletal pain in the jaw and neck regions. © 2012 European Federation of International Association for the Study of Pain Chapters.

Flexible conflict management: conflict avoidance and conflict adjustment in reactive cognitive control.

PubMed

Dignath, David; Kiesel, Andrea; Eder, Andreas B

2015-07-01

Conflict processing is assumed to serve two crucial, yet distinct functions: Regarding task performance, control is adjusted to overcome the conflict. Regarding task choice, control is harnessed to bias decision making away from the source of conflict. Despite recent theoretical progress, until now two lines of research addressed these conflict-management strategies independently of each other. In this research, we used a voluntary task-switching paradigm in combination with response interference tasks to study both strategies in concert. In Experiment 1, participants chose between two univalent tasks on each trial. Switch rates increased following conflict trials, indicating avoidance of conflict. Furthermore, congruency effects in reaction times and error rates were reduced following conflict trials, demonstrating conflict adjustment. In Experiment 2, we used bivalent instead of univalent stimuli. Conflict adjustment in task performance was unaffected by this manipulation, but conflict avoidance was not observed. Instead, task switches were reduced after conflict trials. In Experiment 3, we used tasks comprising univalent or bivalent stimuli. Only tasks with univalent revealed conflict avoidance, whereas conflict adjustment was found for all tasks. On the basis of established theories of cognitive control, an integrative process model is described that can account for flexible conflict management. (c) 2015 APA, all rights reserved.

Animal-Assisted Therapy for Post-traumatic Stress Disorder: Lessons from "Case Reports" in Media Stories.

PubMed

Altschuler, Eric L

2018-01-01

Post-traumatic stress disorder (PTSD) can follow war trauma, sexual abuse, other traumas, and even be experienced by commanders for the PTSD of their subordinates. Medications and counseling are sometimes not effective, so new treatments are needed. Some years ago, I suggested that animal-assisted therapy (AAT) (pet therapy) might be beneficial for PTSD. A large randomized controlled trial is underway of canine-assisted therapy for PTSD. Randomized controlled trials are most useful in assessing the efficacy of a medical intervention as these trials control for known and unknown biases. However, due to their very nature and rigorous requirements, knowledge gained from randomized controlled trials may need to be supplemented from other kinds of studies. Here, I note that media reports of AAT for PTSD may effectively function as case reports and suggest further studies: For PTSD, these demonstrate that (1) AAT can be dramatically effective in improving PTSD symptoms; (2) there is the potential for benefit from AAT by multiple different animals besides canines for PTSD; and (3) AAT may have a role in preventing suicide in patients with PTSD. © Association of Military Surgeons of the United States 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Child language interventions in public health: a systematic literature review.

PubMed

De Cesaro, Bruna Campos; Gurgel, Léia Gonçalves; Nunes, Gabriela Pisoni Canedo; Reppold, Caroline Tozzi

2013-01-01

Systematically review the literature on interventions in children's language in primary health care. One searched the electronic databases (January 1980 to March 2013) MEDLINE (accessed by PubMed), Scopus, Lilacs and Scielo. The search terms used were "child language", "primary health care", "randomized controlled trial" and "intervention studies" (in English, Portuguese and Spanish). There were included any randomized controlled trials that addressed the issues child language and primary health care. The analysis was based on the type of language intervention conducted in primary health care. Seven studies were included and used intervention strategies such as interactive video, guidance for parents and group therapy. Individuals of both genders were included in the seven studies. The age of the children participant in the samples of the articles included in this review ranged from zero to 11 years. These seven studies used approaches that included only parents, parents and children or just children. The mainly intervention in language on primary health care, used in randomized controlled trials, involved the use of interactional video. Several professionals, beyond speech and language therapist, been inserted in the language interventions on primary health care, demonstrating the importance of interdisciplinary work. None of the articles mentioned aspects related to hearing. There was scarcity of randomized controlled trials that address on language and public health, either in Brazil or internationally.

A randomised controlled trial evaluating the utility of a patient Decision Aid to improve clinical trial (RAVES 08.03) related decision-making.

PubMed

Sundaresan, Puma; Ager, Brittany; Turner, Sandra; Costa, Dan; Kneebone, Andrew; Pearse, Maria; Woo, Henry; Tesson, Stephanie; Juraskova, Ilona; Butow, Phyllis

2017-10-01

Randomised controlled trials (RCTs) are considered the 'gold-standard' for evaluating medical treatments. However, patients and clinicians report difficulties with informed consent and recruitment. We evaluated the utility of a Decision Aid (DA) in reducing RCT-related decisional conflict, and improving RCT knowledge and recruitment. Potential participants for a radiotherapy RCT were invited to participate in the current study. Participants were randomised to receive the RCT's participant information sheet with or without a DA. Questionnaires were administered at baseline, one and six months. The primary outcome measure was decisional conflict. Secondary outcome measures included knowledge regarding and recruitment to the RCT. 129 men were randomised to the DA (63) and control (66) arms. Decisional conflict was significantly lower over 6-months (p=0.048) in the DA arm. Knowledge regarding the RCT was significantly higher at 6months (p=0.033) in the DA arm. 20.6% of the DA arm (13 of 63) and 9% of the control arm (6 of 66) entered the RCT. This study demonstrates the utility of a DA in reducing decisional conflict and improving trial knowledge in men with cancer who are making decisions regarding RCT participation. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Effects of Father-Neonate Skin-to-Skin Contact on Attachment: A Randomized Controlled Trial

PubMed Central

Chen, Er-Mei; Liu, Chieh-Yu

2017-01-01

This study examines how skin-to-skin contact between father and newborn affects the attachment relationship. A randomized controlled trial was conducted at a regional teaching hospital and a maternity clinic in northern Taiwan. The study recruited 83 first-time fathers aged 20 years or older. By block randomization, participants were allocated to an experimental (n = 41) or a control (n = 42) group. With the exception of skin-to-skin contact (SSC), participants from each group received the same standard care. Both groups also received an Early Childcare for Fathers nursing pamphlet. During the first three days postpartum, the intervention group members were provided a daily SSC intervention with their respective infants. Each intervention session lasted at least 15 minutes in length. The outcome measure was the Father-Child Attachment Scale (FCAS). After adjusting for demographic data, the changes to the mean FCAS were found to be significantly higher in the intervention group than in the control group. We recommend that nurses and midwives use instructional leaflets and demonstrations during postpartum hospitalization, encouraging new fathers to take an active role in caring for their newborn in order to enhance father-neonate interactions and establish parental confidence. This trial is registered with clinical trial registration number NCT02886767. PMID:28194281

Corticosteroids for the common cold.

PubMed

Hayward, Gail; Thompson, Matthew J; Perera, Rafael; Del Mar, Chris B; Glasziou, Paul P; Heneghan, Carl J

2015-10-13

The common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti-inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study. To compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults. We searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015). Randomised, double-blind, controlled trials comparing corticosteroids to placebo or to standard clinical management. Two review authors independently extracted data and assessed trial quality. We were unable to perform meta-analysis and instead present a narrative description of the available evidence. We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo-controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single-blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo-controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double-blind, placebo-controlled trials in adults and children are required to answer this question.

Comparing the effects of positive and negative feedback in information-integration category learning.

PubMed

Freedberg, Michael; Glass, Brian; Filoteo, J Vincent; Hazeltine, Eliot; Maddox, W Todd

2017-01-01

Categorical learning is dependent on feedback. Here, we compare how positive and negative feedback affect information-integration (II) category learning. Ashby and O'Brien (2007) demonstrated that both positive and negative feedback are required to solve II category problems when feedback was not guaranteed on each trial, and reported no differences between positive-only and negative-only feedback in terms of their effectiveness. We followed up on these findings and conducted 3 experiments in which participants completed 2,400 II categorization trials across three days under 1 of 3 conditions: positive feedback only (PFB), negative feedback only (NFB), or both types of feedback (CP; control partial). An adaptive algorithm controlled the amount of feedback given to each group so that feedback was nearly equated. Using different feedback control procedures, Experiments 1 and 2 demonstrated that participants in the NFB and CP group were able to engage II learning strategies, whereas the PFB group was not. Additionally, the NFB group was able to achieve significantly higher accuracy than the PFB group by Day 3. Experiment 3 revealed that these differences remained even when we equated the information received on feedback trials. Thus, negative feedback appears significantly more effective for learning II category structures. This suggests that the human implicit learning system may be capable of learning in the absence of positive feedback.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

PubMed Central

2012-01-01

Background Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. Methods/Design We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Discussion Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Trial registration Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18. PMID:22305183

Sub-Network Access Control Technology Demonstrator: Software Design of the Network Management System

DTIC Science & Technology

2002-08-01

Canadian Operational Fleet. Requirements The proposed network management solution must provide the normal monitoring and configuration mechanisms generally...Joint Warrior Inter- operability Demonstrations (JWID) m and the Communication System Network Inter- Operability (CSNI) Navy Network Trials. In short...management functional area normally includes two main functions: fault isolation and diagnosis, and restoration of the system . In short, an operator

Virtual Reality and Medical Inpatients: A Systematic Review of Randomized, Controlled Trials

PubMed Central

Dascal, Julieta; Reid, Mark; IsHak, Waguih William; Spiegel, Brennan; Recacho, Jennifer; Rosen, Bradley

2017-01-01

Objective: We evaluated the evidence supporting the use of virtual reality among patients in acute inpatient medical settings. Method: We conducted a systematic review of randomized controlled trials conducted that examined virtual reality applications in inpatient medical settings between 2005 and 2015. We used PsycINFO, PubMed, and Medline databases to identify studies using the keywords virtual reality, VR therapy, treatment, and inpatient. Results: We identified 2,024 citations, among which 11 met criteria for inclusion. Studies addressed three general areas: pain management, eating disorders, and cognitive and motor rehabilitation. Studies were small and heterogeneous and utilized different designs and measures. Virtual reality was generally well tolerated by patients, and a majority of studies demonstrated clinical efficacy. Studies varied in quality, as measured by an evaluation metric developed by Reisch, Tyson, and Mize (average quality score=0.87; range=0.78–0.96). Conclusion: Virtual reality is a promising intervention with several potential applications in the inpatient medical setting. Studies to date demonstrate some efficacy, but there is a need for larger, well-controlled studies to show clinical and cost-effectiveness. PMID:28386517

Virtual Reality and Medical Inpatients: A Systematic Review of Randomized, Controlled Trials.

PubMed

Dascal, Julieta; Reid, Mark; IsHak, Waguih William; Spiegel, Brennan; Recacho, Jennifer; Rosen, Bradley; Danovitch, Itai

2017-01-01

Objective: We evaluated the evidence supporting the use of virtual reality among patients in acute inpatient medical settings. Method: We conducted a systematic review of randomized controlled trials conducted that examined virtual reality applications in inpatient medical settings between 2005 and 2015. We used PsycINFO, PubMed, and Medline databases to identify studies using the keywords virtual reality , VR therapy , treatment , and inpatient. Results: We identified 2,024 citations, among which 11 met criteria for inclusion. Studies addressed three general areas: pain management, eating disorders, and cognitive and motor rehabilitation. Studies were small and heterogeneous and utilized different designs and measures. Virtual reality was generally well tolerated by patients, and a majority of studies demonstrated clinical efficacy. Studies varied in quality, as measured by an evaluation metric developed by Reisch, Tyson, and Mize (average quality score=0.87; range=0.78-0.96). Conclusion: Virtual reality is a promising intervention with several potential applications in the inpatient medical setting. Studies to date demonstrate some efficacy, but there is a need for larger, well-controlled studies to show clinical and cost-effectiveness.

Cognitive remediation for individuals with psychosis in a supported education setting: a randomized controlled trial.

PubMed

Kidd, Sean A; Kaur, Jaswant; Virdee, Gursharan; George, Tony P; McKenzie, Kwame; Herman, Yarissa

2014-08-01

Cognitive remediation (CR) has demonstrated good outcomes when paired with supported employment, however little is known about its effectiveness when integrated into a supported education program. This randomized controlled trial examined the effectiveness of integrating CR within a supported education program compared with supported education without CR. Thirty-seven students with psychosis were recruited into the study in the 2012 academic year. Academic functioning, cognition, self-esteem, and symptomatology were assessed at baseline, at 4months following the first academic term in which CR was provided, and at 8months assessing maintenance of gains. The treatment group demonstrated better retention in the academic program and a trend of improvement across a range of academic functional domains. While both treatment and control groups showed improvement in cognitive measures, the outcomes were not augmented by CR training. CR was also associated with significant and sustained improvements in self esteem. Further research, investigating specific intervention components is required to clarify the mixed findings regarding the effectiveness of CR in an education setting. Copyright © 2014 Elsevier B.V. All rights reserved.

Replication of a Prospective Randomized Controlled Trial of Resource Facilitation to Improve Return to Work and School After Brain Injury.

PubMed

Trexler, Lance E; Parrott, Devan R; Malec, James F

2016-02-01

To determine the extent to which previous findings on the effectiveness of resource facilitation to impact return to work and school could be replicated. Randomized controlled trial. Outpatient rehabilitation clinic. Outpatients with acquired brain injury (N=44). Fifteen months of resource facilitation services. A revised version of the Vocational Independence Scale and the Mayo-Portland Adaptability Inventory-4 Participation Index. Participants randomized to the resource facilitation group demonstrated a significant advantage in terms of rate and timing of return to productive community-based work relative to control participants. When examining only return to competitive work (and not return to school), 69% of the resource facilitation group was able to return compared with 50% of the control participants. Analyses of measures of participation in household and community activities revealed that both groups improved significantly over the 15-month study period, but no significant advantage for either group was demonstrated. This study replicates the positive impact of resource facilitation in improving productive community-based activity, including competitive employment and volunteering in the community. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Inter-trial alignment of EEG data and phase-locking

NASA Astrophysics Data System (ADS)

Testorf, M. E.; Horak, P.; Connolly, A.; Holmes, G. L.; Jobst, B. C.

2015-09-01

Neuro-scientific studies are often aimed at imaging brain activity, which is time-locked to external stimuli. This provides the possibility to use statistical methods to extract even weak signal components, which occur with each stimulus. For electroencephalographic recordings this concept is limited by inevitable time jitter, which cannot be controlled in all cases. Our study is based on a cross-correlation analysis of trials to alignment trials based on the recorded data. This is demonstrated both with simulated signals and with clinical EEG data, which were recorded intracranially. Special attention is given to the evaluation of the time-frequency resolved phase-locking across multiple trails.

Two parallel, pragmatic, UK multicentre, randomised controlled trials comparing surgical options for upper compartment (vault or uterine) pelvic organ prolapse (the VUE Study): study protocol for a randomised controlled trial.

PubMed

Glazener, Cathryn; Constable, Lynda; Hemming, Christine; Breeman, Suzanne; Elders, Andrew; Cooper, Kevin; Freeman, Robert; Smith, Anthony R B; Hagen, Suzanne; McDonald, Alison; McPherson, Gladys; Montgomery, Isobel; Kilonzo, Mary; Boyers, Dwayne; Goulao, Beatriz; Norrie, John

2016-09-08

One in three women who have a prolapse operation will go on to have another operation, though not necessarily in the same compartment. Surgery can result in greater impairment of quality of life than the original prolapse itself (such as the development of new-onset urinary incontinence, or prolapse at a different site). Anterior and posterior prolapse surgery is most common (90 % of operations), but around 43 % of women also have a uterine (34 %) or vault (9 %) procedure at the same time. There is not enough evidence from randomised controlled trials (RCTs) to guide management of vault or uterine prolapse. The Vault or Uterine prolapse surgery Evaluation (VUE) study aims to assess the surgical management of upper compartment pelvic organ prolapse (POP) in terms of clinical effectiveness, cost-effectiveness and adverse events. VUE is two parallel, pragmatic, UK multicentre, RCTs (Uterine Trial and Vault Trial). Eligible for inclusion are women with vault or uterine prolapse: requiring a surgical procedure, suitable for randomisation and willing to be randomised. Randomisation will be computer-allocated separately for each trial, minimised on: requiring concomitant anterior and/or posterior POP surgery or not, concomitant incontinence surgery or not, age (under 60 years or 60 years and older) and surgeon. Participants will be randomly assigned, with equal probability to intervention or control arms in either the Uterine Trial or the Vault Trial. Uterine Trial participants will receive either a vaginal hysterectomy or a uterine preservation procedure. Vault Trial participants will receive either a vaginal sacrospinous fixation or an abdominal sacrocolpopexy. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomisation) and also reviewed in clinic 12 months post surgery. The primary outcome is the participant-reported Pelvic Organ Prolapse Symptom Score (POP-SS) at 12 months post randomisation. Demonstrating the efficacy of vault and uterine prolapse surgeries is relevant not only to patients and clinicians but also to health care providers, both in the UK and globally. Current controlled trials ISRCTN86784244 (assigned 19 October 2012), and the first subject was randomly assigned on 1 May 2013.

The application of disease management to clinical trial designs.

PubMed

Puterman, Jared; Alter, David A

2009-08-01

The utilization of disease management (DM) as a minimum standard of care is believed to facilitate pronounced benefits in overall patient outcome and cost management. Randomized clinical trials remain the gold standard evaluative tool in clinical medicine. However, the extent to which contemporary cardiovascular clinical trials incorporate DM components into their treatment or control arms is unknown. Our study is the first to evaluate the extent to which clinical trials incorporate DM as a minimum standard of care for both the intervention and control groups. In total, 386 clinical trials published in 3 leading medical journals between 2003 and 2006 were evaluated. For each study, elements related to DM care, as defined using the American Heart Association Taxonomy, were abstracted and characterized. Our results demonstrate that while the application of DM has increased over time, only 3.4% of the clinical trials examined incorporated all 8 DM elements (and only 11% of such trials incorporated 4 DM elements). A significant association was found between study year and the inclusion of more than 3 elements of DM (chi(2) = 10.10 (3); p = 0.018). In addition, associations were found between study objective and DM criteria, as well as between cohort type and domains described. Our study serves as a baseline reference for the tracking of DM within, and its application to, randomized clinical trials. Moreover, our results underscore the need for broader implementation and evaluation of DM as a minimum care standard within clinical trial research.

Effectiveness of Xylitol in Reducing Dental Caries in Children.

PubMed

Marghalani, Abdullah A; Guinto, Emilie; Phan, Minhthu; Dhar, Vineet; Tinanoff, Norman

2017-03-15

The purpose of this study was to evaluate the effectiveness of xylitol in reducing dental caries in children compared to no treatment, a placebo, or preventive strategies. MEDLINE via PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from January 1, 1995 through Sept. 26, 2016 for randomized and controlled trials on children consuming xylitol for at least 12 months. The primary endpoint was caries reduction measured by mean decayed, missing, and filled primary and permanent surfaces/ teeth (dmfs/t, DMFS/T, respectively). The I2 and chi-square test for heterogeneity were used to detect trial heterogeneity. Meta-analyses were performed and quality was evaluated using GRADE profiler software. Analysis of five randomized controlled trials (RCTs) showed that xylitol had a small effect on reducing dental caries (standardized mean difference [SMD] equals -0.24; 95 percent confidence interval [CI] equals -0.48 to 0.01; P = 0.06) with a very low quality of evidence and considerable heterogeneity. Studies with higher xylitol doses (greater than four grams per day) demonstrated a medium caries reduction (SMD equals -0.54; 95 percent CI equals -1.14 to 0.05; P = 0.07), with these studies also having considerable heterogeneity and very low quality of evidence. The present systematic review examining the effectiveness of xylitol on caries incidence in children showed a small effect size in randomized controlled trials and a very low quality of evidence that makes preventive action of xylitol uncertain.

A Mixed-Methods, Randomized, Controlled Feasibility Trial to Inform the Design of a Phase III Trial to Test the Effect of the Handheld Fan on Physical Activity and Carer Anxiety in Patients With Refractory Breathlessness.

PubMed

Johnson, Miriam J; Booth, Sara; Currow, David C; Lam, Lawrence T; Phillips, Jane L

2016-05-01

The handheld fan is an inexpensive and safe way to provide facial airflow, which may reduce the sensation of chronic refractory breathlessness, a frequently encountered symptom. To test the feasibility of developing an adequately powered, multicenter, multinational randomized controlled trial comparing the efficacy of a handheld fan and exercise advice with advice alone in increasing activity in people with chronic refractory breathlessness from a variety of medical conditions, measuring recruitment rates; data quality; and potential primary outcome measures. This was a Phase II, multisite, international, parallel, nonblinded, mixed-methods randomized controlled trial. Participants were centrally randomized to fan or control. All received breathlessness self-management/exercise advice and were followed up weekly for four weeks. Participants/carers were invited to participate in a semistructured interview at the study's conclusion. Ninety-seven people were screened, 49 randomized (mean age 68 years; 49% men), and 43 completed the study. Site recruitment varied from 0.25 to 3.3/month and screening:randomization from 1.1:1 to 8.5:1. There were few missing data except for the Chronic Obstructive Pulmonary Disease Self-Efficacy Scale (two-thirds of data missing). No harms were observed. Three interview themes included 1) a fan is a helpful self-management strategy, 2) a fan aids recovery, and 3) a symptom control trial was welcome. A definitive, multisite trial to study the use of the handheld fan as part of self-management of chronic refractory breathlessness is feasible. Participants found the fan useful. However, the value of information for changing practice or policy is unlikely to justify the expense of such a trial, given perceived benefits, the minimal costs, and an absence of harms demonstrated in this study. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Evaluation of Electromyographic Biofeedback for the Quadriceps Femoris: A Systematic Review

PubMed Central

Wasielewski, Noah J.; Parker, Tonya M.; Kotsko, Kevin M.

2011-01-01

Objective: To critically review evidence for the effectiveness of electromyographic biofeedback (EMGB) of the quadriceps femoris muscle in treating various knee conditions. Data Sources: Databases used to locate randomized controlled trials included PubMed (1980–2010), Cumulative Index of Nursing and Allied Health Literature (CINAHL, 1995–2007), Web of Science (1986–2010), SPORTDiscus (1990–2007), and Physiotherapy Evidence Database (PEDro). Key words were knee and biofeedback. Study Selection: The criteria for selection were clinical randomized controlled trials in which EMGB of the quadriceps femoris was used for various knee conditions of musculoskeletal origin. Trials were excluded because of research designs other than randomized controlled trials, articles published in a non-English language, inclusion of healthy research participants, inability to identify EMGB as the source of clinical improvement, and lack of pain, functional outcome, or quadriceps torque as outcome measures. Data Extraction: Twenty specific data points were abstracted from each clinical trial under the broad categories of attributes of the patient and injury, treatment variables for the EMGB group, treatment variables for the control group, and attributes of the research design. Data Synthesis: Eight trials yielded a total of 319 participants with patellofemoral pain syndrome (n = 86), anterior cruciate ligament reconstruction (n = 52), arthroscopic surgery (n = 91), or osteoarthritis (n = 90). The average methodologic score of the included studies was 4.6/10 based on PEDro criteria. Pooled analyses demonstrated heterogeneity of the included studies, rendering the interpretation of the pooled data inappropriate. The EMGB appeared to benefit short-term postsurgical pain or quadriceps strength in 3 of 4 postsurgical investigations but was ineffective for chronic knee conditions such as patellofemoral pain and osteoarthritis in all 4 studies. Because the findings are based on limited data, caution is warranted until more randomized controlled trials are conducted to support or refute the general trends observed in this report. PMID:22488142

Environmental sanitary interventions for preventing active trachoma.

PubMed

Rabiu, M; Alhassan, M; Ejere, H

2005-04-18

Trachoma is the second or third major cause of blindness. It is responsible for about six million blind people worldwide, mostly in the poor communities of developing countries. One of the major strategies advocated for the control of the disease is the application of various environmental sanitary measures to such communities. To assess the evidence for the effectiveness of environmental sanitary measures on the prevalence of active trachoma in endemic areas. We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 4, 2004), MEDLINE (1966 to January 2005), EMBASE (1980 to January 2005), LILACS (April 2004), the reference list of trials and the Science Citation Index. We also contacted agencies, experts and researchers in trachoma control. This review included randomised and quasi-randomised controlled trials comparing any form of environmental hygiene measures with no measure. These hygienic measures included fly control, provision of water and health education. Participants in the trials were people normally resident in the trachoma endemic areas. Two authors independently extracted data and assessed the quality of trials. Study authors were contacted for additional information. Three trials met the inclusion criteria but meta-analysis was not conducted due to heterogeneity of the studies. Two studies that assessed insecticide spray as a fly control measure found that trachoma is reduced by at least 55% to 61% with this measure compared to no intervention. One study found that another fly control measure, latrine provision, reduced trachoma by 29.5% compared to no intervention; this was, however, not statistically significantly different. Another study revealed that health education on personal and household hygiene reduced the incidence of trachoma such that the odds of reducing trachoma in the health education village was about twice that of the no intervention village. However, all the studies have some methodological concerns relating to concealment of allocation and non-consideration of clustering effect in data analysis. There is evidence that insecticide spray as a fly control measure reduces trachoma significantly. Latrine provision as a fly control measure has not demonstrated significant trachoma reduction. Health education may be effective in reducing trachoma. There is a dearth of data to determine the effectiveness of all aspects of environmental sanitation in the control of trachoma.

Ethnography, fidelity, and the evidence that anthropology adds: supplementing the fidelity process in a clinical trial of supported employment.

PubMed

Smith-Morris, Carolyn; Lopez, Gilberto; Ottomanelli, Lisa; Goetz, Lance; Dixon-Lawson, Kimberly

2014-06-01

This discussion considers the role and findings of ethnographic research within a clinical trial of supported employment for veterans with spinal cord injury. Contributing to qualitative evaluation research and to debates over anthropological evidence vis-à-vis clinical trials, we demonstrate how enactors of a randomized controlled trial can simultaneously attend to both the trial's evidentiary and procedural requirements and to the lived experiences and needs of patients and clinicians. Three major findings are described: (1) contextual information essential to fidelity efforts within the trial; (2) the role of human interrelationships and idiosyncratic networks in the trial's success; and (3) a mapping of the power and authority structures relevant to the staff's ability to perform the protocol. We emphasize strengths of anthropological ethnography in clinical trials that include the provision of complementary, qualitative data, the capture of otherwise unmeasured parts of the trial, and the realization of important information for the translation of the clinical findings into new settings. © 2014 by the American Anthropological Association.

Comparison of a Stratified Group Intervention (STarT Back) With Usual Group Care in Patients With Low Back Pain: A Nonrandomized Controlled Trial.

PubMed

Murphy, Susan E; Blake, Catherine; Power, Camillus K; Fullen, Brona M

2016-04-01

A nonrandomized controlled trial. This study aims to explore the effectiveness of group-based stratified care in primary care. Stratified care based on psychosocial screening (STarT Back) has demonstrated greater clinical and cost-effectiveness in patients with low back pain. However, low back pain interventions are often delivered in groups and evaluating this system of care in a group setting is important. Patients were recruited from 60 general practices and linked physiotherapy services. A new group stratified intervention was compared with a historical nonstratified control group. Patients stratified as low, medium and high risk were offered risk-matched group care. Consenting participants completed self-report measures of functional disability (primary outcome measure), pain, psychological distress, and beliefs. The historical control received a generic group intervention. Analysis was by intention to treat. In total, 251 patients in the new stratified intervention and 332 in the historical control were included in the primary analysis at 12 weeks. The mean age of patients was 43 ± 10.98 years. Overall adjusted mean changes in the RMDQ scores were higher in the stratified intervention than in the control arm at 12-week follow-up (P = 0.028). Exploring the risk groups, individually the high-risk stratified group, demonstrated better outcome over the controls (P = 0.031). The medium-risk stratified intervention demonstrated equally good outcomes (P = 0.125), and low-risk stratified patients, despite less intervention, did as well as the historical controls (P = 0.993). Stratified care delivered in a group setting demonstrated superior outcomes in the high-risk patients, and equally good outcomes for the medium and low-risk groups. This model, embedded in primary care, provides an early and effective model of chronic disease management and adds another dimension to the utility of the STarT Back system of care. 2.

Cycling induced by electrical stimulation improves motor recovery in postacute hemiparetic patients: a randomized controlled trial.

PubMed

Ambrosini, Emilia; Ferrante, Simona; Pedrocchi, Alessandra; Ferrigno, Giancarlo; Molteni, Franco

2011-04-01

This study assessed whether cycling induced by functional electrical stimulation (FES) was more effective than passive cycling with placebo stimulation in promoting motor recovery and walking ability in postacute hemiparetic patients. In a double-blind, randomized, controlled trial, 35 patients were included and randomized to receive FES-induced cycling training or placebo FES cycling. The 4-week treatment consisted of 20 sessions lasting 25 minutes each. Primary outcome measures included the leg subscale of the Motricity Index and gait speed during a 50-meter walking test. Secondary outcomes were the Trunk Control Test, the Upright Motor Control Test, the mean work produced by the paretic leg, and the unbalance in mechanical work between paretic and nonparetic legs during voluntary pedaling. Participants were evaluated before training, after training, and at 3- to 5-month follow-up visits. No significant differences were found between groups at baseline. Repeated-measures ANOVA (P<0.05) revealed significant increases in Motricity Index, Trunk Control Test, Upright Motor Control Test, gait speed, and mean work of the paretic leg after training and at follow-up assessments for FES-treated patients. No outcome measures demonstrated significant improvements after training in the placebo group. Both groups showed no significant differences between assessments after training and at follow-up. A main effect favoring FES-treated patients was demonstrated by repeated-measures ANCOVA for Motricity Index (P<0.001), Trunk Control Test (P=0.001), Upright Motor Control Test (P=0.005), and pedaling unbalance (P=0.038). The study demonstrated that 20 sessions of FES cycling training significantly improved lower extremity motor functions and accelerated the recovery of overground locomotion in postacute hemiparetic patients. Improvements were maintained at follow-up.

Conflict adaptation in prefrontal cortex: now you see it, now you don't.

PubMed

Kim, Chobok; Johnson, Nathan F; Gold, Brian T

2014-01-01

Daily life requires people to monitor and resolve conflict arising from distracting information irrelevant to current goals. The highly influential conflict monitoring theory (CMT) holds that the anterior cingulate cortex (ACC) detects conflict and subsequently triggers the dorsolateral prefrontal cortex (DLPFC) to regulate that conflict. Multiple lines of evidence have provided support for CMT. For example, performance is faster on incongruent trials that follow other incongruent trials (iI), and is accompanied by reduced ACC and increased DLPFC activation (the conflict adaptation effect). In this fMRI study, we explored whether ACC-DLPFC conflict signaling can result in behavioral adjustments beyond on-line contexts. Participants completed a modified version of the Stroop conflict adaptation paradigm which tested for conflict adaptation effects on the current (N) trial associated with not only the immediately preceding (N - 1) trial, but also 2-back (N - 2) trials. Results demonstrated evidence for direct relationships between ACC activity on N - 2 trials and both N trial DLPFC activity and behavioral adjustment when intervening trials were congruent (i.e., icI). In contrast, when N - 1 trials were incongruent (i.e., iiI), ACC-DLPFC signaling failed and conflict adaptation was absent. These results provide new evidence demonstrating that the conflict monitor-controller maintains previously experienced conflict in the service of subsequent behavioral adjustment. However, the processing of multiple, temporally proximal conflict signals takes a toll on the working memory (WM) system, which appears to require resetting in order to adapt our behavior to frequently changing environmental demands. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Modern Magnetic Implant for Gastroesophageal Reflux Disease.

PubMed

Ganz, Robert A

2017-09-01

A magnetic implant for the treatment of gastroesophageal reflux disease (GERD) was Food and Drug Administration-approved in 2012 and has been extensively evaluated. The device is a ring of magnets that are placed around the gastroesophageal junction, augmenting the native lower esophageal sphincter and preventing reflux yet preserving lower esophageal sphincter physiologic function and allowing belching and vomiting. Magnetic force is advantageous, being permanent and precise, and forces between magnets decrease with esophageal displacement. Multiple patient cohorts have been studied using the magnetic device, and trials establish consistent, long-term improvement in pH data, GERD symptom scores, and proton-pump inhibitor use. A 5-year Food and Drug Administration trial demonstrated that most patients achieved normal pH scores, 85% stopped proton-pump inhibitors, and GERD health-related quality of life symptom scores improved from 27 to 4 at 5 years. Seven studies have compared magnetic augmentation with laparoscopic Nissen fundoplication and demonstrated that the magnetic device achieved comparable efficacy with regard to proton-pump inhibitor cessation, GERD symptom score improvement, and heartburn and regurgitation scores. However, to date there have been no randomized, controlled trials comparing the 2 techniques, and the study cohorts are not necessarily comparable regarding hiatal hernia size, severity of reflux, body mass index scores, or esophagitis scores. Dysphagia incidence was similar in both groups. Reoperation rates and safety profiles were also comparable, but the magnetic device demonstrated significant beneficial differences in allowing belching and vomiting. The magnetic device is safe, with the main adverse event being dysphagia with an approximate 3%-5% chronic incidence. Device removals in clinical trials have been between 0% and 7% and were uneventful. There have been no erosions, perforations, or infections in FDA clinical trials; erosions have rarely been noted in practice. Magnetic augmentation of the lower esophageal sphincter is a safe and effective operation for GERD, and should be considered a surgical option for those seeking a fundic-sparing operation, particularly those with parameters consistent with study cohorts. Additional randomized, controlled trials are underway. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Improving late life depression and cognitive control through the use of therapeutic video game technology: A proof-of-concept randomized trial.

PubMed

Anguera, Joaquin A; Gunning, Faith M; Areán, Patricia A

2017-06-01

Existing treatments for depression are known to have only modest effects, are insufficiently targeted, and are inconsistently utilized, particularly in older adults. Indeed, older adults with impaired cognitive control networks tend to demonstrate poor response to a majority of existing depression interventions. Cognitive control interventions delivered using entertainment software have the potential to not only target the underlying cerebral dysfunction associated with depression, but to do so in a manner that is engaging and engenders adherence to treatment protocol. In this proof-of-concept trial (Clinicaltrials.gov #: NCT02229188), individuals with late life depression (LLD) (22; 60+ years old) were randomized to either problem solving therapy (PST, n = 10) or a neurobiologically inspired digital platform designed to enhance cognitive control faculties (Project: EVO™, n = 12). Given the overlapping functional neuroanatomy of mood disturbances and executive dysfunction, we explored the impact of an intervention targeting cognitive control abilities, functional disability, and mood in older adults suffering from LLD, and how those outcomes compare to a therapeutic gold standard. EVO participants demonstrated similar improvements in mood and self-reported function after 4 weeks of treatment to PST participants. The EVO participants also showed generalization to untrained measures of working memory and attention, as well as negativity bias, a finding not evident in the PST condition. Individuals assigned to EVO demonstrated 100% adherence. This study provides preliminary findings that this therapeutic video game targeting cognitive control deficits may be an efficacious LLD intervention. Future research is needed to confirm these findings. © 2016 Wiley Periodicals, Inc.

Safe household water treatment and storage using ceramic drip filters: a randomised controlled trial in Bolivia.

PubMed

Clasen, T; Brown, J; Suntura, O; Collin, S

2004-01-01

A randomised controlled field trial was conducted to evaluate the effectiveness of ceramic drip filters to improve the microbiological quality of drinking water in a low-income community in rural Bolivia. In four rounds of water sampling over five months, 100% of the samples were free of thermotolerant (faecal) coliforms (TTC) compared to an arithmetic mean TTC count of 1517, 406, 167 and 245 among control households which continued to use their customary sources of drinking water. The filter systems produced water that consistently met WHO drinking-water standards despite levels of turbidity that presented a challenge to other low-cost POU treatment methods. The filter systems also demonstrated an ability to maintain the high quality of the treated water against subsequent re-contamination in the home.

Statins as antiarrhythmics: a systematic review part I: effects on risk of atrial fibrillation.

PubMed

Abuissa, Hussam; O'Keefe, James H; Bybee, Kevin A

2009-10-01

Recent studies have demonstrated that statins may possess antiarrhythmic properties in addition to their lipid-lowering effects. Studies which reported the association of statins with the incidence of atrial arrhythmias were identified through a systematic review of published literature. One randomized, placebo-controlled trial of 200 patients undergoing cardiac surgery showed that atorvastatin decreased the incidence of postoperative atrial fibrillation by 61%. Observational studies in patients with stable coronary disease, left ventricular dysfunction, or those undergoing cardiac or noncardiac surgery show that statin therapy is associated with an approximately 50% lower rate of atrial fibrillation. Two small randomized trials reported conflicting results: one showing that atorvastatin reduced the recurrence of AF after electrical cardioversion and the other finding that pravastatin did not. Published data suggests that statins may possess antiarrhythmic properties that reduce the propensity for atrial fibrillation. Most of this data is observational; more randomized, placebo-controlled trials are needed.

Effect of metronidazole versus standard care on length of stay of patients admitted with severe infectious mononucleosis: a randomized controlled trial.

PubMed

Lennon, P; O'Neill, J P; Fenton, J E

2014-07-01

Metronidazole may be of use in the treatment of infectious mononucleosis (IM). Our aim is to show that metronidazole shortens hospital stay for patients with severe IM. A single-centre randomized controlled trial was undertaken in patients admitted with severe IM, who were with a similar group treated by the standard care. Patients were blinded to which treatment arm they were in. Forty-two of these patients were enrolled in the trial. The primary endpoint was the difference in length of stay. This was significantly less in the metronidazole group (3.67 days v 4.67) (p 0.032). This study demonstrates that metronidazole has a role to play in severe infectious mononucleosis. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

PAHA study: Psychological Active and Healthy Aging: psychological wellbeing, proactive attitude and happiness effects of whole-body vibration versus Multicomponent Training in aged women: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Evidence demonstrates that physical exercise and psychological wellbeing are closely interlinked, particularly in older-aged women. However, research investigating how different forms of exercise influence mental health in older-aged women is underdeveloped. Methods/Design A randomized controlled trial (N = 300) will assess the relative effectiveness of two different exercise programs (whole-body vibration and Multicomponent Training) for improving psychological wellbeing in older-aged women. The following outcomes will be assessed at three time points (that is, pre, post, and follow-up): psychological wellbeing, proactive attitude, quality of life, and happiness. Discussion Results will have important implications for preventing psychological and physiological disease in older-aged women and for managing health-related costs for this population group. Trial registration Number NCT01966562 on Clinical Gov database the 8 October 2013 PMID:24886107

Topical Prophylaxis for HIV Prevention in Women: Becoming a Reality

PubMed Central

Verma, Natasha A.; Lee, Anna C.; Herold, Betsy C.

2011-01-01

Strategies to protect against sexual transmission of HIV include the development of products formulated for topical application, which limit the toxicities associated with systemic oral pre-exposure prophylaxis. Following several clinical trial failures, attention is now focused on antiretroviral (ARV) agents. Highly potent ARV topical formulations provide a female-controlled, targeted, and feasible option for HIV prevention. A recently completed tenofovir gel trial was the first to demonstrate significant protection against HIV acquisition. Topical ARVs have the advantage of delivering high concentration of drug at the site of transmission of HIV, with low systemic absorption. Sustained-release formulations, such as intravaginal rings, will likely improve adherence and can be designed to provide controlled and continuous delivery of ARV combinations. Further studies to test alternative dosing strategies and pharmacokinetic/pharmacodynamic relationships in the genital tract will provide valuable information as the field strives to improve upon the promising tenofovir gel trial results. PMID:21424725

The role of patent ductus arteriosus and its treatments in the development of bronchopulmonary dysplasia

PubMed Central

Clyman, Ronald I.

2013-01-01

A persistent left-to right shunt through a patent ductus arteriosus (PDA) increases the rate of hydrostatic fluid filtration into the lung’s interstitium, impairs pulmonary mechanics, and prolongs the need for mechanical ventilation. In preclinical trials, pharmacologic PDA closure leads to improved alveolarization and minimizes the impaired postnatal alveolar development that is the pathologic hallmark of the “new bronchopulmonary dysplasia (BPD)”. Although early pharmacologic closure of the PDA decreases the incidence of pulmonary hemorrhage, intraventricular hemorrhage, and the need for PDA ligation, there is little evidence from controlled, clinical trials to support or refute a causal role for the PDA in the development of BPD. On the other hand, evidence from epidemiologic, preclinical, and randomized controlled clinical trials demonstrate that early ductus ligation is an independent risk factor for the development of BPD and may directly contribute to the neonatal morbidities it is trying to prevent. PMID:23582964

Effect of protective filters on fire fighter respiratory health: field validation during prescribed burns.

PubMed

De Vos, Annemarie J B M; Cook, Angus; Devine, Brian; Thompson, Philip J; Weinstein, Philip

2009-01-01

Bushfire smoke contains a range of air toxics. To prevent inhalation of these toxics, fire fighters use respiratory equipment. Yet, little is known about the effectiveness of the equipment on the fire ground. Experimental trials in a smoke chamber demonstrated that, the particulate/organic vapor/formaldehyde (POVF) filter performed best under simulated conditions. This article reports on the field validation trials during prescribed burns in Western Australia. Sixty-seven career fire fighters from the Fire and Emergency Services Authority of Western Australia were allocated one of the three types of filters. Spirometry, oximetry, self-reported symptom, and personal air sampling data were collected before, during and after exposure to bushfire smoke from prescribed burns. Declines in FEV(1) and SaO(2) were demonstrated after 60 and 120 min exposure. A significant higher number of participants in the P filter group reported increases in respiratory symptoms after the exposure. Air sampling inside the respirators demonstrated formaldehyde levels significantly higher in the P filter group compared to the POV and the POVF filter group. The field validation trials during prescribed burns supported the findings from the controlled exposure trials in the smoke chamber. Testing the effectiveness of three types of different filters under bushfire smoke conditions in the field for up to 2 hr demonstrated that the P filter is ineffective in filtering out respiratory irritants. The performance of the POV and the POVF filter appears to be equally effective after 2 hr bushfire smoke exposure in the field.

Associations among comorbid anxiety, psychiatric symptomatology, and diabetic control in a population with serious mental illness and diabetes: Findings from an interventional randomized controlled trial.

PubMed

Aftab, Awais; Bhat, Chetan; Gunzler, Douglas; Cassidy, Kristin; Thomas, Charles; McCormick, Richard; Dawson, Neal V; Sajatovic, Martha

2018-05-01

Objective Serious mental illness and type II diabetes mellitus have a high comorbidity, and both have a higher prevalence of anxiety disorders compared to the general population. Targeted Training in Illness Management is a group-based self-management training approach which targets serious mental illness and type II diabetes mellitus concurrently. This analysis examines data from a randomized controlled trial of Targeted Training in Illness Management intervention to examine the impact of comorbid anxiety on baseline psychiatric symptomatology and diabetic control, and on longitudinal treatment outcomes. Methods We conducted secondary analyses on data from a prospective, 60-week, randomized controlled trial testing Targeted Training in Illness Management versus treatment as usual in 200 individuals with serious mental illness and diabetes. Primary outcomes included measures related to serious mental illness symptoms, functional status, general health status, and diabetes control. Measures were compared between those participants with anxiety disorders versus those without anxiety at baseline as well as over time using linear mixed effects analyses. Results Forty seven percent of the participants had one or more anxiety disorders. At baseline, those with an anxiety diagnosis had higher illness severity, depressive, and other psychiatric symptomatology and disability. Diabetic control (HbA1c) was not significantly different at baseline. In the longitudinal analyses, no significant mean slope differences over time (group-by-time interaction effect) between those with anxiety diagnoses and those without in treatment as usual group were found for primary outcomes. Within the Targeted Training in Illness Management arm, those with anxiety disorders had significantly greater improvement in mental health functioning. Those with anxiety comorbidity in the Targeted Training in Illness Management group demonstrated significantly lower HbA1c levels compared to no anxiety comorbidity and also demonstrated a greater improvement in HbA1c over the first 30 weeks compared to those without anxiety comorbidity. Conclusion Comorbid anxiety in serious mental illness and type II diabetes mellitus population is associated with increased psychiatric symptomatology and greater disability. Individuals from this population appear to experience greater improvement in functioning from baseline with the Targeted Training in Illness Management intervention. Anxiety comorbidity in the serious mental illness and type II diabetes mellitus population does not appear to have a negative impact on diabetic control. These complex relationships need further study. Clinical Trials Registration ClinicalTrials.gov: Improving outcomes for individuals with serious mental illness and diabetes (NCT01410357).

The CEA Second-Look Trial: a randomised controlled trial of carcinoembryonic antigen prompted reoperation for recurrent colorectal cancer

PubMed Central

Treasure, Tom; Monson, Kathryn; Fiorentino, Francesca; Russell, Christopher

2014-01-01

Objective In patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit? Design A randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative. Setting 58 hospitals in the UK. Participants From 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms. Interventions ‘Second-look’ surgery with intention to remove any recurrence discovered. Primary outcome measure Survival. Results By February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival. Conclusions The trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years. Trial registration number ISRCTN76694943. PMID:24823671

Effects of preparation time and trial type probability on performance of anti- and pro-saccades.

PubMed

Pierce, Jordan E; McDowell, Jennifer E

2016-02-01

Cognitive control optimizes responses to relevant task conditions by balancing bottom-up stimulus processing with top-down goal pursuit. It can be investigated using the ocular motor system by contrasting basic prosaccades (look toward a stimulus) with complex antisaccades (look away from a stimulus). Furthermore, the amount of time allotted between trials, the need to switch task sets, and the time allowed to prepare for an upcoming saccade all impact performance. In this study the relative probabilities of anti- and pro-saccades were manipulated across five blocks of interleaved trials, while the inter-trial interval and trial type cue duration were varied across subjects. Results indicated that inter-trial interval had no significant effect on error rates or reaction times (RTs), while a shorter trial type cue led to more antisaccade errors and faster overall RTs. Responses following a shorter cue duration also showed a stronger effect of trial type probability, with more antisaccade errors in blocks with a low antisaccade probability and slower RTs for each saccade task when its trial type was unlikely. A longer cue duration yielded fewer errors and slower RTs, with a larger switch cost for errors compared to a short cue duration. Findings demonstrated that when the trial type cue duration was shorter, visual motor responsiveness was faster and subjects relied upon the implicit trial probability context to improve performance. When the cue duration was longer, increased fixation-related activity may have delayed saccade motor preparation and slowed responses, guiding subjects to respond in a controlled manner regardless of trial type probability. Copyright © 2016 Elsevier B.V. All rights reserved.

Synergistic effect of acupuncture and mirror therapy on post-stroke upper limb dysfunction: a study protocol for a randomized controlled trial.

PubMed

Xu, Ying; Lin, Shufang; Jiang, Cai; Ye, Xiaoqian; Tao, Jing; Wilfried, Schupp; Wong, Alex W K; Chen, Lidian; Yang, Shanli

2018-05-31

Upper limb dysfunction is common after stroke, posing an important challenge for post-stroke rehabilitation. The clinical efficacy of acupuncture for the recovery of post-stroke upper limb function has been previously demonstrated. Mirror therapy (MT) has also been found to be effective. However, the effects of acupuncture and MT have not been systematically compared. This trial aims to elucidate the synergistic effects of acupuncture and MT on upper limb dysfunction after stroke. A 2 × 2 factorial randomized controlled trial will be conducted at the rehabilitation hospitals affiliated with Fujian University of Traditional Chinese Medicine. A total of 136 eligible subjects will be randomly divided into acupuncture treatment (AT), MT, combined treatment, and control groups in a 1:1:1:1 ratio. All subjects will receive conventional treatment. The interventions will be performed 5 days per week for 4 weeks. AT, MT, and combined treatment will be performed for 30 min per day (combined treatment: AT 15 min + MT 15 min). The primary outcomes in this study will be the mean change in scores on both the FMA and WMFT from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The secondary outcomes are the mean change in the scores on the Visual Analogue Scale, Stroke Impact Scale, and modified Barthel index. Medical abstraction of adverse events will be assessed at each visit. The results of this trial will demonstrate the synergistic effect of acupuncture and MT on upper limb motor dysfunction after stroke. In addition, whether AT and MT, either combined or alone, are more effective than the conventional treatment in the management of post-stroke upper limb dysfunction will also be determined. Chinese Clinical Trial Registry: ChiCTR-IOR-17011118 . Registered on April 11, 2017. Version number: 01.2016.09.1.

Adverse effects of homeopathy, what do we know? A systematic review and meta-analysis of randomized controlled trials.

PubMed

Stub, Trine; Musial, Frauke; Kristoffersen, Agnete A; Alræk, Terje; Liu, Jianping

2016-06-01

Homeopathy is a popular treatment modality among patient, however there is sparse research about adverse effects of homeopathy. A concept unique for homeopathy, is homeopathic aggravation that is understood as a transient worsening of the patients' symptoms before an expected improvement occurs. From a risk perspective it is vital that a distinction between homeopathic aggravations and adverse effects is established. There is a lack of systematic information on how frequent adverse effects and homeopathic aggravations are reported in studies. Therefore, a systematic review and meta-analysis were performed. Sixteen electronic databases were searched for Randomized Controlled Trials (RCTs). The searches were limited from the year 1995 to January 2011. Forty-one RCTs, with a total of 6.055 participants were included. A subtotal of 39 studies was included in the additional meta-analysis. A total of 28 trials (68%) reported adverse effects and five trials (12%) reported homeopathic aggravations. The meta-analysis (including six subgroup comparisons) demonstrated that no significant difference was found between homeopathy and control with OR 0.99, 95% CI 0.86-1.14, I(2)=54%. More than two third of the adverse effects were classified as grade 1 (68%) and two third were classified as grade 2 (25%) and grade 3 (6%) according to the Common Terminology Criteria for Adverse Effects. Homeopathic aggravation was classified as grade 1 (98%) and grade 3 (2%), suggesting that homeopathic aggravations were reported to be less severe than adverse effects. The methodological quality according to a method recommended in the Cochrane handbook for RCTs, was high. Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta-analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development and Evaluation of a Pedagogical Tool to Improve Understanding of a Quality Checklist: A Randomised Controlled Trial

PubMed Central

Fourcade, Lola; Boutron, Isabelle; Moher, David; Ronceray, Lucie; Baron, Gabriel; Ravaud, Philippe

2007-01-01

Objective: The aim of this study was to develop and evaluate a pedagogical tool to enhance the understanding of a checklist that evaluates reports of nonpharmacological trials (CLEAR NPT). Design: Paired randomised controlled trial. Participants: Clinicians and systematic reviewers. Interventions: We developed an Internet-based computer learning system (ICLS). This pedagogical tool used many examples from published randomised controlled trials to demonstrate the main coding difficulties encountered when using this checklist. Randomised participants received either a specific Web-based training with the ICLS (intervention group) or no specific training. Outcome measures: The primary outcome was the rate of correct answers compared to a criterion standard for coding a report of randomised controlled trials with the CLEAR NPT. Results: Between April and June 2006, 78 participants were randomly assigned to receive training with the ICLS (39) or no training (39). Participants trained by the ICLS did not differ from the control group in performance on the CLEAR NPT. The mean paired difference and corresponding 95% confidence interval was 0.5 (−5.1 to 6.1). The rate of correct answers did not differ between the two groups regardless of the CLEAR NPT item. Combining both groups, the rate of correct answers was high or items related to allocation sequence (79.5%), description of the intervention (82.0%), blinding of patients (79.5%), and follow-up schedule (83.3%). The rate of correct answers was low for items related to allocation concealment (46.1%), co-interventions (30.3%), blinding of outcome assessors (53.8%), specific measures to avoid ascertainment bias (28.6%), and intention-to-treat analysis (60.2%). Conclusions: Although we showed no difference in effect between the intervention and control groups, our results highlight the gap in knowledge and urgency for education on important aspects of trial conduct. PMID:17479163

Breaking bad habits by improving executive function in individuals with obesity.

PubMed

Allom, Vanessa; Mullan, Barbara; Smith, Evelyn; Hay, Phillipa; Raman, Jayanthi

2018-04-16

Two primary factors that contribute to obesity are unhealthy eating and sedentary behavior. These behaviors are particularly difficult to change in the long-term because they are often enacted habitually. Cognitive Remediation Therapy has been modified and applied to the treatment of obesity (CRT-O) with preliminary results of a randomized controlled trial demonstrating significant weight loss and improvements in executive function. The objective of this study was to conduct a secondary data analysis of the CRT-O trial to evaluate whether CRT-O reduces unhealthy habits that contribute to obesity via improvements in executive function. Eighty participants with obesity were randomized to CRT-O or control. Measures of executive function (Wisconsin Card Sort Task and Trail Making Task) and unhealthy eating and sedentary behavior habits were administered at baseline, post-intervention and at 3 month follow-up. Participants receiving CRT-O demonstrated improvements in both measures of executive function and reductions in both unhealthy habit outcomes compared to control. Mediation analyses revealed that change in one element of executive function performance (Wisconsin Card Sort Task perseverance errors) mediated the effect of CRT-O on changes in both habit outcomes. These results suggest that the effectiveness of CRT-O may result from the disruption of unhealthy habits made possible by improvements in executive function. In particular, it appears that cognitive flexibility, as measured by the Wisconsin Card Sort task, is a key mechanism in this process. Improving cognitive flexibility may enable individuals to capitalise on interruptions in unhealthy habits by adjusting their behavior in line with their weight loss goals rather than persisting with an unhealthy choice. The RCT was registered with the Australian New Zealand Registry of Clinical Trials (trial id: ACTRN12613000537752 ).

A Randomized Controlled Trial of Atorvastatin in Patients With Bronchiectasis Infected With Pseudomonas Aeruginosa: A Proof of Concept Study.

PubMed

Bedi, Pallavi; Chalmers, James D; Graham, Catriona; Clarke, Andrea; Donaldson, Samantha; Doherty, Catherine; Govan, John R W; Davidson, Donald J; Rossi, Adriano G; Hill, Adam T

2017-08-01

There are no randomized controlled trials of statin therapy in patients with severe bronchiectasis who are chronically infected with Pseudomonas aeruginosa. Thirty-two patients chronically infected with P aeruginosa were recruited in this double-blind cross-over randomized controlled trial. Sixteen patients were recruited in each arm, were given atorvastatin 80 mg or placebo for 3 months followed by a washout period for 6 weeks, and then crossed over and administered the alternative therapy for 3 months. Twenty-seven patients completed the study. Atorvastatin did not significantly improve the primary end point of cough as measured by the Leicester Cough Questionnaire (mean difference, 1.92; 95% CI for difference, -0.57-4.41; P = .12). However, atorvastatin treatment resulted in an improved St. Georges Respiratory Questionnaire (-5.62 points; P = .016) and reduced serum levels of CXCL8 (P = .04), tumor necrosis factor (P = .01), and intercellular adhesion molecule 1 (P = .04). There was a trend toward improvement in serum C-reactive protein and serum neutrophil counts (P = .07 and P = .06, respectively). We demonstrated in vitro that atorvastatin 10 μM reduced formyl-methionyl-leucyl phenylalanine-induced upregulation of CD11b expression and changes in calcium flux, reflecting an ability to decrease neutrophil activation. We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in patients with bronchiectasis who were infected with P aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation. ClinicalTrials.gov; No.: NCT01299194; URL: www.clinicaltrials.gov. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of mirror therapy on walking ability, balance and lower limb motor recovery after stroke: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Li, Yi; Wei, Qingchuan; Gou, Wei; He, Chengqi

2018-04-01

To investigate the effects of mirror therapy on walking ability, balance and lower limb motor recovery in patients with stroke. MEDLINE, EMBASE, Web of Science, CENTRAL, PEDro Database, CNKI, VIP, Wan Fang, ClinicalTrials.gov, Current controlled trials and Open Grey were searched for randomized controlled trials that investigated the effects of mirror therapy on lower limb function through January 2018. The primary outcomes included were walking speed, mobility and balance function. Secondary outcomes included lower limb motor recovery, spasticity and range of motion. Quality assessments were performed with the PEDro scale. A total of 13 studies ( n = 572) met the inclusion criteria. A meta-analysis demonstrated a significant effect of mirror therapy on walking speed (mean difference (MD) 0.1 m/s, 95% confidence interval (CI): 0.08 to 0.12, P < 0.00001), balance function (standard mean difference (SMD) 0.66, 95% CI: 0.43 to 0.88, P < 0.00001), lower limb motor recovery (SMD 0.83, 95% CI: 0.62 to 1.05, P < 0.00001) and passive range of motion of ankle dorsiflexion (MD 2.07°, 95% CI: 082 to 3.32, P = 0.001), without improving mobility (SMD 0.43, 95% CI: -0.12 to 0.98, P = 0.12) or spasticity of ankle muscles (MD -0.14, 95% CI: -0.43 to 0.15, P = 0.35). The systematic review demonstrates that the use of mirror therapy in addition to some form of rehabilitation appears promising for some areas of lower limb function, but there is not enough evidence yet to suggest when and how to approach this therapy.

Impacts of Social-Emotional Curricula on Three-Year-Olds: Exploratory Findings from the Head Start CARES Demonstration. Research Snapshot. OPRE Report 2014-78

ERIC Educational Resources Information Center

Hsueh, JoAnn; Lowenstein, Amy E.; Morris, Pamela; Mattera, Shira K.; Bangser, Michael

2014-01-01

This report presents exploratory impact findings for 3-year-olds from the Head Start CARES demonstration, a large-scale randomized controlled trial implemented in Head Start centers for one academic year across the country. The study was designed primarily to test the effects of the enhancements on 4-year-olds, but it also provides an opportunity…

Estimating mean QALYs in trial-based cost-effectiveness analysis: the importance of controlling for baseline utility.

PubMed

Manca, Andrea; Hawkins, Neil; Sculpher, Mark J

2005-05-01

In trial-based cost-effectiveness analysis baseline mean utility values are invariably imbalanced between treatment arms. A patient's baseline utility is likely to be highly correlated with their quality-adjusted life-years (QALYs) over the follow-up period, not least because it typically contributes to the QALY calculation. Therefore, imbalance in baseline utility needs to be accounted for in the estimation of mean differential QALYs, and failure to control for this imbalance can result in a misleading incremental cost-effectiveness ratio. This paper discusses the approaches that have been used in the cost-effectiveness literature to estimate absolute and differential mean QALYs alongside randomised trials, and illustrates the implications of baseline mean utility imbalance for QALY calculation. Using data from a recently conducted trial-based cost-effectiveness study and a micro-simulation exercise, the relative performance of alternative estimators is compared, showing that widely used methods to calculate differential QALYs provide incorrect results in the presence of baseline mean utility imbalance regardless of whether these differences are formally statistically significant. It is demonstrated that multiple regression methods can be usefully applied to generate appropriate estimates of differential mean QALYs and an associated measure of sampling variability, while controlling for differences in baseline mean utility between treatment arms in the trial. Copyright 2004 John Wiley & Sons, Ltd

Registration status and methodological reporting of randomized controlled trials in obesity research: A review.

PubMed

Byrne, Jillian L S; Yee, Tamara; O'Connor, Kathleen; Dyson, Michele P; Ball, Geoff D C

2017-04-01

To assess registration and reporting details of randomized controlled trials (RCTs) published from 2011 to 2016 across four obesity journals. All issues from four leading obesity journals were searched systematically for RCTs from January 2011 to June 2016. Data on registration status were extracted from manuscripts, online trial registries, and a trial database; corresponding authors were contacted for registration details, when necessary. The methodological reporting of RCTs was assessed on specific criteria from the Consolidated Standards of Reporting Trials. A total of 223 RCTs were reviewed. Three-quarters (n = 170) were registered publicly; 94 (55.3%) reported registration details in the manuscript, and 82 (48.2%) were registered prospectively. Newer RCTs were more likely to be registered prospectively than older RCTs (2014-2016: 57.3% vs. 2011-2013: 39.2%; c 2  = 5.5, P = 0.02). Assessment on the Consolidated Standards of Reporting Trials demonstrated that less than half of all studies reported data collection dates (n = 108; 48.4%) or included "randomized trial" in the title (n = 89; 39.9%). The methodological reporting of RCTs published in obesity journals is suboptimal, despite current guidelines and policies. To complement existing standards, editorial boards should incorporate mandatory fields within the online manuscript submission process to enhance the quality, transparency, and comprehensiveness of reporting RCTs in obesity journals. © 2017 The Obesity Society.

Testing the Replicability of a Successful Care Management Program: Results from a Randomized Trial and Likely Explanations for Why Impacts Did Not Replicate.

PubMed

Peterson, G Greg; Zurovac, Jelena; Brown, Randall S; Coburn, Kenneth D; Markovich, Patricia A; Marcantonio, Sherry A; Clark, William D; Mutti, Anne; Stepanczuk, Cara

2016-12-01

To test whether a care management program could replicate its success in an earlier trial and determine likely explanations for why it did not. Medicare claims and nurse contact data for Medicare fee-for-service beneficiaries with chronic illnesses enrolled in the trial in eastern Pennsylvania (N = 483). A randomized trial with half of enrollees receiving intensive care management services and half receiving usual care. We developed and tested hypotheses for why impacts declined. All outcomes and covariates were derived from claims and the nurse contact data. From 2010 to 2014, the program did not reduce hospitalizations or generate Medicare savings to offset program fees that averaged $260 per beneficiary per month. These estimates are statistically different (p < .05) from the large reductions in hospitalizations and spending in the first trial (2002-2010). The treatment-control differences in the second trial disappeared because the control group's risk-adjusted hospitalization rate improved, not because the treatment group's outcomes worsened. Even if demonstrated in a randomized trial, successful results from one test may not replicate in other settings or time periods. Assessing whether gaps in care that the original program filled exist in other settings can help identify where earlier success is likely to replicate. © Health Research and Educational Trust.

Recommendations for the clinical evaluation of agents for treatment of osteoporosis: consensus of an expert panel representing the American Society for Bone and Mineral Research (ASBMR), the International Society for Clinical Densitometry (ISCD), and the National Osteoporosis Foundation (NOF).

PubMed

Silverman, Stuart L; Cummings, Steven R; Watts, Nelson B

2008-01-01

A panel of experts representing ASBMR, NOF, and ISCD reviewed evidence and reached consensus that regulatory approval of treatments for osteoporosis should be based on trials with fracture endpoints, lasting 18-24 mo, and extending treatment to 5 yr; other indications could be approved based on BMD and turnover markers. In response to an FDA request for clinical trial guidance in osteoporosis, an expert panel was convened with representatives from the American Society of Bone and Mineral Research, the International Society of Clinical Densitometry, and the National Osteoporosis Foundation. The panel used a validated evidence-based expert panel process (the Rand Appropriateness Method) to address issues of trial duration, trial design, use of intermediate endpoints as outcomes, and use of placebo-controlled trials in high-risk patients. The panel concluded that placebo-controlled trials with fracture endpoints are appropriate and, with informed consent, are ethical for registration of new compounds. Trials may be 18-24 mo in duration for efficacy, assuming longer duration to 5 yr for safety and demonstration of sustained fracture reduction. Once fracture efficacy has been established for a particular agent, intermediate endpoints (e.g., BMD and bone turnover markers) may be used as outcomes for new indications other than corticosteroid-induced osteoporosis.

Probing the nature of deficits in the 'Approximate Number System' in children with persistent Developmental Dyscalculia.

PubMed

Bugden, Stephanie; Ansari, Daniel

2016-09-01

In the present study we examined whether children with Developmental Dyscalculia (DD) exhibit a deficit in the so-called 'Approximate Number System' (ANS). To do so, we examined a group of elementary school children who demonstrated persistent low math achievement over 4 years and compared them to typically developing (TD), aged-matched controls. The integrity of the ANS was measured using the Panamath (www.panamath.org) non-symbolic numerical discrimination test. Children with DD demonstrated imprecise ANS acuity indexed by larger Weber fraction (w) compared to TD controls. Given recent findings showing that non-symbolic numerical discrimination is affected by visual parameters, we went further and investigated whether children performed differently on trials on which number of dots and their overall area were either congruent or incongruent with each other. This analysis revealed that differences in w were only found between DD and TD children on the incongruent trials. In addition, visuo-spatial working memory strongly predicts individual differences in ANS acuity (w) during the incongruent trials. Thus the purported ANS deficit in DD can be explained by a difficulty in extracting number from an array of dots when area is anti-correlated with number. These data highlight the role of visuo-spatial working memory during the extraction process, and demonstrate that close attention needs to be paid to perceptual processes invoked by tasks thought to represent measures of the ANS. © 2015 John Wiley & Sons Ltd.

Evidence of Pavlovian conditioned fear following electrical stimulation of the periaqueductal grey in the rat.

PubMed

Di Scala, G; Mana, M J; Jacobs, W J; Phillips, A G

1987-01-01

Stimulation of the periaqueductal grey (PAG) has been used to support aversive conditioning in a variety of species with several experimental paradigms. However, it has not been clearly demonstrated whether the behavioral changes produced by PAG stimulation in these paradigms are mediated by associative or nonassociative mechanisms. The present studies demonstrate that electrical stimulation of the PAG in the rat may be used to support associative learning in a Pavlovian paradigm. In each experiment, a fully controlled conditional emotional response (CER) procedure was used to examine the unconditional aversive properties of PAG stimulation. In Experiment 1a, weak associative conditioning was observed when a light CS was paired with PAG stimulation over 6 conditioning trials. In Experiment 1b, robust associative conditioning was obtained with a light CS when 18 conditioning trials were used. In Experiment 2, robust associative conditioning was demonstrated with a tone CS when 6 conditioning trials were used. The results parallel those found when other aversive stimuli are used as a UCS (e.g., footshock or intraorbital air puff), and because the present experiments included the proper control procedures the results clearly indicate that the behavioral changes produced by PAG stimulation are mediated by associative Pavlovian learning mechanisms rather than nonassociative mechanisms such as sensitization or pseudoconditioning. The present technique may be useful for assessing the neuroanatomical and neurochemical substrates underlying the aversive effects of brain-stimulation, and for screening the effects of drugs on the conditional and unconditional responses produced by such stimulation.

The process of developing and implementing a telephone-based peer support program for postpartum depression: evidence from two randomized controlled trials

PubMed Central

2014-01-01

Background A randomized controlled trial evaluated the effect of telephone-based peer support on preventing postpartum depression (PPD) among high-risk mothers. The results indicated that support provided by peer volunteers may be an effective preventative strategy. The purpose of this paper is to outline the process of developing, implementing, maintaining, and evaluating the peer support program that we used in this PPD prevention trial. Methods The peer support program had been used successfully in a pilot trial and a previous breastfeeding peer support trial. Based on our experience and lessons learned, we developed a 4-phase, 12-step approach so that the peer support model could be copied and used by different health providers in various settings. We will use the PPD prevention trial to demonstrate the suggested steps. Results The trial aim to prevent the onset of PPD was established. Peer volunteers who previously experienced and recovered from self-reported PPD were recruited and attended a four-hour training session. Volunteers were screened and those identified as appropriate to provide support to postpartum mothers were selected. Women who scored more than 9 on the Edinburgh Postnatal Depression Scale within the first two weeks after childbirth were recruited to participate in the trial and proactive, individualized, telephone-based peer support (mother-to-mother) was provided to those randomized to the intervention group. Peer volunteers maintained the intervention, supported other volunteers, and evaluated the telephone-based support program. Possible negative effects of the intervention were assessed. An in-depth assessment of maternal perspectives of the program at 12 weeks postpartum was performed. Conclusions The 4-phase, 12-step approach delineated in this paper provides clear and concise guidelines for health professionals to follow in creating and implementing community-based, peer-support interventions with the potential to prevent PPD. Trial registration Current Controlled Trials ISRCTN68337727. PMID:24742217

Atrial fibrillation and stroke: the evolving role of rhythm control.

PubMed

Patel, Taral K; Passman, Rod S

2013-06-01

Atrial fibrillation (AF) remains a major risk factor for stroke. Unfortunately, clinical trials have failed to demonstrate that a strategy of rhythm control--therapy to maintain normal sinus rhythm (NSR)--reduces stroke risk. The apparent lack of benefit of rhythm control likely reflects the difficulty in maintaining NSR using currently available therapies. However, there are signals from several trials that the presence of NSR is indeed beneficial and associated with better outcomes related to stroke and mortality. Most electrophysiologists feel that as rhythm control strategies continue to improve, the crucial link between rhythm control and stroke reduction will finally be demonstrated. Therefore, AF specialists tend to be aggressive in their attempts to maintain NSR, especially in patients who have symptomatic AF. A step-wise approach from antiarrhythmic drugs to catheter ablation to cardiac surgery is generally used. In select patients, catheter ablation or cardiac surgery may supersede antiarrhythmic drugs. The choice depends on the type of AF, concurrent heart disease, drug toxicity profiles, procedural risks, and patient preferences. Regardless of strategy, given the limited effectiveness of currently available rhythm control therapies, oral anticoagulation is still recommended for stroke prophylaxis in AF patients with other stroke risk factors. Major challenges in atrial fibrillation management include selecting patients most likely to benefit from rhythm control, choosing specific antiarrhythmic drugs or procedures to achieve rhythm control, long-term monitoring to gauge the efficacy of rhythm control, and determining which (if any) patients may safely discontinue anticoagulation if long-term NSR is achieved.

Simple Psychological Interventions for Reducing Pain From Common Needle Procedures in Adults

PubMed Central

Boerner, Katelynn E.; Birnie, Kathryn A.; Taddio, Anna; McMurtry, C. Meghan; Noel, Melanie; Shah, Vibhuti; Pillai Riddell, Rebecca

2015-01-01

Background: This systematic review evaluated the effectiveness of simple psychological interventions for managing pain and fear in adults undergoing vaccination or related common needle procedures (ie, venipuncture/venous cannulation). Design/Methods: Databases were searched to identify relevant randomized and quasi-randomized controlled trials. Self-reported pain and fear were prioritized as critically important outcomes. Data were combined using standardized mean difference (SMD) or relative risk (RR) with 95% confidence intervals (CI). Results: No studies involving vaccination met inclusion criteria; evidence was drawn from 8 studies of other common needle procedures (eg, venous cannulation, venipuncture) in adults. Two trials evaluating the impact of neutral signaling of the impending procedure (eg, “ready?”) as compared with signaling of impending pain (eg, “sharp scratch”) demonstrated lower pain when signaled about the procedure (n=199): SMD=−0.97 (95% CI, −1.26, −0.68), after removal of 1 trial where self-reported pain was significantly lower than the other 2 included trials. Two trials evaluated music distraction (n=156) and demonstrated no difference in pain: SMD=0.10 (95% CI, −0.48, 0.27), or fear: SMD=−0.25 (95% CI, −0.61, 0.10). Two trials evaluated visual distraction and demonstrated no difference in pain (n=177): SMD=−0.57 (95% CI, −1.82, 0.68), or fear (n=81): SMD=−0.05 (95% CI, −0.50, 0.40). Two trials evaluating breathing interventions found less pain in intervention groups (n=138): SMD=−0.82 (95% CI, −1.21, −0.43). The quality of evidence across all trials was very low. Conclusions: There are no published studies of simple psychological interventions for vaccination pain in adults. There is some evidence of a benefit from other needle procedures for breathing strategies and neutral signaling of the start of the procedure. There is no evidence for use of music or visual distraction. PMID:26352921

The influence of an audience response system on knowledge retention: an application to resident education.

PubMed

Pradhan, Archana; Sparano, Dina; Ananth, Cande V

2005-11-01

The purpose of the study was to compare delivery methods of lecture material regarding contraceptive options by either traditional or interactive lecture style with the use of an audience response system with obstetrics and gynecology residents. A prospective, randomized controlled trial that included 17 obstetrics and gynecology residents was conducted. Group differences and comparison of pre/posttest scores to evaluate efficacy of lecture styles were performed with the Student t test. Each participant completed an evaluation to assess usefulness of the audience response system. Residents who received audience response system interactive lectures showed a 21% improvement between pretest and posttest scores; residents who received the standard lecture demonstrated a 2% improvement (P = .018). The evaluation survey showed that 82% of residents thought that the audience response system was a helpful learning aid. The results of this randomized controlled trial demonstrate the effectiveness of audience response system for knowledge retention, which suggests that it may be an efficient teaching tool for residency education.

ERP correlates of attentional processing in spider fear: evidence of threat-specific hypervigilance.

PubMed

Venetacci, Rebecca; Johnstone, Amber; Kirkby, Kenneth C; Matthews, Allison

2018-05-01

Attentional bias towards threat can be demonstrated by enhanced processing of threat-related targets and/or greater interference when threat-related distractors are present. These effects are argued to reflect processing within the orienting and executive control networks of the brain respectively. This study investigated behavioural (RT) and electrophysiological correlates of early selective attention and top-down attentional control among females with high (n = 16) or low (n = 16) spider fear (Mean age = 22 years). Participants completed a novel flanker go/nogo task in which a central schematic flower or spider stimulus was flanked by either congruent or incongruent distractors. Participants responded to green stimuli (go trials) and withheld response to yellow stimuli (nogo trials). High fear participants demonstrated significantly shorter reaction times and greater P1 amplitude to spider targets, suggesting specific hypervigilance towards threat-relevant stimuli. In contrast to predictions, there was little evidence for behavioural interference effects or differences in N2 amplitude when distractor stimuli were threat-relevant.

Reducing mental illness stigma in health care students and professionals: a review of the literature.

PubMed

Stubbs, Alison

2014-12-01

The aim of this study was to examine the effectiveness of interventions designed to reduce mental illness stigma among healthcare students and professionals. A literature search was conducted using the Cochrane Library and PubMed. Randomised controlled trial level evidence demonstrated that interventions involving direct contact, indirect filmed contact or an educational email effectively reduced stigma in the short term. Role play was the only intervention with randomised controlled trial level evidence demonstrating no effect. There was not enough evidence to suggest that any intervention can maintain stigma reduction over time. Stigma reduction in healthcare students and professionals needs to be sustained over time if it is to result in positive changes for people living with mental illness. Further research is needed to determine which interventions, if any, can achieve this. Only then will large-scale implementation of a stigma reduction intervention be feasible and beneficial to people living with mental illness. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Can pelvic floor muscle training improve sexual function in women with pelvic organ prolapse? A randomized controlled trial.

PubMed

Braekken, Ingeborg H; Majida, Memona; Ellström Engh, Marie; Bø, Kari

2015-02-01

Pelvic floor muscle training (PFMT) has level 1 evidence of reducing the size and symptoms associated with pelvic organ prolapse (POP). There is scant knowledge, however, regarding whether PFMT has an effect on sexual function. The aim of the trial was to evaluate the effect of PFMT on sexual function in women with POP. In this randomized controlled trial, 50 women were randomized to an intervention group (6 months of PFMT and lifestyle advice) and 59 women were randomized to a control group (lifestyle advice only). Participants completed a validated POP-specific questionnaire to describe frequency and bother of prolapse, bladder, bowel, and sexual symptoms and answered a semi-structured interview. No significant change in number of women being sexually active was reported. There were no significant differences between groups regarding change in satisfaction with frequency of intercourse. Interview data revealed that 19 (39%) of women in the PFMT group experienced improved sexual function vs. two (5%) in the control group (P<0.01). Specific improvements reported by some of the women were increased control, strength and awareness of the pelvic floor, improved self-confidence, sensation of a "tighter" vagina, improved libido and orgasms, resolution of pain with intercourse, and heightened sexual gratification for partners. Women who described improved sexual function demonstrated the greatest increases in pelvic floor muscle (PFM) strength (mean 16 ± 10 cmH2 0) and endurance (mean 150 ± 140 cmH2 0s) (P<0.01). PFMT can improve sexual function in some women. Women reporting improvement in sexual function demonstrated the greatest increase in PFM strength and endurance. © 2014 International Society for Sexual Medicine.

Recent developments in the clinical pharmacology of rolapitant: subanalyses in specific populations

PubMed Central

Rapoport, Bernardo Leon; Aapro, Matti; Chasen, Martin R; Jordan, Karin; Navari, Rudolph M; Schnadig, Ian; Schwartzberg, Lee

2017-01-01

Knowledge of the involvement of the neurokinin substance P in emesis has led to the development of the neurokinin-1 receptor antagonists (NK-1 RAs) for control of chemotherapy-induced nausea and vomiting (CINV), in combination with serotonin type 3 receptor antagonists and corticosteroids. The NK-1 RA rolapitant, recently approved in oral formulation, has nanomolar affinity for the NK-1 receptor, as do the other commercially available NK-1 RAs, aprepitant and netupitant. Rolapitant is rapidly absorbed and has a long half-life in comparison to aprepitant and netupitant. All three NK-1 RAs undergo metabolism by cytochrome P450 (CYP) 3A4, necessitating caution with the concomitant use of CYP3A4 inhibitors, but in contrast to aprepitant and netupitant, rolapitant does not inhibit or induce CYP3A4. However, rolapitant is a moderate inhibitor of CYP2D6, and concomitant use with CYP2D6 substrates with narrow therapeutic indices should be avoided. Aprepitant, netupitant, and rolapitant have all demonstrated efficacy in the control of delayed CINV in patients receiving moderately and highly emetogenic chemotherapy in randomized controlled trials, including over multiple cycles of chemotherapy. We reviewed recent post hoc analyses of clinical trial data demonstrating that rolapitant is efficacious in the control of CINV in patient populations with specific tumor types, namely, breast cancers, gastrointestinal/colorectal cancers, and lung cancers. In addition, we show that rolapitant has efficacy in the control of CINV in specific age groups of patients receiving chemotherapy (<65 and ≥65 years of age). Overall, the safety profile of rolapitant in these specific patient populations was consistent with that observed in primary analyses of phase 3 trials. PMID:28919712

Feasibility trial of a Spanish-language multimedia educational intervention.

PubMed

Wells, Kristen J; McIntyre, Jessica; Gonzalez, Luis E; Lee, Ji-Hyun; Fisher, Kate J; Jacobsen, Paul B; Meade, Cathy; Muñoz-Antonia, Teresita; Quinn, Gwendolyn P

2013-10-01

Hispanic cancer patients are underrepresented in clinical trials; research suggests lack of knowledge and language barriers contribute to low accrual. Multimedia materials offer advantages to Hispanic populations because they have high acceptability, are easy to disseminate, and can be viewed with family. Hispanic cancer patients and caregivers participated in focus groups to aid in developing a Spanish-language multimedia intervention to educate Hispanic cancer patients about clinical trials. We explored the feasibility of delivering the intervention in medical oncology clinics. A total of 35 patients were randomized to either the multimedia intervention group (n = 18) or a control group (n = 17) who were asked to read the National Cancer Institute's Spanish-language clinical trials brochure. Self-reported data on knowledge about and attitudes toward clinical trials, self-efficacy for participating in a clinical trial, intention to participate in a clinical trial if asked, and receptivity to information about a clinical trial were collected at baseline and 10 days later. Delivery of the multimedia presentation in oncology clinics was feasible. The intervention group had more knowledge about clinical trials at follow-up than the control group; scores for intention to participate in a clinical trial by participants in the intervention group increased from 3.8 to 4.0 of a possible 5, but declined in the control group from 4.5 to 4.1. No statistically significant difference was detected between groups in scores for attitudes or self-efficacy for making a decision to participate in a clinical trial. Our sample size was inadequate to identify differences between the informational methods. Although all patients were asked about their willingness to participate in a clinical trial, this decision was hypothetical. In addition, the study was conducted with a sample of Spanish-speaking Hispanic cancer patients at a comprehensive cancer center in Florida. Thus, the results may not generalize to other Hispanic populations. In the pilot project, we demonstrated the feasibility of delivering multimedia information to patients in medical oncology clinics. Because delivery in a clinical setting was found to be feasible, a larger study should be conducted to evaluate the efficacy of the multimedia intervention with respect to promoting accrual of Hispanic patients to clinical trials.

Combined cognitive-strategy and task-specific training improves transfer to untrained activities in sub-acute stroke: An exploratory randomized controlled trial

PubMed Central

McEwen, Sara; Polatajko, Helene; Baum, Carolyn; Rios, Jorge; Cirone, Dianne; Doherty, Meghan; Wolf, Timothy

2014-01-01

Purpose The purpose of this study was to estimate the effect of the Cognitive Orientation to daily Occupational Performance (CO-OP) approach compared to usual outpatient rehabilitation on activity and participation in people less than 3 months post stroke. Methods An exploratory, single blind, randomized controlled trial with a usual care control arm was conducted. Participants referred to 2 stroke rehabilitation outpatient programs were randomized to receive either Usual Care or CO-OP. The primary outcome was actual performance of trained and untrained self-selected activities, measured using the Performance Quality Rating Scale (PQRS). Additional outcomes included the Canadian Occupational Performance Measure (COPM), the Stroke Impact Scale Participation Domain, the Community Participation Index, and the Self Efficacy Gauge. Results Thirty-five (35) eligible participants were randomized; 26 completed the intervention. Post-intervention, PQRS change scores demonstrated CO-OP had a medium effect over Usual Care on trained self-selected activities (d=0.5) and a large effect on untrained (d=1.2). At a 3 month follow-up, PQRS change scores indicated a large effect of CO-OP on both trained (d=1.6) and untrained activities (d=1.1). CO-OP had a small effect on COPM and a medium effect on the Community Participation Index perceived control and the Self-Efficacy Gauge. Conclusion CO-OP was associated with a large treatment effect on follow up performances of self-selected activities, and demonstrated transfer to untrained activities. A larger trial is warranted. PMID:25416738

Combined Cognitive-Strategy and Task-Specific Training Improve Transfer to Untrained Activities in Subacute Stroke: An Exploratory Randomized Controlled Trial.

PubMed

McEwen, Sara; Polatajko, Helene; Baum, Carolyn; Rios, Jorge; Cirone, Dianne; Doherty, Meghan; Wolf, Timothy

2015-07-01

The purpose of this study was to estimate the effect of the Cognitive Orientation to daily Occupational Performance (CO-OP) approach compared with usual outpatient rehabilitation on activity and participation in people <3 months poststroke. An exploratory, single-blind, randomized controlled trial, with a usual-care control arm, was conducted. Participants referred to 2 stroke rehabilitation outpatient programs were randomized to receive either usual care or CO-OP. The primary outcome was actual performance of trained and untrained self-selected activities, measured using the Performance Quality Rating Scale (PQRS). Additional outcomes included the Canadian Occupational Performance Measure (COPM), the Stroke Impact Scale Participation Domain, the Community Participation Index, and the Self-Efficacy Gauge. A total of 35 eligible participants were randomized; 26 completed the intervention. Post intervention, PQRS change scores demonstrated that CO-OP had a medium effect over usual care on trained self-selected activities (d = 0.5) and a large effect on untrained activities (d = 1.2). At a 3-month follow-up, PQRS change scores indicated a large effect of CO-OP on both trained (d = 1.6) and untrained activities (d = 1.1). CO-OP had a small effect on COPM and a medium effect on the Community Participation Index perceived control and on the Self-Efficacy Gauge. CO-OP was associated with a large treatment effect on follow-up performances of self-selected activities and demonstrated transfer to untrained activities. A larger trial is warranted. © The Author(s) 2014.

Care delivery and self-management strategies for children with epilepsy.

PubMed

Lindsay, Bruce; Bradley, Peter M

2010-12-08

Epilepsy care for children has been criticised for its lack of impact. Various service models and strategies have been developed in response to perceived inadequacies in care provision for children and their families. We set out to compare the effectiveness of specialist or dedicated teams or individuals in the care of children with epilepsy with usual care services. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library February issue, 2010), MEDLINE (1950 to March 2010), EMBASE (1988 to May 2006*), PsycINFO (1806 to March 2010) and CINAHL (1982 to March 2010).*Please note that as we currently do not have access to EMBASE, we have been unable to update this aspect of our searching. We included randomised controlled trials, controlled or matched trials, cohort studies or other prospective studies with a control group, or time series studies. Each review author independently selected studies, extracted data and assessed the quality of included studies. Four trials and five reports are included in this review. They report on four different education and counselling programmes for children, children and parents, or teenagers and parents. Each programme showed some benefits for the well-being of children with epilepsy, but each trial had methodological flaws and no single programme was evaluated by more than one study. While each of the programmes in this review showed some benefit to children with epilepsy their impacts were extremely variable. No programme showed benefits across the full range of outcomes. No study appears to have demonstrated any detrimental effects but the evidence in favour of any single programme is insufficient to make it possible to recommend one programme rather than another. More trials, carried out by independent research teams, are needed.

Using short-term evidence to predict six-month outcomes in clinical trials of signs and symptoms in rheumatoid arthritis.

PubMed

Nixon, Richard M; Bansback, Nick; Stevens, John W; Brennan, Alan; Madan, Jason

2009-01-01

A model is presented to generate a distribution for the probability of an ACR response at six months for a new treatment for rheumatoid arthritis given evidence from a one- or three-month clinical trial. The model is based on published evidence from 11 randomized controlled trials on existing treatments. A hierarchical logistic regression model is used to find the relationship between the proportion of patients achieving ACR20 and ACR50 at one and three months and the proportion at six months. The model is assessed by Bayesian predictive P-values that demonstrate that the model fits the data well. The model can be used to predict the number of patients with an ACR response for proposed six-month clinical trials given data from clinical trials of one or three months duration. Copyright 2008 John Wiley & Sons, Ltd.

A PARENT–ADOLESCENT INTERVENTION TO INCREASE SEXUAL RISK COMMUNICATION: RESULTS OF A RANDOMIZED CONTROLLED TRIAL

PubMed Central

Villarruel, Antonia M.; Cherry, Carol Loveland; Cabriales, Esther Gallegos; Ronis, David L.; Zhou, Yan

2009-01-01

This article reports results of a randomized controlled trial designed to test an intervention to increase parent–adolescent sexual risk communication among Mexican parents. Data were analyzed from parents (n = 791) randomly assigned to an HTV risk reduction or health promotion intervention. Measures were administered at pretest, posttest, and 6– and 12–month follow–ups. Generalized estimation equation (GEE) analysis indicates parents in the HIV risk reduction intervention reported significantly more general communication (p < .005), more sexual risk communication (p < .001) and more comfort with communication (p < .001) than parents in the control intervention. Behavioral, normative, and control beliefs significantly mediated the effect of the intervention on all communication outcomes. This study demonstrates the efficacy of an intervention to increase the quality and quantity of parent–adolescent communication related to general and sex–specific communication. PMID:18956979

Effectiveness of short-term, enhanced, infection control support in improving compliance with infection control guidelines and practice in nursing homes: a cluster randomized trial.

PubMed

Gopal Rao, G; Jeanes, A; Russell, H; Wilson, D; Atere-Roberts, E; O'Sullivan, D; Donaldson, N

2009-10-01

In this prospective cluster randomized controlled trial we evaluated the impact of short-term provision of enhanced infection control support on infection control practice in nursing homes in South London. Twelve nursing homes were recruited, six each in intervention (300 residents) and control (265 residents) groups. Baseline observations of hand hygiene facilities, environmental cleanliness and safe disposal of clinical waste showed poor compliance in both groups. Post-intervention observations showed improvement in both groups. There was no statistical difference between the two groups in the compliance for hand hygiene facilities (P=0.69); environmental cleanliness (P=0.43) and safe disposal of clinical waste (P=0.96). In both groups, greatest improvement was in compliance with safe disposal of clinical waste and the least improvement was in hand hygiene facilities. Since infection control practice improved in intervention and control groups, we could not demonstrate that provision of short-term, enhanced, infection control support in nursing homes had a significant impact in infection control practice.

A Clustered Randomized Controlled Trial of the Positive Prevention PLUS Adolescent Pregnancy Prevention Program.

PubMed

LaChausse, Robert G

2016-09-01

To determine the impact of Positive Prevention PLUS, a school-based adolescent pregnancy prevention program on delaying sexual intercourse, birth control use, and pregnancy. I randomly assigned a diverse sample of ninth grade students in 21 suburban public high schools in California into treatment (n = 2483) and control (n = 1784) groups that participated in a clustered randomized controlled trial. Between October 2013 and May 2014, participants completed baseline and 6-month follow-up surveys regarding sexual behavior and pregnancy. Participants in the treatment group were offered Positive Prevention PLUS, an 11-lesson adolescent pregnancy prevention program. The program had statistically significant impacts on delaying sexual intercourse and increasing the use of birth control. However, I detected no program effect on pregnancy rates at 6-month follow-up. The Positive Prevention PLUS program demonstrated positive impacts on adolescent sexual behavior. This suggests that programs that focus on having students practice risk reduction skills may delay sexual activity and increase birth control use.

Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial.

PubMed

Fröbert, Ole; Götberg, Matthias; Angerås, Oskar; Jonasson, Lena; Erlinge, David; Engstrøm, Thomas; Persson, Jonas; Jensen, Svend E; Omerovic, Elmir; James, Stefan K; Lagerqvist, Bo; Nilsson, Johan; Kåregren, Amra; Moer, Rasmus; Yang, Cao; Agus, David B; Erglis, Andrejs; Jensen, Lisette O; Jakobsen, Lars; Christiansen, Evald H; Pernow, John

2017-07-01

Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new AMI, or stent thrombosis at 1 year. The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Endovascular therapy for acute ischemic stroke.

PubMed

Broderick, Joseph P

2009-03-01

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

A randomized controlled trial of the effectiveness of a pre-recruitment primer letter to increase participation in a study of colorectal screening and surveillance.

PubMed

Paul, Christine; Courtney, Ryan; Sanson-Fisher, Rob; Carey, Mariko; Hill, David; Simmons, Jody; Rose, Shiho

2014-04-01

Recruiting cancer patients is a barrier often encountered in research trials. However, very few randomized trials explore strategies to improve participation rates. The purpose of this study was to evaluate the effectiveness of a pre-recruitment primer letter to recruit persons diagnosed with colorectal cancer for a research trial. Potentially eligible participants were identified by the Victorian Cancer Registry. A total of 1,062 participants were randomized to receive either a mailed explanatory primer letter designed to encourage research participation, or no primer letter. Two weeks after the intervention, the Victorian Cancer Registry sought permission from patients to release their contact details to researchers. Those who agreed were contacted and invited to the study. Pre-recruitment encouragement was not effective at increasing recruitment, with no significant differences demonstrated between experimental groups. Overall, 40% (n = 425) consented to participate, 25% (n = 243) refused and 35% (n = 394) did not respond. While this study demonstrated disappointing outcomes, pre-recruitment letters should not be ruled out as an approach altogether. Rather, future research should explore whether other factors to increase motivation, such as intensity and timing, are feasible and acceptable for contacting cancer patients. Australian and New Zealand Clinical Trials Registry, ACTRN12609000628246.

Toward mHealth Brief Contact Interventions in Suicide Prevention: Case Series From the Suicide Intervention Assisted by Messages (SIAM) Randomized Controlled Trial

PubMed Central

Mesmeur, Catherine; Gravey, Michel; Billot, Romain; Walter, Michel; Lemey, Christophe; Lenca, Philippe

2018-01-01

Background Research indicates that maintaining contact either via letter or postcard with at-risk adults following discharge from care services after a suicide attempt (SA) can reduce reattempt risk. Pilot studies have demonstrated that interventions using mobile health (mHealth) technologies are feasible in a suicide prevention setting. Objective The aim of this study was to report three cases of patients recruited in the Suicide Intervention Assisted by Messages (SIAM) study to describe how a mobile intervention may influence follow-up. Methods SIAM is a 2-year, multicenter randomized controlled trial conducted by the Brest University Hospital, France. Participants in the intervention group receive SIAM text messages 48 hours after discharge, then at day 8 and day 15, and months 1, 2, 3, 4, 5, and 6. The study includes participants aged 18 years or older, who have attended a participating hospital for an SA, and have been discharged from the emergency department (ED) or a psychiatric unit (PU) for a stay of less than 7 days. Eligible participants are randomized between the SIAM intervention messages and a control group. In this study, we present three cases from the ongoing SIAM study that demonstrate the capability of a mobile-based brief contact intervention for triggering patient-initiated contact with a crisis support team at various time points throughout the mobile-based follow-up period. Results Out of the 244 patients recruited in the SIAM randomized controlled trial, three cases were selected to illustrate the impact of mHealth on suicide risk management. Participants initiated contact with the emergency crisis support service after receiving text messages up to 6 months following discharge from the hospital. Contact was initiated immediately following receipt of a text message or up to 6 days following a message. Conclusions This text message–based brief contact intervention has demonstrated the potential to reconnect suicidal individuals with crisis support services while they are experiencing suicidal ideation as well as in a period after receiving messages. As follow-up phone calls over an extended period of time may not be feasible, this intervention has the potential to offer simple technological support for individuals following discharge from the ED. Trial Registration ClinicalTrials.gov NCT02106949; https://clinicaltrials.gov/ct2/show/NCT02106949 (Archived by WebCite at http://www.webcitation.org/6wMtAFL49) PMID:29321126

MiDAS ENCORE: Randomized Controlled Clinical Trial Report of 6-Month Results.

PubMed

Staats, Peter S; Benyamin, Ramsin M

2016-02-01

Patients suffering from neurogenic claudication due to lumbar spinal stenosis (LSS) often experience moderate to severe pain and significant functional disability. Neurogenic claudication results from progressive degenerative changes in the spine, and most often affects the elderly. Both the MILD® procedure and epidural steroid injections (ESIs) offer interventional pain treatment options for LSS patients experiencing neurogenic claudication refractory to more conservative therapies. MILD provides an alternative to ESIs via minimally invasive lumbar decompression. Prospective, multi-center, randomized controlled clinical trial. Twenty-six US interventional pain management centers. To compare patient outcomes following treatment with either MILD (treatment group) or ESIs (active control group) in LSS patients with neurogenic claudication and verified ligamentum flavum hypertrophy. This prospective, multi-center, randomized controlled clinical trial includes 2 study arms with a 1-to-1 randomization ratio. A total of 302 patients were enrolled, with 149 randomized to MILD and 153 to the active control. Six-month follow-up has been completed and is presented in this report. In addition, one year follow-up will be conducted for patients in both study arms, and supplementary 2 year outcome data will be collected for patients in the MILD group only. Outcomes are assessed using the Oswestry Disability Index (ODI), numeric pain rating scale (NPRS) and Zurich Claudication Questionnaire (ZCQ). Primary efficacy is the proportion of ODI responders, tested for statistical superiority of the MILD group versus the active control group. ODI responders are defined as patients achieving the validated Minimal Important Change (MIC) of =10 point improvement in ODI from baseline to follow-up. Similarly, secondary efficacy includes proportion of NPRS and ZCQ responders using validated MIC thresholds. Primary safety is the incidence of device or procedure-related adverse events in each group. At 6 months, all primary and secondary efficacy results provided statistically significant evidence that MILD is superior to the active control. For primary efficacy, the proportion of ODI responders in the MILD group (62.2%) was statistically significantly higher than for the epidural steroid group (35.7%) (P < 0.001). Further, all secondary efficacy parameters demonstrated statistical superiority of MILD versus the active control. The primary safety endpoint was achieved, demonstrating that there is no difference in safety between MILD and ESIs (P = 1.00). Limitations include lack of patient blinding due to considerable differences in treatment protocols, and a potentially higher non-responder rate for both groups versus standard-of-care due to study restrictions on adjunctive pain therapies. Six month follow-up data from this trial demonstrate that the MILD procedure is statistically superior to epidural steroids, a known active treatment for LSS patients with neurogenic claudication and verified central stenosis due to ligamentum flavum hypertrophy. The results of all primary and secondary efficacy outcome measures achieved statistically superior outcomes in the MILD group versus ESIs. Further, there were no statistically significant differences in the safety profile between study groups. This prospective, multi-center, randomized controlled clinical trial provides strong evidence of the effectiveness of MILD versus epidural steroids in this patient population. NCT02093520.

A cluster randomized controlled trial of the Promoting Alternative Thinking Strategies (PATHS) curriculum.

PubMed

Humphrey, Neil; Barlow, Alexandra; Wigelsworth, Michael; Lendrum, Ann; Pert, Kirsty; Joyce, Craig; Stephens, Emma; Wo, Lawrence; Squires, Garry; Woods, Kevin; Calam, Rachel; Turner, Alex

2016-10-01

This randomized controlled trial (RCT) evaluated the efficacy of the Promoting Alternative Thinking Strategies curriculum (PATHS; Kusche & Greenberg, 1994) as a means to improve children's social-emotional competence (assessed via the Social Skills Improvement System (SSIS); Gresham & Elliot, 2008) and mental health outcomes (assessed via the Strengths and Difficulties Questionnaire (SDQ); Goodman, 1997). Forty-five schools in Greater Manchester, England, were randomly assigned to treatment and control groups. Allocation was balanced by proportions of children eligible for free school meals and speaking English as an additional language via minimization. Children (N=4516) aged 7-9years at baseline in the participating schools were the target cohort. During the two-year trial period, teachers of this cohort in schools allocated to the intervention group delivered the PATHS curriculum, while their counterparts in the control group continued their usual provision. Teachers in PATHS schools received initial training and on-going support and assistance from trained coaches. Hierarchical linear modeling of outcome data was undertaken to identify both primary (e.g., for all children) and secondary (e.g., for children classified as "at-risk") intervention effects. A primary effect of the PATHS curriculum was found, demonstrating increases in teacher ratings of changes in children's social-emotional competence. Additionally, secondary effects of PATHS were identified, showing reductions in teacher ratings of emotional symptoms and increases in pro-social behavior and child ratings of engagement among children identified as at-risk at baseline. However, our analyses also identified primary effects favoring the usual provision group, showing reductions in teacher ratings of peer problems and emotional symptoms, and secondary effects demonstrating reductions in teacher ratings of conduct problems and child ratings of co-operation among at-risk children. Effect sizes were small in all cases. These mixed findings suggest that social and emotional learning interventions such as PATHS may not be as efficacious when implemented outside their country of origin and evaluated in independent trials. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

A randomized controlled trial of Pivotal Response Treatment Group for parents of children with autism.

PubMed

Hardan, Antonio Y; Gengoux, Grace W; Berquist, Kari L; Libove, Robin A; Ardel, Christina M; Phillips, Jennifer; Frazier, Thomas W; Minjarez, Mendy B

2015-08-01

With rates of autism diagnosis continuing to rise, there is an urgent need for effective and efficient service delivery models. Pivotal Response Treatment (PRT) is considered an established treatment for autism spectrum disorder (ASD); however, there have been few well-controlled studies with adequate sample size. The aim of this study was to conduct a randomized controlled trial to evaluate PRT parent training group (PRTG) for targeting language deficits in young children with ASD. Fifty-three children with autism and significant language delay between 2 and 6 years old were randomized to PRTG (N = 27) or psychoeducation group (PEG; N = 26) for 12 weeks. The PRTG taught parents behavioral techniques to facilitate language development. The PEG taught general information about ASD (clinical trial NCT01881750; http://www.clinicaltrials.gov). Analysis of child utterances during the structured laboratory observation (primary outcome) indicated that, compared with children in the PEG, children in the PRTG demonstrated greater improvement in frequency of utterances (F(2, 43) = 3.53, p = .038, d = 0.42). Results indicated that parents were able to learn PRT in a group format, as the majority of parents in the PRTG (84%) met fidelity of implementation criteria after 12 weeks. Children also demonstrated greater improvement in adaptive communication skills (Vineland-II) following PRTG and baseline Mullen visual reception scores predicted treatment response to PRTG. This is the first randomized controlled trial of group-delivered PRT and one of the largest experimental investigations of the PRT model to date. The findings suggest that specific instruction in PRT results in greater skill acquisition for both parents and children, especially in functional and adaptive communication skills. Further research in PRT is warranted to replicate the observed results and address other core ASD symptoms. © 2014 Association for Child and Adolescent Mental Health.

Structure and content components of self-management interventions that improve health-related quality of life in people with inflammatory bowel disease: a systematic review, meta-analysis and meta-regression.

PubMed

Tu, Wenjing; Xu, Guihua; Du, Shizheng

2015-10-01

The purpose of this review was to identify and categorise the components of the content and structure of effective self-management interventions for patients with inflammatory bowel disease. Inflammatory bowel diseases are chronic gastrointestinal disorders impacting health-related quality of life. Although the efficacy of self-management interventions has been demonstrated in previous studies, the most effective components of the content and structure of these interventions remain unknown. A systematic review, meta-analysis and meta-regression of randomised controlled trials was used. A systematic search of six electronic databases, including Pubmed, Embase, Cochrane central register of controlled trials, Web of Science, Cumulative Index of Nursing and Allied Health Literature and Chinese Biomedical Literature Database, was conducted. Content analysis was used to categorise the components of the content and structure of effective self-management interventions for inflammatory bowel disease. Clinically important and statistically significant beneficial effects on health-related quality of life were explored, by comparing the association between effect sizes and various components of self-management interventions such as the presence or absence of specific content and different delivery methods. Fifteen randomised controlled trials were included in this review. Distance or remote self-management interventions demonstrated a larger effect size. However, there is no evidence for a positive effect associated with specific content component of self-management interventions in adult patients with inflammatory bowel disease in general. The results showed that self-management interventions have positive effects on health-related quality of life in patients with inflammatory bowel disease, and distance or remote self-management programmes had better outcomes than other types of interventions. This review provides useful information to clinician and researchers when determining components of effective self-management programmes for patients with inflammatory bowel disease. More high-quality randomised controlled trials are needed to test the results. © 2015 John Wiley & Sons Ltd.

Examining the Efficacy of the Modified Story Memory Technique (mSMT) in Persons With TBI Using Functional Magnetic Resonance Imaging (fMRI): The TBI-MEM Trial.

PubMed

Chiaravalloti, Nancy D; Dobryakova, Ekaterina; Wylie, Glenn R; DeLuca, John

2015-01-01

New learning and memory deficits are common following traumatic brain injury (TBI). Yet few studies have examined the efficacy of memory retraining in TBI through the most methodologically vigorous randomized clinical trial. Our previous research has demonstrated that the modified Story Memory Technique (mSMT) significantly improves new learning and memory in multiple sclerosis. The present double-blind, placebo-controlled, randomized clinical trial examined changes in cerebral activation on functional magnetic resonance imaging following mSMT treatment in persons with TBI. Eighteen individuals with TBI were randomly assigned to treatment (n = 9) or placebo (n = 9) groups. Baseline and follow-up functional magnetic resonance imaging was collected during a list-learning task. Significant differences in cerebral activation from before to after treatment were noted in regions belonging to the default mode network and executive control network in the treatment group only. Results are interpreted in light of these networks. Activation differences between the groups likely reflect increased use of strategies taught during treatment. This study demonstrates a significant change in cerebral activation resulting from the mSMT in a TBI sample. Findings are consistent with previous work in multiple sclerosis. Behavioral interventions can show significant changes in the brain, validating clinical utility.

Real-time Ensemble Flow Forecasts for a 2017 Mock Operation Test Trial of Forecast Informed Reservoir Operations for Lake Mendocino in Mendocino County, California

NASA Astrophysics Data System (ADS)

Delaney, C.; Mendoza, J.; Jasperse, J.; Hartman, R. K.; Whitin, B.; Kalansky, J.

2017-12-01

Forecast informed reservoir operations (FIRO) is a methodology that incorporates short to mid-range precipitation and flow forecasts to inform the flood operations of reservoirs. The Ensemble Forecast Operations (EFO) alternative is a probabilistic approach of FIRO that incorporates 15-day ensemble streamflow predictions (ESPs) made by NOAA's California-Nevada River Forecast Center (CNRFC). With the EFO approach, release decisions are made to manage forecasted risk of reaching critical operational thresholds. A water management model was developed for Lake Mendocino, a 111,000 acre-foot reservoir located near Ukiah, California, to conduct a mock operation test trial of the EFO alternative for 2017. Lake Mendocino is a dual use reservoir, which is owned and operated for flood control by the United States Army Corps of Engineers and is operated for water supply by the Sonoma County Water Agency. Due to recent changes in the operations of an upstream hydroelectric facility, this reservoir has suffered from water supply reliability issues since 2007. The operational trial utilized real-time ESPs prepared by the CNRFC and observed flow information to simulate hydrologic conditions in Lake Mendocino and a 50-mile downstream reach of the Russian River to the City of Healdsburg. Results of the EFO trial demonstrate a 6% increase in reservoir storage at the end of trial period (May 10) relative to observed conditions. Additionally, model results show no increase in flows above flood stage for points downstream of Lake Mendocino. Results of this investigation and other studies demonstrate that the EFO alternative may be a viable flood control operations approach for Lake Mendocino and warrants further investigation through additional modeling and analysis.

Can oral 5-aminosalicylic acid be administered once daily in the treatment of mild-to-moderate ulcerative colitis? A meta-analysis of randomized-controlled trials.

PubMed

Zhu, Ying; Tang, Ren-Kuan; Zhao, Peng; Zhu, Shi-sheng; Li, Yong-guo; Li, Jian-bo

2012-05-01

Several trials have demonstrated that oral delayed-release mesalamine might be administered once daily. We aimed to conduct a meta-analysis to investigate this. A comprehensive and multiple-source literature search was carried out. Only randomized-controlled trials (RCTs) were investigated by comparing a once daily-dosing regime with a divided (twice or thrice daily)-dosing regime of oral delayed-release mesalamine formulations for induction or maintenance of remission in patients with mild-to-moderate ulcerative colitis. The quality of RCTs was assessed using the Jadad scores. Meta-analysis of pooled odds ratios was carried out using Review Manager 5.1. Nine RCTs were finally included. With regard to meta-analyses for induction trials, there were no significant differences for all comparisons between the once daily and the divided groups, including maintenance of just clinical remission (P=0.52) and just endoscopic remission (P=0.23), maintenance of combined clinical and endoscopic remission (P=0.78), and the overall incidence of adverse events (P=0.61). With regard to meta-analyses for maintenance trials, there were also no significant differences for all comparisons between once daily and divided groups, including maintenance of just clinical remission (P=0.73) and just endoscopic remission (P=0.43), maintenance of combined clinical and endoscopic remission (P=0.43), the overall incidence of adverse events (P=0.12) as well as compliance with the prescribed medication (P=0.34). The present work showed that oral delayed-release mesalazine administered as a single or a divided dose demonstrated a good safety profile, which was well tolerated and effective as either maintenance or induction treatment. High clinical and/or endoscopic remission rates can be achieved with once-daily dosing.

Topical intra-articular compared with intravenous tranexamic acid to reduce blood loss in primary total knee replacement: a double-blind, randomized, controlled, noninferiority clinical trial.

PubMed

Gomez-Barrena, Enrique; Ortega-Andreu, Miguel; Padilla-Eguiluz, Norma G; Pérez-Chrzanowska, Hanna; Figueredo-Zalve, Reyes

2014-12-03

Abundant literature regarding the use of intravenous tranexamic acid (TXA) in primary total knee replacement is available. Randomized controlled trials have confirmed the efficacy of topical TXA compared with placebo, but the comparison between topical and intravenous TXA is unclear. The present study was designed to verify noninferior efficacy and safety of topical intra-articular TXA compared with intravenous TXA in primary total knee replacement with cemented implants. A Phase-III, single-center, double-blind, randomized, controlled clinical trial was performed to compare topical intra-articular TXA (3 g of TXA in 100 mL of physiological saline solution) with two intravenous doses of TXA (15 mg/kg in 100 mL of physiological saline solution, one dose before tourniquet release and another three hours after surgery) in a multimodal protocol for blood loss prevention. The primary outcome was the blood transfusion rate, and the secondary outcomes included visible blood loss (as measured in the drain) at twenty-four hours postoperatively and invisible blood loss (as estimated from the Nadler formula) at forty-eight hours postoperatively. The sample size of seventy-eight patients was calculated to give a statistical power of 99% for demonstrating noninferiority. Thirty-nine patients each were allocated to receive topical intra-articular TXA (the experimental group) and intravenous TXA (the control group); there were no significant differences in demographics or preoperative laboratory values between the groups. Noninferiority was estimated by comparing the confidence intervals with a delta of 10%. Student t and Mann-Whitney tests were used to assess the significance of any differences. The transfusion rate was zero in both groups; thus, noninferiority was demonstrated for the primary efficacy end point, suggesting equivalence. Noninferiority was also demonstrated for the secondary efficacy end points. Drain blood loss at twenty-four hours was 315.6 mL (95% confidence interval [CI], 248.5 to 382.7 mL) in the experimental group and 308.1 mL (95% CI, 247.6 to 368.5 mL) in the control group (p = 0.948, Mann-Whitney). Also, estimated blood loss at forty-eight hours was 1259.0 mL (95% CI, 1115.6 to 1402.3 mL) in the experimental group and 1317.9 mL (95% CI, 1175.4 to 1460.4 mL) in the control group (p = 0.837, Mann-Whitney). No significant safety differences were seen between groups. Topical administration of TXA according to the described protocol demonstrated noninferiority compared with intravenous TXA, with no safety concerns. This randomized controlled trial supports the topical intra-articular administration of TXA in primary total knee replacement with cemented implants. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Chlorambucil for the treatment of patients with chronic lymphocytic leukemia (CLL) - a systematic review and meta-analysis of randomized trials.

PubMed

Vidal, Liat; Gurion, Ronit; Ram, Ron; Raanani, Pia; Bairey, Osnat; Robak, Tadeusz; Gafter-Gvili, Anat; Shpilberg, Ofer

2016-09-01

Randomized clinical trials that compared chlorambucil to different regimens, for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) do not support an overall survival (OS) benefit. To assess the efficacy and safety of chlorambucil as frontline treatment, we conducted a systematic review and meta-analysis of randomized controlled trials. OS was the primary outcome. Meta-analysis of 18 trials that compared purine analogs, alkylators, alemtuzumab and ibrutinib to chlorambucil demonstrated no OS benefit for therapy without chlorambucil over chlorambucil (pooled HR 0.99, 95% CI 0.91-1.08; 4133 patients). PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection. The risk of secondary malignancies was not increased with chlorambucil. In conclusion, our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL. Purine analogs should be preferred in fit younger patients because of longer PFS. Future trials should focus on unfit patients who are underrepresented in clinical trials.

Changing cluster composition in cluster randomised controlled trials: design and analysis considerations

PubMed Central

2014-01-01

Background There are many methodological challenges in the conduct and analysis of cluster randomised controlled trials, but one that has received little attention is that of post-randomisation changes to cluster composition. To illustrate this, we focus on the issue of cluster merging, considering the impact on the design, analysis and interpretation of trial outcomes. Methods We explored the effects of merging clusters on study power using standard methods of power calculation. We assessed the potential impacts on study findings of both homogeneous cluster merges (involving clusters randomised to the same arm of a trial) and heterogeneous merges (involving clusters randomised to different arms of a trial) by simulation. To determine the impact on bias and precision of treatment effect estimates, we applied standard methods of analysis to different populations under analysis. Results Cluster merging produced a systematic reduction in study power. This effect depended on the number of merges and was most pronounced when variability in cluster size was at its greatest. Simulations demonstrate that the impact on analysis was minimal when cluster merges were homogeneous, with impact on study power being balanced by a change in observed intracluster correlation coefficient (ICC). We found a decrease in study power when cluster merges were heterogeneous, and the estimate of treatment effect was attenuated. Conclusions Examples of cluster merges found in previously published reports of cluster randomised trials were typically homogeneous rather than heterogeneous. Simulations demonstrated that trial findings in such cases would be unbiased. However, simulations also showed that any heterogeneous cluster merges would introduce bias that would be hard to quantify, as well as having negative impacts on the precision of estimates obtained. Further methodological development is warranted to better determine how to analyse such trials appropriately. Interim recommendations include avoidance of cluster merges where possible, discontinuation of clusters following heterogeneous merges, allowance for potential loss of clusters and additional variability in cluster size in the original sample size calculation, and use of appropriate ICC estimates that reflect cluster size. PMID:24884591

Practical Effects of Classwide Mathematics Intervention

ERIC Educational Resources Information Center

VanDerHeyden, Amanda M.; Codding, Robin S.

2015-01-01

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

A new approach for strawberry disease control

USDA-ARS?s Scientific Manuscript database

Here, we report a new approach demonstrating the killing power of UV-C treatment against fungal pathogens without damaging strawberry plants. UV-C light was followed by a specific dark period. Field trials also included applications of microbial antagonists twice a week. The dark period most like...

Effect of a mobile app intervention on vegetable consumption in overweight adults: a randomized controlled trial.

PubMed

Mummah, Sarah; Robinson, Thomas N; Mathur, Maya; Farzinkhou, Sarah; Sutton, Stephen; Gardner, Christopher D

2017-09-15

Mobile applications (apps) have been heralded as transformative tools to deliver behavioral health interventions at scale, but few have been tested in rigorous randomized controlled trials. We tested the effect of a mobile app to increase vegetable consumption among overweight adults attempting weight loss maintenance. Overweight adults (n=135) aged 18-50 years with BMI=28-40 kg/m 2 near Stanford, CA were recruited from an ongoing 12-month weight loss trial (parent trial) and randomly assigned to either the stand-alone, theory-based Vegethon mobile app (enabling goal setting, self-monitoring, and feedback and using "process motivators" including fun, surprise, choice, control, social comparison, and competition) or a wait-listed control condition. The primary outcome was daily vegetables servings, measured by an adapted Harvard food frequency questionnaire (FFQ) 8 weeks post-randomization. Daily vegetable servings from 24-hour dietary recalls, administered by trained, certified, and blinded interviewers 5 weeks post-randomization, was included as a secondary outcome. All analyses were conducted according to principles of intention-to-treat. Daily vegetable consumption was significantly greater in the intervention versus control condition for both measures (adjusted mean difference: 2.0 servings; 95% CI: 0.1, 3.8, p=0.04 for FFQ; and 1.0 servings; 95% CI: 0.2, 1.9; p=0.02 for 24-hour recalls). Baseline vegetable consumption was a significant moderator of intervention effects (p=0.002) in which effects increased as baseline consumption increased. These results demonstrate the efficacy of a mobile app to increase vegetable consumption among overweight adults. Theory-based mobile interventions may present a low-cost, scalable, and effective approach to improving dietary behaviors and preventing associated chronic diseases. ClinicalTrials.gov NCT01826591. Registered 27 March 2013.

Cluster Randomized Controlled Trial

PubMed Central

Young, John; Chapman, Katie; Nixon, Jane; Patel, Anita; Holloway, Ivana; Mellish, Kirste; Anwar, Shamaila; Breen, Rachel; Knapp, Martin; Murray, Jenni; Farrin, Amanda

2015-01-01

Background and Purpose— We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers, linked to evidence-based treatment algorithms and reference guides (the longer-term stroke care system of care) to address the poor longer-term recovery experienced by many patients with stroke. Methods— A pragmatic, multicentre, cluster randomized controlled trial of this system of care. Eligible patients referred to community-based Stroke Care Coordinators were randomized to receive the new system of care or usual practice. The primary outcome was improved patient psychological well-being (General Health Questionnaire-12) at 6 months; secondary outcomes included functional outcomes for patients, carer outcomes, and cost-effectiveness. Follow-up was through self-completed postal questionnaires at 6 and 12 months. Results— Thirty-two stroke services were randomized (29 participated); 800 patients (399 control; 401 intervention) and 208 carers (100 control; 108 intervention) were recruited. In intention to treat analysis, the adjusted difference in patient General Health Questionnaire-12 mean scores at 6 months was −0.6 points (95% confidence interval, −1.8 to 0.7; P=0.394) indicating no evidence of statistically significant difference between the groups. Costs of Stroke Care Coordinator inputs, total health and social care costs, and quality-adjusted life year gains at 6 months, 12 months, and over the year were similar between the groups. Conclusions— This robust trial demonstrated no benefit in clinical or cost-effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ISRCTN 67932305. PMID:26152298

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

PubMed Central

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

2016-01-01

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

Dissociable Fronto-Operculum-Insula Control Signals for Anticipation and Detection of Inhibitory Sensory Cue.

PubMed

Cai, Weidong; Chen, Tianwen; Ide, Jaime S; Li, Chiang-Shan R; Menon, Vinod

2017-08-01

The ability to anticipate and detect behaviorally salient stimuli is important for virtually all adaptive behaviors, including inhibitory control that requires the withholding of prepotent responses when instructed by external cues. Although right fronto-operculum-insula (FOI), encompassing the anterior insular cortex (rAI) and inferior frontal cortex (rIFC), involvement in inhibitory control is well established, little is known about signaling mechanisms underlying their differential roles in detection and anticipation of salient inhibitory cues. Here we use 2 independent functional magnetic resonance imaging data sets to investigate dynamic causal interactions of the rAI and rIFC, with sensory cortex during detection and anticipation of inhibitory cues. Across 2 different experiments involving auditory and visual inhibitory cues, we demonstrate that primary sensory cortex has a stronger causal influence on rAI than on rIFC, suggesting a greater role for the rAI in detection of salient inhibitory cues. Crucially, a Bayesian prediction model of subjective trial-by-trial changes in inhibitory cue anticipation revealed that the strength of causal influences from rIFC to rAI increased significantly on trials in which participants had higher anticipation of inhibitory cues. Together, these results demonstrate the dissociable bottom-up and top-down roles of distinct FOI regions in detection and anticipation of behaviorally salient cues across multiple sensory modalities. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ketamine for pain in adults and children with cancer: a systematic review and synthesis of the literature.

PubMed

Bredlau, Amy Lee; Thakur, Rajbala; Korones, David Nathan; Dworkin, Robert H

2013-10-01

Chronic cancer pain is often refractory and difficult to treat. Ketamine is a medication with evidence of efficacy in the treatment of chronic pain. This article presents a synthesis of the data on ketamine for refractory cancer pain in adults and children. There are five randomized, double-blind, controlled trials of ketamine use in cancer pain that demonstrate improvement in pain for some patients. There are six prospective, uncontrolled trials in cancer pain that also demonstrate improvement in pain scores for some patients. There are no randomized, controlled trials in children with cancer pain, although there are a few studies reflecting improved pain control with ketamine for children with cancer pain. Adverse events for adults on ketamine are most commonly somnolence, feelings of insobriety, nausea/vomiting, hallucinations, depersonalization/derealization, and drowsiness. However, when ketamine is combined with benzodiazepines, feelings of insobriety, hallucinations, and depersonalization/derealization are not reported. Children on ketamine have had few reported adverse effects, which include sedation, anorexia, urinary retention, and myoclonic movements. Recommended ketamine infusion dosages are from 0.05 to 0.5 mg/kg/h (intravenous or subcutaneous). Recommended oral dosages of ketamine are 0.2-0.5 mg/kg/dose two to three times daily with a maximum of 50 mg/dose three times daily. Despite limitations in the breadth and depth of data available, there is evidence that ketamine may be a viable option for treatment-refractory cancer pain. Wiley Periodicals, Inc.

The influence of short-chain essential fatty acids on children with attention-deficit/hyperactivity disorder: a double-blind placebo-controlled study.

PubMed

Raz, Raanan; Carasso, Rafael L; Yehuda, Shlomo

2009-04-01

Essential fatty acids (EFA) are needed for normal sensory, cognitive, and motor function. The EFA blood profile seems to be different in children with attention-deficit/hyperactivity disorder (ADHD) as compared to matched controls. Previous open EFA supplementation trials were successful in demonstrating significant therapeutic effects in this population, whereas most of the randomized controlled trials failed to show any benefit over placebo. The current randomized, double-blind, placebo-controlled trial tested the influence of short-chain EFA supplementation on ADHD children, using parent and teacher questionnaires and a computerized continuous performance test. A total of 73 unmedicated children aged 7-13 years with a diagnosis of ADHD participated in the study; 63 children completed the study. The EFA supplement contained 480 mg of linoleic acid and 120 mg of alpha-linolenic acid, and the placebo contained 1000 mg of vitamin C (daily amounts); both were given for a 7-week supplementation period. Analysis of variance for repeated measures revealed that both treatments ameliorated some of the symptoms, but no significant differences were found between the groups in any of the treatment effects.

Specific treatment of problems of the spine (STOPS): design of a randomised controlled trial comparing specific physiotherapy versus advice for people with subacute low back disorders

PubMed Central

2011-01-01

Background Low back disorders are a common and costly cause of pain and activity limitation in adults. Few treatment options have demonstrated clinically meaningful benefits apart from advice which is recommended in all international guidelines. Clinical heterogeneity of participants in clinical trials is hypothesised as reducing the likelihood of demonstrating treatment effects, and sampling of more homogenous subgroups is recommended. We propose five subgroups that allow the delivery of specific physiotherapy treatment targeting the pathoanatomical, neurophysiological and psychosocial components of low back disorders. The aim of this article is to describe the methodology of a randomised controlled trial comparing specific physiotherapy treatment to advice for people classified into five subacute low back disorder subgroups. Methods/Design A multi-centre parallel group randomised controlled trial is proposed. A minimum of 250 participants with subacute (6 weeks to 6 months) low back pain and/or referred leg pain will be classified into one of five subgroups and then randomly allocated to receive either physiotherapy advice (2 sessions over 10 weeks) or specific physiotherapy treatment (10 sessions over 10 weeks) tailored according to the subgroup of the participant. Outcomes will be assessed at 5 weeks, 10 weeks, 6 months and 12 months following randomisation. Primary outcomes will be activity limitation measured with a modified Oswestry Disability Index as well as leg and back pain intensity measured on separate 0-10 Numerical Rating Scales. Secondary outcomes will include a 7-point global rating of change scale, satisfaction with physiotherapy treatment, satisfaction with treatment results, the Sciatica Frequency and Bothersomeness Scale, quality of life (EuroQol-5D), interference with work, and psychosocial risk factors (Orebro Musculoskeletal Pain Questionnaire). Adverse events and co-interventions will also be measured. Data will be analysed according to intention to treat principles, using linear mixed models for continuous outcomes, Mann Whitney U tests for ordinal outcomes, and Chi-square, risk ratios and risk differences for dichotomous outcomes. Discussion This trial will determine the difference in outcomes between specific physiotherapy treatment tailored to each of the five subgroups versus advice which is recommended in guidelines as a suitable treatment for most people with a low back disorder. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000834257. PMID:21599941

Commentary: considerations for using the 'Trials within Cohorts' design in a clinical trial of an investigational medicinal product.

PubMed

Bibby, Anna C; Torgerson, David J; Leach, Samantha; Lewis-White, Helen; Maskell, Nick A

2018-01-08

The 'trials within cohorts' (TwiC) design is a pragmatic approach to randomised trials in which trial participants are randomly selected from an existing cohort. The design has multiple potential benefits, including the option of conducting multiple trials within the same cohort. To date, the TwiC design methodology been used in numerous clinical settings but has never been applied to a clinical trial of an investigational medicinal product (CTIMP). We have recently secured the necessary approvals to undertake the first CTIMP using the TwiC design. In this paper, we describe some of the considerations and modifications required to ensure such a trial is compliant with Good Clinical Practice and international clinical trials regulations. We advocate using a two-stage consent process and using the consent stages to explicitly differentiate between trial participants and cohort participants who are providing control data. This distinction ensured compliance but had consequences with respect to costings, recruitment and the trial assessment schedule. We have demonstrated that it is possible to secure ethical and regulatory approval for a CTIMP TwiC. By including certain considerations at the trial design stage, we believe this pragmatic and efficient methodology could be utilised in other CTIMPs in future.

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). Methods and design This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic range; 3) Number of INR determinations within the therapeutic range in the first six weeks of treatment. Discussion To date, there are no clinical trials comparing pharmacogenetic acenocoumarol dosing algorithm versus routine clinical practice in VTE. Implementation of this pharmacogenetic algorithm in the clinical practice routine could reduce side effects and improve patient safety. Trial registration Eudra CT. Identifier: 2009-016643-18. PMID:23237631

Randomized controlled trial of mailed Nicotine Replacement Therapy to Canadian smokers: study protocol.

PubMed

Cunningham, John A; Leatherdale, Scott T; Selby, Peter L; Tyndale, Rachel F; Zawertailo, Laurie; Kushnir, Vladyslav

2011-09-28

Considerable public health efforts are ongoing Canada-wide to reduce the prevalence of smoking in the general population. From 1985 to 2005, smoking rates among adults decreased from 35% to 19%, however, since that time, the prevalence has plateaued at around 18-19%. To continue to reduce the number of smokers at the population level, one option has been to translate interventions that have demonstrated clinical efficacy into population level initiatives. Nicotine Replacement Therapy (NRT) has a considerable clinical research base demonstrating its efficacy and safety and thus public health initiatives in Canada and other countries are distributing NRT widely through the mail. However, one important question remains unanswered--do smoking cessation programs that involve mailed distribution of free NRT work? To answer this question, a randomized controlled trial is required. A single blinded, panel survey design with random assignment to an experimental and a control condition will be used in this study. A two-stage recruitment process will be employed, in the context of a general population survey with two follow-ups (8 weeks and 6 months). Random digit dialing of Canadian home telephone numbers will identify households with adult smokers (aged 18+ years) who are willing to take part in a smoking study that involves three interviews, with saliva collection for 3-HC/cotinine ratio measurement at baseline and saliva cotinine verification at 8-week and 6-month follow-ups (N = 3,000). Eligible subjects interested in free NRT will be determined at baseline (N = 1,000) and subsequently randomized into experimental and control conditions to receive versus not receive nicotine patches. The primary hypothesis is that subjects who receive nicotine patches will display significantly higher quit rates (as assessed by 30 day point prevalence of abstinence from tobacco) at 6-month follow-up as compared to subjects who do not receive nicotine patches at baseline. The findings from the proposed trial are timely and highly relevant as mailed distribution of NRT require considerable resources and there are limited public health dollars available to combat this substantial health concern. In addition, findings from this randomized controlled trial will inform the development of models to engage smokers to quit, incorporating proactive recruitment and the offer of evidence based treatment. ClinicalTrials.gov: NCT01429129.

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

PubMed

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

2018-01-01

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

Is reflexology an effective intervention? A systematic review of randomised controlled trials.

PubMed

Ernst, Edzard

2009-09-07

To evaluate the evidence for and against the effectiveness of reflexology for treating any medical condition. Six electronic databases were searched from their inception to February 2009 to identify all relevant randomised controlled trials (RCTs). No language restrictions were applied. RCTs of reflexology delivered by trained reflexologists to patients with specific medical conditions. Condition studied, study design and controls, primary outcome measures, follow-up, and main results were extracted. 18 RCTs met all the inclusion criteria. The studies examined a range of conditions: anovulation, asthma, back pain, dementia, diabetes, cancer, foot oedema in pregnancy, headache, irritable bowel syndrome, menopause, multiple sclerosis, the postoperative state and premenstrual syndrome. There were > 1 studies for asthma, the postoperative state, cancer palliation and multiple sclerosis. Five RCTs yielded positive results. Methodological quality was evaluated using the Jadad scale. The methodological quality was often poor, and sample sizes were generally low. Most higher-quality trials did not generate positive findings. The best evidence available to date does not demonstrate convincingly that reflexology is an effective treatment for any medical condition.

Virtual colonoscopy, optical colonoscopy, or fecal occult blood testing for colorectal cancer screening: results of a pilot randomized controlled trial.

PubMed

You, John J; Liu, Yudong; Kirby, John; Vora, Parag; Moayyedi, Paul

2015-07-09

No head-to-head randomized controlled trials have demonstrated the superiority of one colorectal screening modality over another in reducing colorectal cancer mortality. We conducted a pilot randomized controlled trial of fecal occult blood testing (FOBT), optical colonoscopy (OC), and virtual colonoscopy (VC), to inform the planning of a larger evaluative trial. Eligible patients (aged 50 to 70) were recruited from five primary care practices in Hamilton, ON, Canada, between March 23, 2010 and August 11, 2010, and randomized 1:1:1 in a parallel design using an automated, centralized telephone service to either FOBT, OC, or VC. To reflect conventional practice, patients received no additional reminders to complete their allocated screening test beyond those received in usual practice. The primary outcome was completion of the assigned screening procedure. Results of the index test and any follow-up investigations were ascertained at 6 months. Participants, caregivers, and outcome assessors were not blinded to group assignment. The trial was stopped early due to lack of ongoing funding. A total of 198 participants were enrolled, of whom 67 were allocated to FOBT, 66 to OC, and 65 to VC. The allocated screening procedure was completed by 43 (64%) subjects allocated to FOBT (95% confidence interval [CI], 52-75%), 53 (80%) subjects allocated to OC (95% CI, 69-88%), and 50 (77%) subjects allocated to VC (95% CI, 65-85%); because the trial stopped early, we had insufficient statistical power to detect clinically relevant differences in completion rates. During 6 months follow-up, colorectal adenomas were detected in 0 (0%) subjects allocated to FOBT, 12 (18%) subjects allocated to OC, and 2 (3%) subjects allocated to VC. One subject in the OC arm had histological evidence of high-grade dysplasia. No subjects were diagnosed with colorectal cancer. In this pilot randomized controlled trial of colorectal cancer screening in a primary care setting, 64-80% of subjects completed their allocated screening test. These findings may be of value to investigators planning clinical trials to evaluate the effectiveness of colorectal cancer screening. ClinicalTrials.gov NCT00865527. https://clinicaltrials.gov/ct2/show/NCT00865527.

Modulation of cognitive control levels via manipulation of saccade trial-type probability assessed with event-related BOLD fMRI.

PubMed

Pierce, Jordan E; McDowell, Jennifer E

2016-02-01

Cognitive control supports flexible behavior adapted to meet current goals and can be modeled through investigation of saccade tasks with varying cognitive demands. Basic prosaccades (rapid glances toward a newly appearing stimulus) are supported by neural circuitry, including occipital and posterior parietal cortex, frontal and supplementary eye fields, and basal ganglia. These trials can be contrasted with complex antisaccades (glances toward the mirror image location of a stimulus), which are characterized by greater functional magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) signal in the aforementioned regions and recruitment of additional regions such as dorsolateral prefrontal cortex. The current study manipulated the cognitive demands of these saccade tasks by presenting three rapid event-related runs of mixed saccades with a varying probability of antisaccade vs. prosaccade trials (25, 50, or 75%). Behavioral results showed an effect of trial-type probability on reaction time, with slower responses in runs with a high antisaccade probability. Imaging results exhibited an effect of probability in bilateral pre- and postcentral gyrus, bilateral superior temporal gyrus, and medial frontal gyrus. Additionally, the interaction between saccade trial type and probability revealed a strong probability effect for prosaccade trials, showing a linear increase in activation parallel to antisaccade probability in bilateral temporal/occipital, posterior parietal, medial frontal, and lateral prefrontal cortex. In contrast, antisaccade trials showed elevated activation across all runs. Overall, this study demonstrated that improbable performance of a typically simple prosaccade task led to augmented BOLD signal to support changing cognitive control demands, resulting in activation levels similar to the more complex antisaccade task. Copyright © 2016 the American Physiological Society.

The efficacy of electroacupuncture for the treatment of simple female stress urinary incontinence - comparison with pelvic floor muscle training: study protocol for a multicenter randomized controlled trial.

PubMed

Su, Tongsheng; Zhou, Jing; Liu, Zhishun; Chen, Yuelai; Zhang, Wei; Chu, Haoran; Luo, Qiong; Lu, Jin; An, Junming; Liu, Baoyan

2015-02-08

Previous research has shown that electroacupuncture therapy has a potential therapeutic effect for simple female stress urinary incontinence. In this study, pelvic floor muscle training, the first-line treatment for stress urinary incontinence in women based on meta-analysis of numerous randomized control trials and recommended by international clinical practice, is used as a control group to demonstrate whether electroacupuncture therapy is a better method for female stress urinary incontinence. A randomized controlled trial has been designed to evaluate the therapeutic benefit of electroacupuncture for female stress urinary incontinence compared with pelvic floor muscle training. The safety of electroacupuncture and patient compliance will also be evaluated. Untoward reaction to the electroacupuncture, including a broken needle, fainting on acupuncture, or pain during acupuncture, will be recorded and the therapy will be stopped if an untoward reaction occurs. After we have received full ethical approval and patient consent, participants will be randomized to receive a series of 24 electroacupuncture or pelvic floor muscle training interventions. The frequency and amount of leakage will be measured as the primary outcome parameters. Secondary outcome parameters include the 1-hour pad test, the short-form of the International Consultation on Incontinence Questionnaire, patient subjective effectiveness evaluation, weekly usage of pad, and usage of specialty therapy for female stress urinary incontinence. This trial will help to determine whether electroacupuncture is a more effective treatment than pelvic floor muscle training for patients with female stress urinary incontinence. ClinicalTrials.gov NCT01940432 (12 September 2013).

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PubMed

Sahraian, Ali; Jahromi, Leila Razeghian; Ghanizadeh, Ahmad; Mowla, Arash

2017-04-01

The aim of this study is to examine the effects of memantine as an adjuvant treatment for obsessive compulsive (OC) symptoms in patients with bipolar disorder (BD) type I, manic phase. In this 16-week double-blind placebo-controlled randomized clinical trial, 58 patients in the manic phase of BD who had OC symptoms were randomly allocated to receive memantine or placebo plus their routine medications (lithium + olanzapine + clonazepam). The Yale Brown Obsessive Compulsive Behavior Scale was used to assess the outcomes. Adverse effects were also recorded. Thirty-eight patients (19 in the memantine group and 19 in the placebo group) completed the trial. Throughout the trial, the mean score decreased from 20.26 ± 5.91 to 9.73 ± 5.44 in the memantine group (P < 0.000) and from 22.89 ± 5.70 to 16.63 ± 4.00 in the placebo group (P < 0.000). At the end of the study, 15 (78.94%) patients in the memantine group and 7 (36.84%) patients in the placebo group demonstrated more than 34% decline in the Yale Brown Obsessive Compulsive Behavior Scale score (P < 0.01). No serious adverse effects were reported. Our double-blind controlled clinical trial showed that memantine is an effective adjuvant agent for reducing OC symptoms in patients with BD. However, it needs to be noted that our study is preliminary, and larger double-blind controlled studies are needed to confirm the results.

Incentives for smoking cessation.

PubMed

Cahill, Kate; Hartmann-Boyce, Jamie; Perera, Rafael

2015-05-18

Material or financial incentives are widely used in an attempt to precipitate or reinforce behaviour change, including smoking cessation. They operate in workplaces, in clinics and hospitals, and to a lesser extent within community programmes. In this third update of our review we now include trials conducted in pregnant women, to reflect the increasing activity and resources now targeting this high-risk group of smokers. To determine whether incentives and contingency management programmes lead to higher long-term quit rates. We searched the Cochrane Tobacco Addiction Group Specialised Register, with additional searches of MEDLINE, EMBASE, CINAHL and PsycINFO. The most recent searches were in December 2014, although we also include two trials published in 2015. We considered randomised controlled trials, allocating individuals, workplaces, groups within workplaces, or communities to experimental or control conditions. We also considered controlled studies with baseline and post-intervention measures. We include studies in a mixed-population setting (e.g. community-, work-, institution-based), and also, for this update, trials in pregnant smokers. One author (KC) extracted data and a second (JH-B) checked them. We contacted study authors for additional data where necessary. The main outcome measure in the mixed-population studies was abstinence from smoking at longest follow-up, and at least six months from the start of the intervention. In the trials of pregnant smokers abstinence was measured at the longest follow-up, and at least to the end of the pregnancy. Twenty-one mixed-population studies met our inclusion criteria, covering more than 8400 participants. Ten studies were set in clinics or health centres, one in Thai villages served by community health workers, two in academic institutions, and the rest in worksites. All but six of the trials were run in the USA. The incentives included lottery tickets or prize draws, cash payments, vouchers for goods and groceries, and in six trials the recovery of money deposited by those taking part. The odds ratio (OR) for quitting with incentives at longest follow-up (six months or more) compared with controls was 1.42 (95% confidence interval (CI) 1.19 to 1.69; 17 trials, [20 comparisons], 7715 participants). Only three studies demonstrated significantly higher quit rates for the incentives group than for the control group at or beyond the six-month assessment: One five-arm USA trial compared rewards- and deposit-based interventions at individual and group level, with incentives available up to USD 800 per quitter, and demonstrated a quit rate in the rewards groups of 8.1% at 12 months, compared with 4.7% in the deposits groups. A direct comparison between the rewards-based and the deposit-based groups found a benefit for the rewards arms, with an OR at 12 months of 1.76 (95% CI 1.22 to 2.53; 2070 participants). Although more people in this trial accepted the rewards programmes than the deposit programmes, the proportion of quitters in each group favoured the deposit-refund programme. Another USA study rewarded both participation and quitting up to USD 750, and achieved sustained quit rates of 9.4% in the incentives group compared with 3.6% for the controls. A deposit-refund trial in Thailand also achieved significantly higher quit rates in the intervention group (44.2%) compared with the control group (18.8%), but uptake was relatively low, at 10.5%. In the remaining trials, there was no clear evidence that participants who committed their own money to the programme did better than those who did not, or that contingent rewards enhanced success rates over fixed payment schedules. We rated the overall quality of the older studies as low, but with later trials (post-2000) more likely to meet current standards of methodology and reporting.Eight of nine trials with usable data in pregnant smokers (seven conducted in the USA and one in the UK) delivered an adjusted OR at longest follow-up (up to 24 weeks post-partum) of 3.60 (95% CI 2.39 to 5.43; 1295 participants, moderate-quality studies) in favour of incentives. Three of the trials demonstrated a clear benefit for contingent rewards; one delivered monthly vouchers to confirmed quitters and to their designated 'significant other supporter', achieving a quit rate in the intervention group of 21.4% at two months post-partum, compared with 5.9% among the controls. Another trial offered a scaled programme of rewards for the percentage of smoking reduction achieved over the course of the 12-week intervention, and achieved an intervention quit rate of 31% at six weeks post-partum, compared with no quitters in the control group. The largest (UK-based) trial provided intervention quitters with up to GBP 400-worth of vouchers, and achieved a quit rate of 15.4% at longest follow-up, compared to the control quit rate of 4%. Four trials confirmed that payments made to reward a successful quit attempt (i.e. contingent), compared to fixed payments for attending the antenatal appointment (non-contingent), resulted in higher quit rates. Front-loading of rewards to counteract early withdrawal symptoms made little difference to quit rates. Incentives appear to boost cessation rates while they are in place. The two trials recruiting from work sites that achieved sustained success rates beyond the reward schedule concentrated their resources into substantial cash payments for abstinence. Such an approach may only be feasible where independently-funded smoking cessation programmes are already available, and within a relatively affluent and educated population. Deposit-refund trials can suffer from relatively low rates of uptake, but those who do sign up and contribute their own money may achieve higher quit rates than reward-only participants. Incentive schemes conducted among pregnant smokers improved the cessation rates, both at the end-of-pregnancy and post-partum assessments. Current and future research might continue to explore the scale, loading and longevity of possible cash or voucher reward schedules, within a variety of smoking populations.

Investigating Inhibitory Control in Children with Epilepsy: An fMRI Study

PubMed Central

Triplett, Regina L.; Velanova, Katerina; Luna, Beatriz; Padmanabhan, Aarthi; Gaillard, William D.; Asato, Miya R.

2014-01-01

SUMMARY Objective Deficits in executive function are increasingly noted in children with epilepsy and have been associated with poor academic and psychosocial outcomes. Impaired inhibitory control contributes to executive dysfunction in children with epilepsy; however, its neuroanatomic basis has not yet been investigated. We used functional Magnetic Resonance Imaging (fMRI) to probe the integrity of activation in brain regions underlying inhibitory control in children with epilepsy. Methods This cross-sectional study consisted of 34 children aged 8 to 17 years: 17 with well-controlled epilepsy and 17 age-and sex-matched controls. Participants performed the antisaccade (AS) task, representative of inhibitory control, during fMRI scanning. We compared AS performance during neutral and reward task conditions and evaluated task-related blood-oxygen level dependent (BOLD) activation. Results Children with epilepsy demonstrated impaired AS performance compared to controls during both neutral (non-reward) and reward trials, but exhibited significant task improvement during reward trials. Post-hoc analysis revealed that younger patients made more errors than older patients and all controls. fMRI results showed preserved activation in task-relevant regions in patients and controls, with the exception of increased activation in the left posterior cingulate gyrus in patients specifically with generalized epilepsy across neutral and reward trials. Significance Despite impaired inhibitory control, children with epilepsy accessed typical neural pathways as did their peers without epilepsy. Children with epilepsy showed improved behavioral performance in response to the reward condition, suggesting potential benefits of the use of incentives in cognitive remediation. PMID:25223606

Does Preoperative Radio(chemo)therapy Increase Anastomotic Leakage in Rectal Cancer Surgery? A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Qin, Changjiang; Ren, Xuequn; Xu, Kaiwu; Chen, Zhihui; He, Yulong; Song, Xinming

2014-01-01

Objective. Preoperative radio(chemo)therapy (pR(C)T) appears to increase postoperative complications of rectal cancer resection, but clinical trials have reported conflicting results. The objective of this meta-analysis was performed to assess the effects of pR(C)T on anastomotic leak after rectal cancer resection. Methods. PubMed, Embase, and the Cochrane Library were searched from January 1980 to January 2014. Randomized controlled trials included all original articles reporting anastomotic leak in patients with rectal cancer, among whom some received preoperative radiotherapy or chemoradiotherapy while others did not. The analysed end-points were the anastomotic leak. Result. Seven randomized controlled trials with 3375 patients were included in the meta-analysis. 1660 forming the group undergoing preoperative radiotherapy or chemoradiotherapy versus 1715 patients undergoing without preoperative radiotherapy or chemoradiotherapy. The meta-analyses found that pR(C)T was not an independent risk factor for anastomotic leakage (OR 1.02, 95% CI 0.80–1.30; P = 0.88). Subgroups analysis was performed and the result was not altered. Conclusions. Current evidence demonstrates that pR(C)T did not increase the risk of postoperative anastomotic leak after rectal cancer resection in patients. PMID:25477955

Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study.

PubMed

Alahdab, Fares; Farah, Wigdan; Almasri, Jehad; Barrionuevo, Patricia; Zaiem, Feras; Benkhadra, Raed; Asi, Noor; Alsawas, Mouaz; Pang, Yifan; Ahmed, Ahmed T; Rajjo, Tamim; Kanwar, Amrit; Benkhadra, Khalid; Razouki, Zayd; Murad, M Hassan; Wang, Zhen

2018-03-01

To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias. Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Columnar processing in primate pFC: evidence for executive control microcircuits.

PubMed

Opris, Ioan; Hampson, Robert E; Gerhardt, Greg A; Berger, Theodore W; Deadwyler, Sam A

2012-12-01

A common denominator for many cognitive disorders of human brain is the disruption of neural activity within pFC, whose structural basis is primarily interlaminar (columnar) microcircuits or "minicolumns." The importance of this brain region for executive decision-making has been well documented; however, because of technological constraints, the minicolumnar basis is not well understood. Here, via implementation of a unique conformal multielectrode recording array, the role of interlaminar pFC minicolumns in the executive control of task-related target selection is demonstrated in nonhuman primates performing a visuomotor DMS task. The results reveal target-specific, interlaminar correlated firing during the decision phase of the trial between multielectrode recording array-isolated minicolumnar pairs of neurons located in parallel in layers 2/3 and layer 5 of pFC. The functional significance of individual pFC minicolumns (separated by 40 μm) was shown by reduced correlated firing between cell pairs within single minicolumns on error trials with inappropriate target selection. To further demonstrate dependence on performance, a task-disrupting drug (cocaine) was administered in the middle of the session, which also reduced interlaminar firing in minicolumns that fired appropriately in the early (nondrug) portion of the session. The results provide a direct demonstration of task-specific, real-time columnar processing in pFC indicating the role of this type of microcircuit in executive control of decision-making in primate brain.

The Neural Mechanisms Underlying the Decision to Rest in the Presence of Fatigue: A Magnetoencephalography Study

PubMed Central

Ishii, Akira; Tanaka, Masaaki; Watanabe, Yasuyoshi

2014-01-01

Adequate rest is essential to avoid fatigue and disruption of homeostasis. However, the neural mechanisms underlying the decision to rest are not well understood. In the present study, we aimed to clarify the neural mechanisms of this decision-making process using magnetoencephalography. Fifteen healthy volunteers participated in decision and control experiments performed in a cross-over fashion. In the decision experiment, participants performed 1,200 reverse Stroop test trials and were intermittently asked to decide whether they wanted to take a rest or continue. In the control experiments, participants performed 1,200 reverse Stroop test trials and were instructed to press a response button intermittently without making any decision. Changes in oscillatory brain activity were assessed using a narrow-band adaptive spatial filtering method. The levels of decrease in theta (4–8 Hz) band power in left Brodmann's area (BA) 31, alpha (8–13 Hz) band power in left BA 10 and BA 9, and beta (13–25 Hz) band power in right BA 46 and left BA 10 were greater in trials when the participant opted to rest (rest trials) than those in control trials. The decrease in theta band power in BA 31 in the rest trials was positively correlated with the subjective level of fatigue after the decision experiment. These results demonstrated that the dorsolateral prefrontal cortex, frontal pole, and posterior cingulate cortex play a role in the decision to rest in the presence of fatigue. These findings may help clarify the neural mechanisms underlying fatigue and fatigue-related problems. PMID:25303465

Disruption of Darna pallivitta (Lepidoptera: Limacodidae) by Conventional and Mobile Pheromone Deployment

PubMed Central

Siderhurst, Matthew S.; Jang, Eric B.; Carvalho, Lori A. F. N.; Nagata, Janice T.; Derstine, Nathan T.

2015-01-01

Identification of the Darna pallivitta (Moore) pheromone component n-butyl (E)-7,9-decadienoate (E7,9-10:COOn-Bu) has made it possible to investigate communication disruption to control this lepidopteran pest. Conventional communication disruption trials showed marked decreases in the mean number of male moths captured in E7,9-10:COOnBu-treated fields compared with control fields. For traps baited with E7,9-10:COOnBu, percent disruptions were 94.4% and 92.1% for septa (1 g pheromone/ha, 1-wk trial duration) and spirals (6 g pheromone/ha, 8-wk trial duration) respectively. For traps baited with virgin female moths, percent disruption was 73.3% using septa disruptors (1 g pheromone/ha, 1-wk trial duration). Mobile communication disruption using Bactrocera cucurbitae (Coquillett) as carriers for E7,9-10:COOn-Bu was evaluated in the following three areas: fly survivorship, attraction of male moths to treated flies, and moth disruption in a small-scale field trial. Topical application of E7,9-10:COOnBu showed no significant decrease in survivorship at 50 and 80 µg/fly. However, decreased survivorship was observed at 100 µg/fly and linear regression showed E7,9-10:COOnBu dose was significantly correlated with B. cucurbitae survivorship. Traps containing honey–pheromone-fed flies attracted and caught D. pallivitta over a 1-wk period, demonstrating the attractiveness of the carrier. Releasing E7,9-10:COOnBu-fed B. cucurbitae (∼2 g pheromone/ha, 1-wk trial duration) resulted in significantly reduced trap catches in treatment fields compared with control fields on the first 2 d of the field trial. Percent disruptions were 84.7% (day 1) and 56.0% (day 2). These results suggest that both conventional communication disruption and mobile communication disruption have potential to control D. pallivitta. PMID:26078301

Secular trend, seasonality and effects of a community-based intervention on neonatal mortality: follow-up of a cluster-randomised trial in Quang Ninh province, Vietnam.

PubMed

Eriksson, Leif; Nga, Nguyen T; Hoa, Dinh T Phuong; Duc, Duong M; Bergström, Anna; Wallin, Lars; Målqvist, Mats; Ewald, Uwe; Huy, Tran Q; Thuy, Nguyen T; Do, Tran Thanh; Lien, Pham T L; Persson, Lars-Åke; Selling, Katarina Ekholm

2018-05-15

Little is know about whether the effects of community engagement interventions for child survival in low-income and middle-income settings are sustained. Seasonal variation and secular trend may blur the data. Neonatal mortality was reduced in a cluster-randomised trial in Vietnam where laywomen facilitated groups composed of local stakeholders employing a problem-solving approach for 3 years. In this analysis, we aim at disentangling the secular trend, the seasonal variation and the effect of the intervention on neonatal mortality during and after the trial. In Quang Ninh province, 44 communes were allocated to intervention and 46 to control. Births and neonatal deaths were assessed in a baseline survey in 2005, monitored during the trial in 2008-2011 and followed up by a survey in 2014. Time series analyses were performed on monthly neonatal mortality data. There were 30 187 live births and 480 neonatal deaths. The intervention reduced the neonatal mortality from 19.1 to 11.6 per 1000 live births. The reduction was sustained 3 years after the trial. The control areas reached a similar level at the time of follow-up. Time series decomposition analysis revealed a downward trend in the intervention areas during the trial that was not found in the control areas. Neonatal mortality peaked in the hot and wet summers. A community engagement intervention resulted in a lower neonatal mortality rate that was sustained but not further reduced after the end of the trial. When decomposing time series of neonatal mortality, a clear downward trend was demonstrated in intervention but not in control areas. ISRCTN44599712, Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Disruption of Darna pallivitta (Lepidoptera: Limacodidae) by Conventional and Mobile Pheromone Deployment.

PubMed

Siderhurst, Matthew S; Jang, Eric B; Carvalho, Lori A F N; Nagata, Janice T; Derstine, Nathan T

2015-01-01

Identification of the Darna pallivitta (Moore) pheromone component n-butyl (E)-7,9-decadienoate (E7,9-10:COOn-Bu) has made it possible to investigate communication disruption to control this lepidopteran pest. Conventional communication disruption trials showed marked decreases in the mean number of male moths captured in E7,9-10:COOnBu-treated fields compared with control fields. For traps baited with E7,9-10:COOnBu, percent disruptions were 94.4% and 92.1% for septa (1 g pheromone/ha, 1-wk trial duration) and spirals (6 g pheromone/ha, 8-wk trial duration) respectively. For traps baited with virgin female moths, percent disruption was 73.3% using septa disruptors (1 g pheromone/ha, 1-wk trial duration). Mobile communication disruption using Bactrocera cucurbitae (Coquillett) as carriers for E7,9-10:COOn-Bu was evaluated in the following three areas: fly survivorship, attraction of male moths to treated flies, and moth disruption in a small-scale field trial. Topical application of E7,9-10:COOnBu showed no significant decrease in survivorship at 50 and 80 µg/fly. However, decreased survivorship was observed at 100 µg/fly and linear regression showed E7,9-10:COOnBu dose was significantly correlated with B. cucurbitae survivorship. Traps containing honey-pheromone-fed flies attracted and caught D. pallivitta over a 1-wk period, demonstrating the attractiveness of the carrier. Releasing E7,9-10:COOnBu-fed B. cucurbitae (∼2 g pheromone/ha, 1-wk trial duration) resulted in significantly reduced trap catches in treatment fields compared with control fields on the first 2 d of the field trial. Percent disruptions were 84.7% (day 1) and 56.0% (day 2). These results suggest that both conventional communication disruption and mobile communication disruption have potential to control D. pallivitta. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Randomized Controlled Trial of a Web-Delivered Personalized Normative Feedback Intervention to Reduce Alcohol-Related Risky Sexual Behavior among College Students

PubMed Central

Lewis, Melissa A.; Patrick, Megan E.; Litt, Dana. M.; Atkins, David C.; Kim, Theresa; Blayney, Jessica A.; Norris, Jeanette; George, William H.; Larimer, Mary E.

2014-01-01

Objective The purpose of this study was to evaluate the efficacy of personalized normative feedback (PNF) on college student alcohol-related risky sexual behavior (RSB). Method In a randomized controlled trial, 480 (57.6% female) sexually-active college students were stratified by gender and level of drinking and randomly assigned to an alcohol only intervention, an alcohol-related RSB only intervention, a combined alcohol and alcohol-related RSB intervention, or control. All assessment and intervention procedures were web-based. Results Results indicated a significant reduction in drinking outcomes for the alcohol only and the combined alcohol and alcohol-related RSB interventions relative to control. Findings further demonstrated a significant reduction in alcohol-related RSB outcomes for the alcohol-related RSB only and the combined alcohol and alcohol-related RSB interventions relative to control. There were no significant intervention effects on alcohol-related negative consequences. These findings demonstrate that the combined alcohol and alcohol-related RSB intervention was the only intervention successful at reducing both drinking and alcohol-related RSB outcomes relative to control. There were no significant differences when comparing the combined alcohol and alcohol-related RSB intervention to the alcohol only intervention or the alcohol-related RSB only intervention. Finally, results suggested that the intervention effects on high-risk behaviors were mediated by reductions in descriptive normative perceptions. Conclusions These findings demonstrate that PNF specific to drinking in sexual situations was needed to reduce alcohol-related RSB. Furthermore, this study highlights the potential utility of a brief intervention that can be delivered via the Internet to reduce high-risk drinking and alcohol-related RSB among college students. PMID:24491076

Role of the bacterial vaccine Solco-Urovac® in treatment and prevention of recurrent urinary tract infections of bacterial origin.

PubMed

Kochiashvili, D; Khuskivadze, A; Kochiashvili, G; Koberidze, G; Kvakhajelidze, V

2014-06-01

Urinary Tract Infections (UTI) represent a serious medical problem with considerably high rate of morbidity. Recurrent episodes of urinary tract infection (rUTI) may commonly develop in the way of relapse or reinfection. For patients, rUTI is always associated with costs, discomfort and decreased quality of life. Standard treatment of rUTI is through antibiotics and usually such treatment is required repeatedly. Repeat course of antibiotics leads to increase of resistance of uropathogenic strains. According to the European Association of Urology, "the present state of microbial resistance development is alarming". Our post-marketing trial was designed to demonstrate the substantial effect of the bacterial vaccine Solco-Urovac® both with independent administration and in conjunction with standard antibacterial medication within therapy and prevention of rUTI. Total of 115 patients (men and non-pregnant women) were enrolled in our open-label post-marketing trial. Each patient had more than one year history of rUTI and in the past had already taken appropriate course of standard therapy. The trial group included 50 patients: 32 men, 18 women (average age ± 32.5). 32 patients (men) of the trial group received vaccination with Solco-Urovac® together with the standard antibacterial medication. According to bacteriologic tests, in 62% cases infection was caused by Escherichia coli, and in 38% cases by Morganella morganii, Proteus mirabilis, Klebsiella pneumoniae, Enterococcus faecalis. 18 patients within the trial group were women with no recurrence episode at the start and during the trial period. Each woman was involved as the intercourse partner of the respective man within the trial group. The women received only vaccination with Solco-Urovac®. 65 patients of the control group had more than one year history of rUTI and had been treated earlier, too. Patients of the control group received appropriate antibacterial medication without Solco-Urovac®. After therapy and follow-up examination, results in the both groups were classified, also in consideration of the pathogen-specified subgroups, and then summarized and compared respectively. During the follow-up period no case of rUTI was noticed in women. In total, analysis of the medical records of 50 patients of the trial group demonstrated no case of rUTI in 46 patients during the follow-up period. Altogether, the rate of improvement of symptoms was as follows: the trial group - 92%, the control group - 74%. Through comparison with the past medical histories of patients, the higher rate of improvement and longer absence of rUTI episodes after treatment were certainly associated with the effect of Solco-Urovac®. The results of our post-marketing trial allow recommending Solco-Urovac® for appropriate reference within the Georgian National Guideline on Urologic Infections.

Augmenting cognitive processing therapy to improve sleep impairment in PTSD: A randomized controlled trial.

PubMed

Galovski, Tara E; Harik, Juliette M; Blain, Leah M; Elwood, Lisa; Gloth, Chelsea; Fletcher, Thomas D

2016-02-01

Despite the success of empirically supported treatments for posttraumatic stress disorder (PTSD), sleep impairment frequently remains refractory after treatment. This single-site, randomized controlled trial examined the effectiveness of sleep-directed hypnosis as a complement to an empirically supported psychotherapy for PTSD (cognitive processing therapy [CPT]). Participants completed either 3 weeks of hypnosis (n = 52) or a symptom monitoring control condition (n = 56) before beginning standard CPT. Multilevel modeling was used to investigate differential patterns of change to determine whether hypnosis resulted in improvements in sleep, PTSD, and depression. An intervening variable approach was then used to determine whether improvements in sleep achieved during hypnosis augmented change in PTSD and depression during CPT. After the initial phase of treatment (hypnosis or symptom monitoring), the hypnosis condition showed significantly greater improvement than the control condition in sleep and depression, but not PTSD. After CPT, both conditions demonstrated significant improvement in sleep and PTSD; however, the hypnosis condition demonstrated greater improvement in depressive symptoms. As sleep improved, there were corresponding improvements in PTSD and depression, with a stronger relationship between sleep and PTSD. Hypnosis was effective in improving sleep impairment, but those improvements did not augment gains in PTSD recovery during the trauma-focused intervention. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Retention of Implicit Sequence Learning in Persons who Stutter and Persons with Parkinson's Disease

PubMed Central

Smits-Bandstra, Sarah; Gracco, Vincent

2014-01-01

This study investigated the retention of implicit sequence learning in 14 persons with Parkinson's disease (PPD), 14 persons who stutter (PWS) and 14 control participants. Participants completed a nonsense syllable serial reaction time task in a 120-minute session. Participants named aloud four syllables in response to four visual stimuli. The syllables formed a repeating 8-item sequence not made known to participants. After one week, participants completed a 60-minute retention session that included an explicit learning questionnaire and a sequence generation task. PPD showed retention of general learning equivalent to controls but PWS's reaction times were significantly slower on early trials of the retention test relative to other groups. Controls showed implicit learning during the initial session that was retained on the retention test. In contrast, PPD and PWS did not demonstrate significant implicit learning until the retention test suggesting intact, but delayed, learning and retention of implicit sequencing skills. All groups demonstrated similar limited explicit sequence knowledge. Performance differences between PWS and PPD relative to controls during the initial session and on early retention trials indicated possible dysfunction of the cortico-striato-thalamo-cortical loop. The etiological implications for stuttering, and clinical implications for both populations, of this dysfunction are discussed. PMID:23844763

Randomized Controlled Pilot Trial of Mindfulness Training for Stress Reduction during Pregnancy

PubMed Central

Guardino, Christine M.; Dunkel Schetter, Christine; Bower, Julienne E.; Lu, Michael C.; Smalley, Susan L.

2014-01-01

This randomized controlled pilot trial tested a 6-week mindfulness-based intervention in a sample of pregnant women experiencing high levels of perceived stress and pregnancy anxiety. Forty-seven women enrolled between 10 and 25 weeks gestation were randomly assigned to either a series of weekly Mindful Awareness Practices (MAPS) classes (n = 24) with home practice or to a reading control condition (n = 23). Hierarchical linear models of between-group differences in change over time demonstrated that participants in the mindfulness intervention experienced larger decreases from pre-to post-intervention in pregnancy-specific anxiety and pregnancy-related anxiety than participants in the reading control condition. However, these effects were not sustained through follow-up at six weeks post-intervention. Participants in both groups experienced increased mindfulness, as well as decreased perceived stress and state anxiety over the course of the intervention and follow-up periods. This study is one of the first randomized controlled pilot trials of a mindfulness meditation intervention during pregnancy and provides some evidence that mindfulness training during pregnancy may effectively reduce pregnancy-related anxiety and worry. We discuss some of the dilemmas in pursuing this translational strategy and offer suggestions for researchers interested in conducting mind-body interventions during pregnancy. PMID:24180264

Effects of directed written disclosure on grief and distress symptoms among bereaved individuals.

PubMed

Lichtenthal, Wendy G; Cruess, Dean G

2010-07-01

Bereavement-specific written disclosure trials have generally demonstrated null effects, but these studies have not directed the focus of writing. This randomized controlled trial compared directed writing that focused on either sense-making or benefit-finding, both associated with adjustment to loss, to traditional, non-directed emotional disclosure and a control condition. Bereaved undergraduates (n = 68) completed three 20-min writing sessions over 1 week. Intervention effects were found on prolonged grief disorder, depressive, and posttraumatic stress symptoms 3 months postintervention, and the benefit-finding condition appeared particularly efficacious. Physical health improved over time in all treatment groups. Findings suggested that directing written disclosure on topics associated with adjustment to bereavement may be useful for grieving individuals.

EFFECTS OF DIRECTED WRITTEN DISCLOSURE ON GRIEF AND DISTRESS SYMPTOMS AMONG BEREAVED INDIVIDUALS

PubMed Central

LICHTENTHAL, WENDY G.; CRUESS, DEAN G.

2013-01-01

Bereavement-specific written disclosure trials have generally demonstrated null effects, but these studies have not directed the focus of writing. This randomized controlled trial compared directed writing that focused on either sense-making or benefit-finding, both associated with adjustment to loss, to traditional, non-directed emotional disclosure and a control condition. Bereaved undergraduates (n = 68) completed three 20-min writing sessions over 1 week. Intervention effects were found on prolonged grief disorder, depressive, and posttraumatic stress symptoms 3 months postintervention, and the benefit-finding condition appeared particularly efficacious. Physical health improved over time in all treatment groups. Findings suggested that directing written disclosure on topics associated with adjustment to bereavement may be useful for grieving individuals. PMID:24482856

The challenge of establishing treatment efficacy for cutaneous vascular manifestations of systemic sclerosis.

PubMed

Pauling, John D

2018-05-01

The cutaneous vascular manifestations of systemic sclerosis (SSc) comprise Raynaud's phenomenon, cutaneous ulceration, telangiectasia formation and critical digital ischaemia; each of which are associated with significant disease-related morbidity. Despite the availability of multiple classes of vasodilator therapy, many of which have been the subject of RCTs, a limited number of pharmacological interventions are currently approved for the management of cutaneous vascular manifestations of SSc. Areas covered: A major challenge has been demonstrating treatment efficacy with examples of promising therapies yielding contrasting results in controlled trial settings. Differences between consensus best-practice guidelines, evidence-based recommendations and marketing approvals in different jurisdictions has resulted in geographic variation in clinical practice concerning the management of cutaneous vascular manifestations of SSc. Difficulty demonstrating treatment efficacy risks waning industry engagement for drug development programmes in this field. This article highlights the key challenges in establishing treatment efficacy and barriers that must be overcome to support successful clinical trial programmes across the spectrum of cutaneous vascular manifestations of SSc. Expert commentary: The paucity of approved treatments for cutaneous vascular manifestations of SSc relates as much to challenges in clinical trial design and the need for reliable clinical trial endpoints, as to lack of therapeutic options.

Deferasirox: a review of its use for chronic iron overload in patients with non-transfusion-dependent thalassaemia.

PubMed

Shirley, Matt; Plosker, Greg L

2014-06-01

Deferasirox (Exjade(®)) is a once-daily orally administered iron chelator which has been approved for use in the treatment of transfusional-dependent chronic iron overload since 2005. Based primarily on the findings of the THALASSA (Assessment of Exjade(®) in Non-Transfusion-Dependent THALASSemiA) trial, the approval for deferasirox has recently been expanded to include the management of chronic iron overload in patients with non-transfusion-dependent thalassaemia (NTDT) syndromes. Despite the lack of regular blood transfusions, NTDT patients can still develop clinically relevant iron overload, primarily due to increased gastrointestinal absorption secondary to ineffective erythropoiesis, and may require chelation therapy. The THALASSA trial, the first placebo-controlled clinical trial of an iron chelator in NTDT patients, demonstrated that deferasirox was effective in reducing liver iron and serum ferritin levels in this population. Deferasirox has an acceptable tolerability profile, with the most common adverse events reported in the THALASSA trial being related to mild to moderate gastrointestinal disorders. Although further long-term studies will be required to clearly demonstrate the clinical benefit of chelation therapy in NTDT patients, deferasirox presents a useful tool in the management of iron overload in this population.

Methylphenidate blocks effort-induced depletion of regulatory control in healthy volunteers.

PubMed

Sripada, Chandra; Kessler, Daniel; Jonides, John

2014-06-01

A recent wave of studies--more than 100 conducted over the last decade--has shown that exerting effort at controlling impulses or behavioral tendencies leaves a person depleted and less able to engage in subsequent rounds of regulation. Regulatory depletion is thought to play an important role in everyday problems (e.g., excessive spending, overeating) as well as psychiatric conditions, but its neurophysiological basis is poorly understood. Using a placebo-controlled, double-blind design, we demonstrated that the psychostimulant methylphenidate (commonly known as Ritalin), a catecholamine reuptake blocker that increases dopamine and norepinephrine at the synaptic cleft, fully blocks effort-induced depletion of regulatory control. Spectral analysis of trial-by-trial reaction times revealed specificity of methylphenidate effects on regulatory depletion in the slow-4 frequency band. This band is associated with the operation of resting-state brain networks that produce mind wandering, which raises potential connections between our results and recent brain-network-based models of control over attention. © The Author(s) 2014.

Reporting of symptoms in randomized controlled trials of atopic eczema treatments: a systematic review.

PubMed

Gerbens, L A A; Chalmers, J R; Rogers, N K; Nankervis, H; Spuls, P I

2016-10-01

'Symptoms' is a core outcome domain for atopic eczema (AE) trials, agreed by consensus as part of the Harmonising Outcome Measures for Eczema (HOME) initiative. To standardize and validate the core domain symptoms and symptom instruments for AE trials the HOME roadmap is followed. Its first step is to establish if and how symptoms have been measured in published AE treatment trials. Therefore the Global Resource for Eczema Trials database was used to collect all randomized controlled trials (RCTs) of treatments for AE between January 2000 and April 2014. Study selection and data extraction were performed by three reviewers independently. We identified the use of symptoms in 295 of 378 trials (78%). Symptoms as a primary end point were applied by 147 RCTs (50%). Seventeen different symptoms were measured, but mostly itch and sleep loss. Symptoms were assessed by only 37% of trials by a stand-alone symptom measurement. Overall 63% of RCTs used a composite instrument, and 30 different instruments were identified. The Scoring Atopic Dermatitis (SCORAD) index was the most commonly applied, but only 23% of RCTs reported the SCORAD symptom score separately. This systematic review demonstrates that symptoms, most frequently itch and sleep loss, are commonly reported in AE treatment trials, but are measured using many different instruments. Often symptoms are evaluated as part of a composite instrument, and currently it is not possible to extract symptoms-only data from most published studies. Future trials should report symptom scores to permit meta-analysis of the core outcomes. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Intergenerational volunteering and quality of life: mixed methods evaluation of a randomized control trial involving persons with mild to moderate dementia.

PubMed

George, Daniel R

2011-09-01

This article reports on a mixed methods evaluation of a randomized control trial in Cleveland, Ohio, USA, that assessed whether an intergenerational volunteering intervention could enhance quality of life (QOL) for persons with mild to moderate dementia. Fifteen participants were randomized into intervention and control groups. The intervention group participated in hour-long volunteer sessions with a kindergarten class and an older elementary class in alternating weeks over a 5-month interval. Psychometric data on cognitive functioning, stress, depression, sense of purpose, and sense of usefulness were collected at baseline and at the close of the intervention, and change scores were computed and analyzed for all variables. Ethnography was carried out through the duration of the study, and narrative interviews were held with participants and caregivers. A modified grounded theory approach was used for qualitative analysis. Quantitative analysis demonstrated a significant decrease in stress for the intervention group. Qualitative analysis identified three main pathways through which intergenerational volunteering affected QOL: perceived health benefits, sense of purpose and sense of usefulness, and relationships. Mixed methods evaluation demonstrated that intergenerational volunteering might enhance quality of life through several key pathways, most significantly reduced stress.

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

PubMed Central

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

2008-01-01

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

Evaluation of a dental floss containing soluble pyrophosphate on calculus formation using a short-term clinical model.

PubMed

Kleber, C J; Putt, M S; Milleman, J L; Harris, M

1998-01-01

This clinical study compared the effect of a dental floss containing 0.25 mg tetrasodium pyrophosphate per cm and a placebo floss on supragingival calculus formation using a 6-week, partial-mouth toothshield model. The six lower anterior teeth were scaled and polished before each 2-week period (i.e., pre-trial, washout, trial). During both the pre-trial and trial periods, subjects brushed twice daily with a non-tartar control dentifrice, while a toothshield protected the six test teeth from brushing. After rinsing with water and removing the shield, they flossed the test teeth. All subjects used placebo floss during the pre-trial period in order to determine the baseline Volpe-Manhold Index (VMI) calculus formation scores, which were used to balance groups for the trial period. During the trial period, one group used the placebo floss, while the second group used the pyrophosphate floss. The final results demonstrated that the pyrophosphate floss significantly inhibited calculus formation between teeth (mesial-distal scores) by 21%, and on labial surfaces by 37% relative to the placebo floss.

Heated, humidified air for the common cold.

PubMed

Singh, Meenu; Singh, Manvi

2011-05-11

Heated, humidified air has long been used by sufferers of the common cold. The theoretical basis is that steam may help congested mucus drain better and heat may destroy the cold virus as it does in vitro. To assess the effects of inhaling heated water vapour (steam) in the treatment of the common cold by comparing symptoms, viral shedding and nasal resistance. In this updated review we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to July Week 1, 2010), EMBASE (1990 to July 2010) and Current Contents (1994 to July 2010). Randomised controlled trials (RCTs) using heated water vapour in participants with the common cold or participants with experimentally-induced common cold. We reviewed all retrieved articles and excluded any articles, editorials and abstracts with inadequate outcome descriptions. The studies we included were subjected to a methodological assessment. Six trials (394 trial participants) were included. Three trials in which patient data could be pooled found benefits of steam for symptom relief for the common cold (odds ratio (OR) 0.31; 95% confidence interval (CI) 0.16 to 0.60). However, results on symptom indices were equivocal. No studies demonstrated an exacerbation of clinical symptom scores. One study conducted in the USA demonstrated worsened nasal resistance, while an earlier Israeli study showed improvement. One study examined viral shedding and antibody titres in nasal washings; there was no change in either between treatment and placebo groups. Minor side effects (including discomfort or irritation of the nose) were reported in some studies. Steam inhalation has not shown any consistent benefits in the treatment of the common cold, hence is not recommended in the routine treatment of common cold symptoms until more double-blind, randomized trials with a standardised treatment modality are conducted.

Environmental sanitary interventions for preventing active trachoma.

PubMed

Rabiu, M; Alhassan, M; Ejere, H

2007-10-17

Trachoma is a major cause of avoidable blindness. It is responsible for about six million blind people worldwide, mostly in the poor communities of developing countries. One of the major strategies advocated for the control of the disease is the application of various environmental sanitary measures to such communities. To assess the evidence for the effectiveness of environmental sanitary measures on the prevalence of active trachoma in endemic areas. We searched the Cochrane Central Register of Controlled Trials - CENTRAL in The Cochrane Library (Issue 2, 2007), MEDLINE (1966 to July 2007), EMBASE (1980 to July 2007), LILACS (July 2007), reference list of trials and the Science Citation Index. We also contacted agencies, experts and researchers in trachoma control. We included randomised and quasi-randomised controlled trials comparing any form of environmental hygiene measures with no measure. These hygiene measures included fly control, provision of water and health education. Participants in the trials were people normally resident in the trachoma endemic areas. Two authors independently extracted data and assessed the quality of trials. Study authors were contacted for additional information. Four trials met the inclusion criteria but meta-analysis was not conducted due to heterogeneity of the studies. Two studies that assessed insecticide spray as a fly control measure found that trachoma is reduced by at least 55% to 61% with this measure compared to no intervention. However, another study did not find insecticide spray to be effective in reducing trachoma. One study found that another fly control measure, latrine provision, reduced trachoma by 29.5% compared to no intervention; this was, however, not statistically significantly different. Another study revealed that health education on personal and household hygiene reduced the incidence of trachoma such that the odds of reducing trachoma in the health education village was about twice that of the no intervention village. However, all the studies have some methodological concerns relating to concealment of allocation and non-consideration of clustering effect in data analysis. The role of insecticide spray as a fly control measure in reducing trachoma remains unclear. Latrine provision as a fly control measure has not demonstrated significant trachoma reduction. Health education may be effective in reducing trachoma. There is a dearth of data to determine the effectiveness of all aspects of environmental sanitation in the control of trachoma.

Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review.

PubMed

Caroff, Stanley N; Aggarwal, Saurabh; Yonan, Charles

2018-02-01

Up to 30% of patients taking antipsychotics may develop tardive dyskinesia (TD). Recent evidence-based recommendations demonstrate an unmet need for effective TD management. This systematic review was designed to update the evidence for TD treatment, comparing two vesicular monoamine transporter 2 (VMAT2) inhibitors, tetrabenazine and valbenazine. Of 487 PubMed/Embase search results, 11 studies met the review criteria. Valbenazine efficacy was demonstrated in rigorously designed clinical trials that meet the guidelines for AAN Class I evidence. Due to differences in study designs and a lack of standardized and controlled trials with tetrabenazine, a formal meta-analysis comparing the agents was not possible. However, valbenazine appears to have fewer side effects and a more favorable once-daily dosing regimen for the treatment of TD.

Single-Trial Regression Elucidates the Role of Prefrontal Theta Oscillations in Response Conflict

PubMed Central

Cohen, Michael X; Cavanagh, James F.

2011-01-01

In most cognitive neuroscience experiments there are many behavioral and experimental dynamics, and many indices of brain activity, that vary from trial to trial. For example, in studies of response conflict, conflict is usually treated as a binary variable (i.e., response conflict exists or does not in any given trial), whereas some evidence and intuition suggests that conflict may vary in intensity from trial to trial. Here we demonstrate that single-trial multiple regression of time–frequency electrophysiological activity reveals neural mechanisms of cognitive control that are not apparent in cross-trial averages. We also introduce a novel extension to oscillation phase coherence and synchronization analyses, based on “weighted” phase modulation, that has advantages over standard coherence measures in terms of linking electrophysiological dynamics to trial-varying behavior and experimental variables. After replicating previous response conflict findings using trial-averaged data, we extend these findings using single-trial analytic methods to provide novel evidence for the role of medial frontal–lateral prefrontal theta-band synchronization in conflict-induced response time dynamics, including a role for lateral prefrontal theta-band activity in biasing response times according to perceptual conflict. Given that these methods shed new light on the prefrontal mechanisms of response conflict, they are also likely to be useful for investigating other neurocognitive processes. PMID:21713190

Effect of Newborn Resuscitation Training on Health Worker Practices in Pumwani Hospital, Kenya

PubMed Central

Opiyo, Newton; Were, Fred; Govedi, Fridah; Fegan, Greg; Wasunna, Aggrey; English, Mike

2008-01-01

Background Birth asphyxia kills 0.7 to 1.6 million newborns a year globally with 99% of deaths in developing countries. Effective newborn resuscitation could reduce this burden of disease but the training of health-care providers in low income settings is often outdated. Our aim was to determine if a simple one day newborn resuscitation training (NRT) alters health worker resuscitation practices in a public hospital setting in Kenya. Methods/Principal Findings We conducted a randomised, controlled trial with health workers receiving early training with NRT (n = 28) or late training (the control group, n = 55). The training was adapted locally from the approach of the UK Resuscitation Council. The primary outcome was the proportion of appropriate initial resuscitation steps with the frequency of inappropriate practices as a secondary outcome. Data were collected on 97 and 115 resuscitation episodes over 7 weeks after early training in the intervention and control groups respectively. Trained providers demonstrated a higher proportion of adequate initial resuscitation steps compared to the control group (trained 66% vs control 27%; risk ratio 2.45, [95% CI 1.75–3.42], p<0.001, adjusted for clustering). In addition, there was a statistically significant reduction in the frequency of inappropriate and potentially harmful practices per resuscitation in the trained group (trained 0.53 vs control 0.92; mean difference 0.40, [95% CI 0.13–0.66], p = 0.004). Conclusions/Significance Implementation of a simple, one day newborn resuscitation training can be followed immediately by significant improvement in health workers' practices. However, evidence of the effects on long term performance or clinical outcomes can only be established by larger cluster randomised trials. Trial Registration Controlled-Trials.com ISRCTN92218092 PMID:18270586

Effects of Computer-Aided Interlimb Force Coupling Training on Paretic Hand and Arm Motor Control following Chronic Stroke: A Randomized Controlled Trial

PubMed Central

Lin, Chueh-Ho; Chou, Li-Wei; Luo, Hong-Ji; Tsai, Po-Yi; Lieu, Fu-Kong; Chiang, Shang-Lin; Sung, Wen-Hsu

2015-01-01

Objective We investigated the training effects of interlimb force coupling training on paretic upper extremity outcomes in patients with chronic stroke and analyzed the relationship between motor recovery of the paretic hand, arm and functional performances on paretic upper limb. Design A randomized controlled trial with outcome assessment at baseline and after 4 weeks of intervention. Setting Taipei Veterans General Hospital, National Yang-Ming University. Participants Thirty-three subjects with chronic stroke were recruited and randomly assigned to training (n = 16) and control groups (n = 17). Interventions The computer-aided interlimb force coupling training task with visual feedback included different grip force generation methods on both hands. Main Outcome Measures The Barthel Index (BI), the upper extremity motor control Fugl-Meyer Assessment (FMA-UE), the Motor Assessment Score (MAS), and the Wolf Motor Function Test (WMFT). All assessments were executed by a blinded evaluator, and data management and statistical analysis were also conducted by a blinded researcher. Results The training group demonstrated greater improvement on the FMA-UE (p<.001), WMFT (p<.001), MAS (p = .004) and BI (p = .037) than the control group after 4 weeks of intervention. In addition, a moderate correlation was found between the improvement of scores for hand scales of the FMA and other portions of the FMA UE (r = .528, p = .018) or MAS (r = .596, p = .015) in the training group. Conclusion Computer-aided interlimb force coupling training improves the motor recovery of a paretic hand, and facilitates motor control and enhances functional performance in the paretic upper extremity of people with chronic stroke. Trial Registration ClinicalTrials.gov NCT02247674. PMID:26193492

The effects of stereotype threat and contextual cues on alcohol users' inhibitory control.

PubMed

Pennington, Charlotte R; Qureshi, Adam; Monk, Rebecca L; Heim, Derek

2016-03-01

Previous research indicates that users of illicit substances exhibit diminished cognitive function under stereotype threat. Advancing this research, the current study aimed to examine the effects of stereotype threat on alcohol users' inhibitory control. It also examined whether drinkers demonstrate a greater approach bias towards alcohol-related relative to neutral stimuli. Fifty-five participants were assigned randomly to a stereotype threat condition, in which they were primed with a negative stereotype linking drinking behavior to cognitive decline, or a non-threat control condition. All participants then completed a modified version of the Cued Go/No-Go Association Test that exposed participants to alcohol-related and neutral pictorial stimuli and sound cues. Stereotype threatened participants demonstrated a speed-accuracy trade off, taking significantly longer to respond to go-trials with equivalent accuracy to the control condition. They also showed reduced response accuracy to both alcohol-related and neutral stimuli in reversed instruction trials. Participants in the control condition were both more accurate and quicker to respond to alcohol-related stimuli compared to neutral stimuli. These results suggest that awareness of negative stereotypes pertaining to alcohol-related impulsivity may have a harmful effect on inhibitive cognitive performance. This may have implications for public health campaigns and for methodological designs with high levels of procedural signaling with respect to not inadvertently inducing stereotype threat and impacting impulsivity. Copyright © 2015 Elsevier Ltd. All rights reserved.

A comprehensive evaluation of the impact of telemonitoring in patients with long-term conditions and social care needs: protocol for the whole systems demonstrator cluster randomised trial

PubMed Central

2011-01-01

Background It is expected that increased demands on services will result from expanding numbers of older people with long-term conditions and social care needs. There is significant interest in the potential for technology to reduce utilisation of health services in these patient populations, including telecare (the remote, automatic and passive monitoring of changes in an individual's condition or lifestyle) and telehealth (the remote exchange of data between a patient and health care professional). The potential of telehealth and telecare technology to improve care and reduce costs is limited by a lack of rigorous evidence of actual impact. Methods/Design We are conducting a large scale, multi-site study of the implementation, impact and acceptability of these new technologies. A major part of the evaluation is a cluster-randomised controlled trial of telehealth and telecare versus usual care in patients with long-term conditions or social care needs. The trial involves a number of outcomes, including health care utilisation and quality of life. We describe the broad evaluation and the methods of the cluster randomised trial Discussion If telehealth and telecare technology proves effective, it will provide additional options for health services worldwide to deliver care for populations with high levels of need. Trial Registration Current Controlled Trials ISRCTN43002091 PMID:21819569

Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.

PubMed

Poewe, Werner; Mahlknecht, Philipp; Krismer, Florian

2015-09-15

Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.

Fibrin Sealants in Dura Sealing: A Systematic Literature Review

PubMed Central

2016-01-01

Background Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. Methods A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. Results A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. Conclusions A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety. PMID:27119993

Fibrin Sealants in Dura Sealing: A Systematic Literature Review.

PubMed

Esposito, Felice; Angileri, Filippo Flavio; Kruse, Peter; Cavallo, Luigi Maria; Solari, Domenico; Esposito, Vincenzo; Tomasello, Francesco; Cappabianca, Paolo

2016-01-01

Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or powered to demonstrate a significant advantage to fibrin sealant use. Two small case series studies evaluated the effect of fibrin sealants in persistent cerebrospinal fluid leak treatment, but did not establish firm efficacy conclusions. Specific adverse reports where fibrin sealants were used for dura sealing were limited, with only 8 cases reported in neurosurgical procedures since 1987 and most reporting only a speculative relationship/association with fibrin sealant exposure. A major finding of this systematic literature review is that there is a paucity of randomized studies that have evaluated the effectiveness and safety of fibrin sealants in providing intraoperative watertight dura closure and post-operative cerebrospinal fluid leakage. Among the limited studies available, evidence from a single randomized, controlled trial indicates that fibrin sealants provide a higher rate of intraoperative watertight closure of the dura suture line than control, albeit with a higher rate of postoperative cerebrospinal fluid leakage. Evidence from non-randomized, controlled trials suggests that fibrin sealants may be effective in preventing cerebrospinal fluid leaks with an acceptable safety profile. There is a substantial need for randomized, controlled clinical trials or well-designed prospective observational trials where the conduct of a randomized trial is not feasible to fully assess the impact of fibrin sealant utilization on the rates of intraoperative dura closure, postoperative cerebrospinal leakage, and safety.

Selenium and glutamine supplements: where are we heading? A critical care perspective.

PubMed

Andrews, Peter J D

2010-03-01

There is considerable interest in glutamine and selenium in critical care as both offer the potential to enhance host defences, through different but complimentary mechanisms and may reduce subsequent infections and mortality. The SIGNET trial (randomized controlled factorial trial) is the largest, critical care study of both supplements. The data have been presented publicly, but the data are not published or available for review and will therefore not be discussed fully in this update. In the present review I will explore the recently available (past 1-2 years) published literature. The current literature demonstrates that there are currently insufficient data to enable confident recommendations on the optimal route, timing, duration and dosage of each of these nutritional supplements. The pending results of SIGNET, the largest critical care trial of parenteral nutrition supplemented by glutamine and or selenium promises to clarify some of the current ambiguities and inform future practice. To be able to confidently establish or refute the hypothesis that either glutamine or selenium alone or in combination improves outcome in critical care requires a well designed prospective randomized controlled trial. To design such a trial we require the optimal dose and duration of the nutritional supplement (balancing efficacy and toxicity, ease of administration and cost) and then conduct an adequately powered trial. Such a trial is still lacking for these two agents. There are some supportive data for selenium but the case is less strong for parenteral glutamine and weakest for enteral glutamine.

The analgesic effect of wound infiltration with local anaesthetics after breast surgery: a qualitative systematic review.

PubMed

Byager, N; Hansen, M S; Mathiesen, O; Dahl, J B

2014-04-01

Wound infiltration with local anaesthetics is commonly used during breast surgery in an attempt to reduce post-operative pain and opioid consumption. The aim of this review was to evaluate the effect of wound infiltration with local anaesthetics compared with a control group on post-operative pain after breast surgery. A systematic review was performed by searching PubMed, Google Scholar, the Cochrane database and Embase for randomised, blinded, controlled trials of wound infiltration with local anaesthetics for post-operative pain relief in female adults undergoing breast surgery. The analgesic effect was evaluated in a qualitative analysis by assessment of significant difference between groups (P < 0.05) in pain scores and supplemental analgesic consumption. Ten trials including 699 patients were included in the final analysis. Three trials investigated mastectomy, four trials partial or segmental mastectomy, and three trials breast reduction, excision of benign lump and unspecified breast surgery, respectively. Six trials demonstrated a small and short-lasting, but statistically significant reduction of post-operative pain scores, and four trials observed a statistically significant reduction in post-operative, supplemental opioid consumption that was, however, of limited clinical relevance. Wound infiltration with local anaesthetics may have a modest analgesic effect in the first few hours after surgery. Pain after breast surgery is, however, generally mild to moderate, and other non-invasive analgesic methods may be preferable in this surgical population. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis.

PubMed

McPherson, Stuart; Wilkinson, Nina; Tiniakos, Dina; Wilkinson, Jennifer; Burt, Alastair D; McColl, Elaine; Stocken, Deborah D; Steen, Nick; Barnes, Jane; Goudie, Nicola; Stewart, Stephen; Bury, Yvonne; Mann, Derek; Anstee, Quentin M; Day, Christopher P

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. Experimental and small clinical trials have demonstrated that angiotensin II blockers (ARB) may be anti-fibrotic in the liver. The aim of this randomised controlled trial was to assess whether treatment with Losartan for 96 weeks slowed, halted or reversed the progression of fibrosis in patients with non-alcoholic steatohepatitis (NASH). Double-blind randomised-controlled trial of Losartan 50 mg once a day versus placebo for 96 weeks in patients with histological evidence of NASH. The primary outcome for the study was change in histological fibrosis stage from pre-treatment to end-of-treatment. The study planned to recruit 214 patients. However, recruitment was slower than expected, and after 45 patients were randomised (median age 55; 56% male; 60% diabetic; median fibrosis stage 2), enrolment was suspended. Thirty-two patients (15 losartan and 17 placebo) completed follow up period: one patient (6.7%) treated with losartan and 4 patients (23.5%) in the placebo group were "responders" (lower fibrosis stage at follow up compared with baseline). The major reason for slow recruitment was that 39% of potentially eligible patients were already taking an ARB or angiotensin converting enzyme inhibitor (ACEI), and 15% were taking other prohibited medications. Due to the widespread use of ACEI and ARB in patients with NASH this trial failed to recruit sufficient patients to determine whether losartan has anti-fibrotic effects in the liver. ISRCTN 57849521.

[JUSTIFICATION OF USING EQUIVALENCE OF THE INDICES OF QUALITY, SAFETY, AND EFFICACY IN DEVELOPING BIOANALOGS].

PubMed

Niyazov, R R; Goryachev, D V; Gavrishina, E V; Romodanovskii, D P; Dranitsyna, M A

2015-01-01

We describe general principles of demonstrating biosimilarity, as well as selecting the biosimilarity margins. Any change in the structure of a biological molecule can modify its functional activity. Therefore, therapeutic equivalence between a biosimilar product and the corresponding reference product cannot be demonstrated using a single criterion. To demonstrate biosimilarity between two medicinal products, their various characteristics have to be evaluated which may, directly or indirectly, justify that clinically significant differences are absent. Insufficient understanding of 6ritical quality attributes brings a risk for the biosimilar product developer. This will either increase the number of non-clinical and clinical tests and trials needed or will result in awareness that the manufacturing process needs to be improved at the late stages of development, after investing significant resources in the development process. At the same time, the specification of the biological medicinal product cannot solely ensure safety and efficacy thereof. Properly characterized and controlled manufacturing process, which ensures consistency in its attributes not adequately controlled in specifications but influencing safety and efficacy profiles and showing their relevance in non-clinical tests and clinical trials, is an additional quality assurance factor. Justification of all development strategy details, including biosimilarity margins, has to be provided each time when the development process is initiated or when proceeding to the next steps. All problems encountered by the developer have to be resolved in close communication with the regulatory authority. In order to increase the quality of investigation and developer's adherence to good practices, clinical trial results should be published in detail.

Evidence-based dentistry: a model for clinical practice.

PubMed

Faggion, Clóvis M; Tu, Yu-Kang

2007-06-01

Making decisions in dentistry should be based on the best evidence available. The objective of this study was to demonstrate a practical procedure and model that clinicians can use to apply the results of well-conducted studies to patient care by critically appraising the evidence with checklists and letter grade scales. To demonstrate application of this model for critically appraising the quality of research evidence, a hypothetical case involving an adult male with chronic periodontitis is used as an example. To determine the best clinical approach for this patient, a four-step, evidence-based model is demonstrated, consisting of the following: definition of a research question using the PICO format, search and selection of relevant literature, critical appraisal of identified research reports using checklists, and the application of evidence. In this model, the quality of research evidence was assessed quantitatively based on different levels of quality that are assigned letter grades of A, B, and C by evaluating the studies against the QUOROM (Quality of Reporting Meta-Analyses) and CONSORT (Consolidated Standards of Reporting Trials) checklists in a tabular format. For this hypothetical periodontics case, application of the model identified the best available evidence for clinical decision making, i.e., one randomized controlled trial and one systematic review of randomized controlled trials. Both studies showed similar answers for the research question. The use of a letter grade scale allowed an objective analysis of the quality of evidence. A checklist-driven model that assesses and applies evidence to dental practice may substantially improve dentists' decision making skill.

Mindfulness interventions for psychosis: a systematic review of the literature.

PubMed

Aust, J; Bradshaw, T

2017-02-01

WHAT IS KNOWN ON THE SUBJECT?: Psychosis and the more specific diagnosis of schizophrenia constitute a major psychiatric disorder which impacts heavily on the self-esteem, functioning and quality of life of those affected. A number of mindfulness therapies have been developed in recent years, showing promising results when used with people with the disorder. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This review of the literature included only randomized controlled trials (RCTs), rather than other typically less robust methods of research (e.g. case studies, noncontrolled studies). WHAT ARE THE IMPLICATIONS FOR PRACTICE?: We concluded that mindfulness therapies can be safely used with people with psychosis and that they provide a number of therapeutic benefits compared with routine care and, in some cases, other interventions. Larger, methodologically improved trials are now recommended to evaluate the benefits of mindfulness therapies further. Introduction A growing number of mindfulness interventions are being used with individuals with psychosis. These therapies employ elements of acceptance and compassion in addition to mindfulness. A number of randomized controlled trials (RCTs) of these interventions have emerged in recent years, but no review of these latest trials exists. Question 'For individuals with psychosis, are mindfulness interventions more effective than treatment as usual or an alternative intervention, in improving patient-related outcomes as demonstrated in RCTs?' Method We undertook a systematic review of randomized controlled studies of mindfulness interventions for psychosis and schizophrenia (MIps). Studies were identified by searching the databases Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and Allied and Complementary Medicine. Findings The review identified 11 RCTs investigating eight mindfulness interventions. Significant improvements were reported on a number of measures, although gains were mostly smaller in trials employing well-designed controls and where assessors were blind to treatment allocation. There was considerable heterogeneity amongst trials in the diversity of treatments reviewed and the range of outcomes assessed. Implications for Practice The findings suggest MIps are feasible for individuals with psychosis and provide a number of significant benefits over routine care and, in some cases, other interventions. © 2016 John Wiley & Sons Ltd.

Dronedarone: current evidence and future questions.

PubMed

Schafer, Jeremy A; Kjesbo, Nicole K; Gleason, Patrick P

2010-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting more than 2.2 million Americans. ACC/AHA/ESC guidelines for the management of patients with AF recommend amiodarone for maintaining sinus rhythm. Dronedarone is a derivative of amiodarone indicated for the treatment of AF. To provide an overview of dronedarone with a focus on the phase III trials and discuss unresolved questions of dronedarone. A literature search was conducted via the PubMed database using the keyword "dronedarone." Search was limited to human trials in english. The FDA website was searched for briefing documents and subcommittee meetings on dronedarone. Clinicaltrials.gov was searched with the keyword dronedarone for upcoming or unpublished clinical trials. Five phase III trials are available for dronedarone: ANDROMEDA, EURIDIS/ADONIS, ATHENA, ERATO, and DIONYSIS. EURIDIS/ADONIS and ATHENA demonstrated a reduction AF recurrence with dronedarone compared to placebo. The ANDROMEDA trial recruited patients with recent hospitalization for heart failure and was terminated due to an excess of deaths in the dronedarone group. The DIONYSIS trial was a comparative effectiveness trial that demonstrated less efficacy for dronedarone but improved tolerability compared to amiodarone. Dronedarone represents an option in the management of AF in select patients. Dronedarone is not appropriate in patients with recently decompensated heart failure or those treated with strong CYP3A4 inhibitors or medications prolonging the QT interval. Dronedarone appears to have improved tolerability at the expense of decreased efficacy when compared to amiodarone. Questions remain on the long-term safety, use in patients with heart failure, retreatment after dronedarone or amiodarone failure, and comparative efficacy with a rate control strategy.

Couple-Focused Prevention at the Transition to Parenthood, a Randomized Trial: Effects on Coparenting, Parenting, Family Violence, and Parent and Child Adjustment.

PubMed

Feinberg, Mark E; Jones, Damon E; Hostetler, Michelle L; Roettger, Michael E; Paul, Ian M; Ehrenthal, Deborah B

2016-08-01

The transition to parenthood is a stressful period for most parents as individuals and as couples, with variability in parent mental health and couple relationship functioning linked to children's long-term emotional, mental health, and academic outcomes. Few couple-focused prevention programs targeting this period have been shown to be effective. The purpose of this study was to test the short-term efficacy of a brief, universal, transition-to-parenthood intervention (Family Foundations) and report the results of this randomized trial at 10 months postpartum. This was a randomized controlled trial; 399 couples expecting their first child were randomly assigned to intervention or control conditions after pretest. Intervention couples received a manualized nine-session (five prenatal and four postnatal classes) psychoeducational program delivered in small groups. Intent-to-treat analyses indicated that intervention couples demonstrated better posttest levels than control couples on more than two thirds of measures of coparenting, parent mental health, parenting, child adjustment, and family violence. Program effects on family violence were particularly large. Of eight outcome variables that did not demonstrate main effects, seven showed moderated intervention impact; such that, intervention couples at higher levels of risk during pregnancy showed better outcomes than control couples at similar levels of risk. These findings replicate a prior smaller study of Family Foundations, indicating that the Family Foundations approach to supporting couples making the transition to parenthood can have broad impact for parents, family relationships, and children's adjustment. Program effects are consistent and benefit all families, with particularly notable effects for families at elevated prenatal risk.

An Approach to Assess Generalizability in Comparative Effectiveness Research: A Case Study of the Whole Systems Demonstrator Cluster Randomized Trial Comparing Telehealth with Usual Care for Patients with Chronic Health Conditions.

PubMed

Steventon, Adam; Grieve, Richard; Bardsley, Martin

2015-11-01

Policy makers require estimates of comparative effectiveness that apply to the population of interest, but there has been little research on quantitative approaches to assess and extend the generalizability of randomized controlled trial (RCT)-based evaluations. We illustrate an approach using observational data. Our example is the Whole Systems Demonstrator (WSD) trial, in which 3230 adults with chronic conditions were assigned to receive telehealth or usual care. First, we used novel placebo tests to assess whether outcomes were similar between the RCT control group and a matched subset of nonparticipants who received usual care. We matched on 65 baseline variables obtained from the electronic medical record. Second, we conducted sensitivity analysis to consider whether the estimates of treatment effectiveness were robust to alternative assumptions about whether "usual care" is defined by the RCT control group or nonparticipants. Thus, we provided alternative estimates of comparative effectiveness by contrasting the outcomes of the RCT telehealth group and matched nonparticipants. For some endpoints, such as the number of outpatient attendances, the placebo tests passed, and the effectiveness estimates were robust to the choice of comparison group. However, for other endpoints, such as emergency admissions, the placebo tests failed and the estimates of treatment effect differed markedly according to whether telehealth patients were compared with RCT controls or matched nonparticipants. The proposed placebo tests indicate those cases when estimates from RCTs do not generalize to routine clinical practice and motivate complementary estimates of comparative effectiveness that use observational data. Future RCTs are recommended to incorporate these placebo tests and the accompanying sensitivity analyses to enhance their relevance to policy making. © The Author(s) 2015.

The Effect of Endothelin Receptor Antagonists in Patients with Eisenmenger Syndrome: A Systematic Review.

PubMed

Elshafay, Abdelrahman; Truong, Duy Hieu; AboElnas, Mohamed M; Idrees, Hossam; Metwali, Hatem G; Vuong, Nguyen Lam; Saad, Omar Ahmed; Hirayama, Kenji; Huy, Nguyen Tien

2018-04-01

The efficacy of endothelin receptor antagonists (ERAs) in the management of Eisenmenger syndrome (ES) remains controversial. The aim of this study is to systemically review the safety and effects of ERAs in improving the quality of life and basic cardiac functions of these patients. Twelve databases were searched, including PubMed, Web of Science, Scopus, Virtual Health Library, World Health Organization (WHO) Global Health Library, Google Scholar, POPLINE, Systems for Information of Grey Literature in Europe, New York Academy of Medicine, ClinicalTrials.gov, metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform, through August 2016. We included randomized clinical trials addressing the effect of ERAs on cardiac functions in patients with ES. The quality of studies was assessed using the Cochrane Collaboration tool. We included two trials represented by four papers, of which three papers reported the efficacy of bosentan against placebo and one paper reported the results of a combination of bosentan and sildenafil versus placebo and bosentan. One trial showed a significant effect of bosentan treatment over placebo on indexed pulmonary vascular resistance and mean pulmonary artery pressure, but a non-significant increase in 6-min walk distance and a non-significant effect on systemic pulse oximetry. The other trial reported the safe but non-significant effect of combination therapy of bosentan and sildenafil compared with bosentan and placebo. This study demonstrated safety and improved hemodynamic effects of bosentan in ES, with a controversial effect on exercise capacity. Further randomized controlled trials with longer follow-up duration are needed to confirm these results.

Implementation and results of an integrated data quality assurance protocol in a randomized controlled trial in Uttar Pradesh, India.

PubMed

Gass, Jonathon D; Misra, Anamika; Yadav, Mahendra Nath Singh; Sana, Fatima; Singh, Chetna; Mankar, Anup; Neal, Brandon J; Fisher-Bowman, Jennifer; Maisonneuve, Jenny; Delaney, Megan Marx; Kumar, Krishan; Singh, Vinay Pratap; Sharma, Narender; Gawande, Atul; Semrau, Katherine; Hirschhorn, Lisa R

2017-09-07

There are few published standards or methodological guidelines for integrating Data Quality Assurance (DQA) protocols into large-scale health systems research trials, especially in resource-limited settings. The BetterBirth Trial is a matched-pair, cluster-randomized controlled trial (RCT) of the BetterBirth Program, which seeks to improve quality of facility-based deliveries and reduce 7-day maternal and neonatal mortality and maternal morbidity in Uttar Pradesh, India. In the trial, over 6300 deliveries were observed and over 153,000 mother-baby pairs across 120 study sites were followed to assess health outcomes. We designed and implemented a robust and integrated DQA system to sustain high-quality data throughout the trial. We designed the Data Quality Monitoring and Improvement System (DQMIS) to reinforce six dimensions of data quality: accuracy, reliability, timeliness, completeness, precision, and integrity. The DQMIS was comprised of five functional components: 1) a monitoring and evaluation team to support the system; 2) a DQA protocol, including data collection audits and targets, rapid data feedback, and supportive supervision; 3) training; 4) standard operating procedures for data collection; and 5) an electronic data collection and reporting system. Routine audits by supervisors included double data entry, simultaneous delivery observations, and review of recorded calls to patients. Data feedback reports identified errors automatically, facilitating supportive supervision through a continuous quality improvement model. The five functional components of the DQMIS successfully reinforced data reliability, timeliness, completeness, precision, and integrity. The DQMIS also resulted in 98.33% accuracy across all data collection activities in the trial. All data collection activities demonstrated improvement in accuracy throughout implementation. Data collectors demonstrated a statistically significant (p = 0.0004) increase in accuracy throughout consecutive audits. The DQMIS was successful, despite an increase from 20 to 130 data collectors. In the absence of widely disseminated data quality methods and standards for large RCT interventions in limited-resource settings, we developed an integrated DQA system, combining auditing, rapid data feedback, and supportive supervision, which ensured high-quality data and could serve as a model for future health systems research trials. Future efforts should focus on standardization of DQA processes for health systems research. ClinicalTrials.gov identifier, NCT02148952 . Registered on 13 February 2014.

Failures in Phase III: Causes and Consequences.

PubMed

Seruga, Bostjan; Ocana, Alberto; Amir, Eitan; Tannock, Ian F

2015-10-15

Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients. ©2015 American Association for Cancer Research.

Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study—a randomised controlled trial

PubMed Central

Frith, Peter A; Thompson, Philip J; Ratnavadivel, Rajeev; Chang, Catherina L; Bremner, Peter; Day, Peter; Frenzel, Christina; Kurstjens, Nicol

2015-01-01

Background The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Methods This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. Results 773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. Conclusions GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP. Trial registration number NCT01513460. PMID:25841237

Post-trial dopaminergic modulation of conditioned catalepsy: A single apomorphine induced increase/decrease in dopaminergic activation immediately following a conditioned catalepsy response can reverse/enhance a haloperidol conditioned and sensitized catalepsy response.

PubMed

Oliveira, Lucas Rangel; Dias, Flávia Regina Cruz; Santos, Breno Garone; Silva, Jade Leal Loureiro; Carey, Robert J; Carrera, Marinete Pinheiro

2016-09-15

Haloperidol can induce catalepsy and this drug effect can be conditioned as well as sensitized to contextual cues. We used a paired/unpaired Pavlovian conditioning protocol to establish haloperidol catalepsy conditioned and sensitized responses. Groups of rats were given 10 daily catalepsy tests following administration of vehicle (n=24) or haloperidol (1.0mg/kg) either paired (n=18) or unpaired (n=18) to testing. Subsequently, testing for conditioning was conducted and conditioning and sensitization of catalepsy were observed selectively in the paired group. Immediately following a second test for catalepsy conditioning, the groups were subdivided into 4 vehicle groups, 3 unpaired haloperidol groups and 3 paired haloperidol groups and were given one of three post-trial treatments (vehicle, 0.05mg/kg or 2.0mg/kg apomorphine). One day later the conditioned catalepsy test 3 was carried out and on the next day, a haloperidol challenge test was performed. The post-trial apomorphine treatments had major effects on the paired groups upon both conditioning and the haloperidol challenge test. The low dose apomorphine post-trial treatment enhanced both the conditioned and the haloperidol sensitized catalepsy responses. The high dose apomorphine post-trial treatment eliminated conditioned catalepsy and eliminated the initial acute catalepsy response to haloperidol that was induced in the vehicle control groups. These results demonstrate the sensitivity of conditioned drug cues to modification by increases/decreases in activity of the dopamine system in the immediate post-trial interval after a conditioning trial. This demonstration that post-trial dopaminergic drug treatments can modify conditioned drug behavior has broad implications for conditioned drug effects. Copyright © 2016 Elsevier B.V. All rights reserved.

A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders.

PubMed

Minshawi, Noha F; Wink, Logan K; Shaffer, Rebecca; Plawecki, Martin H; Posey, David J; Liu, Hai; Hurwitz, Sarah; McDougle, Christopher J; Swiezy, Naomi B; Erickson, Craig A

2016-01-01

Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio. No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. ClinicalTrials.govNCT01086475.

Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results.

PubMed

Aggarwal, Sunil K

2013-02-01

This article attempts to cover pragmatic clinical considerations involved in the use of cannabinergic medicines in pain practice, including geographical and historical considerations, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, indications, and contraindications. Topics include molecular considerations such as the 10-fold greater abundance of cannabinoid type 1 receptors compared to µ-opioid receptors in the central nervous system and anatomic distributions of cannabinoid receptors in pain circuits. The article uses a narrative review methodology drawing from authoritative textbooks and journals of cannabinoid medicine, Food and Drug Administration-approved cannabinoid drug labels, and current and historical pain medicine literature to address core clinical considerations. To survey the current evidence base for pain management with cannabinergic medicines, a targeted PubMed search was performed to survey the percentage of positive and negative published randomized-controlled trial (RCT) results with this class of pain medicines, using appropriate search limit parameters and the keyword search string "cannabinoid OR cannabis-based AND pain." Of the 56 hits generated, 38 published RCTs met the survey criteria. Of these, 71% (27) concluded that cannabinoids had empirically demonstrable and statistically significant pain-relieving effects, whereas 29% (11) did not. Cannabis and other cannabinergic medicines' efficacies for relieving pain have been studied in RCTs, most of which have demonstrated a beneficial effect for this indication, although most trials are short-term. Adverse effects are generally nonserious and well tolerated. Incorporating cannabinergic medicine topics into pain medicine education seems warranted and continuing clinical research and empiric treatment trials are appropriate.

Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

PubMed Central

Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma

2018-01-01

Background Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. Methods We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. Results We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. PMID:28780577

A preliminary investigation on the efficacy of N-acetyl cysteine for mania or hypomania.

PubMed

Magalhães, Pedro Vieira da Silva; Dean, Olivia M; Bush, Ashley I; Copolov, David L; Malhi, Gin S; Kohlmann, Kristy; Jeavons, Susan; Schapkaitz, Ian; Anderson-Hunt, Murray; Berk, Michael

2013-06-01

Oxidative imbalance has emerged as a treatment target in bipolar disorder. As very limited data are available on the clinical use of antioxidants for mania, we report here results from a post hoc and exploratory subgroup analysis of a randomized, placebo-controlled trial of N-acetyl cysteine (NAC). This was a placebo-controlled, randomized, clinical trial assessing the effect of NAC over 24 weeks in mania or hypomania. Symptomatic and functional outcomes were collected over the study period. Fifteen participants were available for this report; two participants in each group failed to complete all assessments. Within-group analyses pointed to an improvement in the NAC group on manic symptoms and worsening in the placebo group on depressive symptoms at endpoint. Although the sample size was small, these results indicated within-group efficacy for this glutathione precursor as compared to placebo. Future trials specifically designed to demonstrate the efficacy of NAC in mania are needed.

Combined Cognitive-Strategy and Task-Specific Training Affects Cognition and Upper-Extremity Function in Subacute Stroke: An Exploratory Randomized Controlled Trial

PubMed Central

Polatajko, Helene; Baum, Carolyn; Rios, Jorge; Cirone, Dianne; Doherty, Meghan; McEwen, Sara

2016-01-01

The purpose of this study was to estimate the effect of Cognitive Orientation to Daily Occupational Performance (CO–OP) compared with usual occupational therapy on upper-extremity movement, cognitive flexibility, and stroke impact in people less than 3 mo after stroke. An exploratory, single-blind randomized controlled trial was conducted with people referred to outpatient occupational therapy services at two rehabilitation centers. Arm movement was measured with the Action Research Arm Test, cognitive flexibility with the Delis–Kaplan Executive Function System Trail Making subtest, and stroke impact with subscales of the Stroke Impact Scale. A total of 35 participants were randomized, and 26 completed the intervention. CO–OP demonstrated measurable effects over usual care on all measures. These data provide early support for the use of CO–OP to improve performance and remediate cognitive and arm movement impairments after stroke over usual care; however, future study is warranted to confirm the effects observed in this trial. PMID:26943113

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

PubMed

Liu, Joseph L Y; Wyatt, Jeremy C

2011-01-01

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

Role of rasagiline in treating Parkinson's disease: Effect on disease progression.

PubMed

Malaty, Irene A; Fernandez, Hubert H

2009-08-01

Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B) inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson's disease (PD) patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients), and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off", and Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily). Preclinical data abound to suggest potential for neuroprotection by this compound against a variety of neurotoxic insults in cell cultures and in animals. The lack of amphetamine metabolites provides an advantage over the first generation MAO-B inhibitor selegiline. One large trial has investigated the potential for disease modification in PD patients (Attenuation of Disease progression with Azilect Given Once-daily) and preliminary results maintain some possible advantage to earlier initiation of the 1 mg/day dose. The clinical significance of the difference detected remains a consideration.

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

PubMed Central

Wyatt, Jeremy C

2011-01-01

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

Replicability of sight word training and phonics training in poor readers: a randomised controlled trial

PubMed Central

Kohnen, S; Jones, K; Eve, P; Banales, E; Larsen, L; Castles, A

2015-01-01

Given the importance of effective treatments for children with reading impairment, paired with growing concern about the lack of scientific replication in psychological science, the aim of this study was to replicate a quasi-randomised trial of sight word and phonics training using a randomised controlled trial (RCT) design. One group of poor readers (N = 41) did 8 weeks of phonics training (i.e., phonological decoding) and then 8 weeks of sight word training (i.e., whole-word recognition). A second group did the reverse order of training. Sight word and phonics training each had a large and significant valid treatment effect on trained irregular words and word reading fluency. In addition, combined sight word and phonics training had a moderate and significant valid treatment effect on nonword reading accuracy and fluency. These findings demonstrate the reliability of both phonics and sight word training in treating poor readers in an era where the importance of scientific reliability is under close scrutiny. PMID:26019992

Physical activity programs for promoting bone mineralization and growth in preterm infants.

PubMed

Schulzke, Sven M; Kaempfen, Siree; Trachsel, Daniel; Patole, Sanjay K

2014-04-22

Lack of physical stimulation may contribute to metabolic bone disease of preterm infants, resulting in poor bone mineralization and growth. Physical activity programs combined with adequate nutrition might help to promote bone mineralization and growth. The primary objective was to assess whether physical activity programs in preterm infants improve bone mineralization and growth and reduce the risk of fracture.The secondary objectives included other potential benefits in terms of length of hospital stay, skeletal deformities and neurodevelopmental outcomes, and adverse events.Subgroup analysis:• Given that the smallest infants are most vulnerable for developing osteopenia (Bishop 1999), a subgroup analysis was planned for infants with birth weight < 1000 g.• Calcium and phosphorus intake may affect an infant's ability to increase bone mineral content (Kuschel 2004). Therefore, an additional subgroup analysis was planned for infants receiving different amounts of calcium and phosphorus, along with full enteral feeds as follows. ∘ Below 100 mg/60 mg calcium/phosphorus or equal to/above 100 mg/60 mg calcium/phosphorus per 100 mL milk. ∘ Supplementation of calcium without phosphorus. ∘ Supplementation of phosphorus without calcium. The standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used. The search included the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 9), MEDLINE, EMBASE, CINAHL (1966 to March 2013), and cross-references, as well as handsearching of abstracts of the Society for Pediatric Research and the International Journal of Sports Medicine. Randomized and quasi-randomized controlled trials comparing physical activity programs (extension and flexion, range-of-motion exercises) versus no organized physical activity programs in preterm infants. Data collection, study selection, and data analysis were performed according to the methods of the CNRG. Eleven trials enrolling 324 preterm infants (gestational age 26 to 34 weeks) were included in this review. All were small (N = 16 to 50) single-center studies that evaluated daily physical activity for three and one-half to eight weeks during initial hospitalization. Methodological quality and reporting of included trials were variable.Four trials demonstrated moderate short-term benefits of physical activity for bone mineralization at completion of the physical activity program. The only trial assessing long-term effects on bone mineralization showed no effect of physical activity administered during initial hospitalization on bone mineralization at 12 months corrected age. Meta-analysis from four trials demonstrated a positive effect of physical activity on daily weight gain (weighted mean difference (WMD) 2.21 g/kg/d, 95% confidence interval (CI) 1.23 to 3.19). Data from four trials showed a positive effect on linear growth (WMD 0.12 cm/wk, 95% CI 0.01 to 0.24) but not on head growth (WMD -0.03 cm/wk, 95% CI -0.14 to 0.08) during the study period. Only one trial reported on fractures (this outcome did not occur in intervention and control groups) and complications of preterm birth (no significant differences between intervention and control groups). None of the trials assessed other outcomes relevant to this review. Some evidence suggests that physical activity programs might promote short-term weight gain and bone mineralization in preterm infants. Data are inadequate to allow assessment of harm or long-term effects. Current evidence does not support the routine use of physical activity programs in preterm infants. Further trials incorporating infants with a high baseline risk of osteopenia are required. These trials should address adverse events, long-term outcomes, and the effects of nutritional intake (calories, protein, calcium, phosphorus).

Provider training and experience for people living with HIV/AIDS.

PubMed

Rackal, Julia M; Tynan, Anne-Marie; Handford, Curtis D; Rzeznikiewiz, Damian; Agha, Ayda; Glazier, Richard

2011-06-15

The complexity of HIV/AIDS raises challenges for the effective delivery of care. It is important to ensure that the expertise and experience of care providers is of high quality. Training and experience of HIV/AIDS providers may impact not only individual patient outcomes but increasingly on health care costs as well. The objective of this review is to assess the effects of provider training and experience on people living with HIV/AIDS on the following outcomes: immunological (ie. viral load, CD4 count), medical (ie. mortality, proportion on antiretrovirals), psychosocial (ie. quality of life measures) and economic outcomes (ie health care costs). We searched MEDLINE, EMBASE, Dissertation Abstracts International (DAI), CINAHL, HealthStar, PsycInfo, PsycLit, Social Sciences Abstracts, and Sociological Abstracts from January 1, 1980 through May 29, 2009.  Electronic searches were performed for abstracts from major international AIDS conferences. Reference lists from pertinent articles, books and review articles were retrieved and reviewed. Randomized controlled trials (RCTs), controlled clinical trials, cohort, case control, cross-sectional studies and controlled before and after designs that examined the qualifications/training and patient volume of HIV/AIDS care of providers caring for persons known to be infected with HIV/AIDS were included. At least two authors independently assessed trial quality and extracted data. Study authors were contacted for further information as required. Assessment of confounding factors was undertaken independently by two reviewers. A total of four studies (one randomized controlled trial, three non- randomized studies) involving 8488 people living with HIV/AIDS were included. The main findings of this review demonstrated a trend to improved outcomes when treated by a provider with more training/expertise in HIV/AIDS care in the outpatient (clinic) setting. Due to the heterogeneity of the included studies, we could not perform a meta-analysis. We present a descriptive review of the results. The results demonstrate improved medical outcomes when treated by a provider with more training/expertise in HIV/AIDS care in the outpatient (clinic) setting. Since all of these studies were conducted in North America, this does not address any issues regarding the level of training/expertise required by providers working in countries with more limited resources. Practitioners who do not consider themselves 'experts' in HIV/AIDS care and care for few of these patients need to seriously consider this review which demonstrates a trend towards worse patient outcomes when receiving care by those with low caseloads/training in HIV/AIDS care.

Trial endpoints for drug approval in oncology: Chemoprevention.

PubMed

Beitz, J

2001-04-01

As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

Renal Denervation: a Field in Flux.

PubMed

Laffin, Luke J; Bakris, George L

2016-07-01

SYMPLICITY HTN-3 was a pivotal moment for renal denervation as a treatment option for resistant hypertension. Prior unblinded studies were called into question given the negative results of the first sham-controlled trial of renal denervation. Reevaluation of the renal denervation procedure demonstrated that a more precise approach was needed to adequately denervate the kidney. This new approach has been implemented in two ongoing clinical trials, one on and one off medications to assess the new procedure's efficacy and safety. These and other ongoing trials will be discussed in the context of older studies in this field. We focus on novel findings published following the release of SYMPLICITY HTN-3 data in early 2014 and look to the future of renal denervation in the treatment of primary hypertension.

A clinical trial gone awry: the Chocolate Happiness Undergoing More Pleasantness (CHUMP) study.

PubMed

Chan, Kevin

2007-12-04

The randomized controlled trial is the "gold standard" for evaluating the benefits and harms of interventions. The Chocolate Happiness Undergoing More Pleasantness (CHUMP) study was designed to compare the effects of dark chocolate, milk chocolate and normal chocolate consumption on happiness. Although the intention-to-treat analysis showed that participants who received either dark or milk chocolate were happier than those who received no additional chocolate, the actual-consumption analysis showed that there were no differences between any of the groups. The reason for this result is that many participants switched groups mid-study because of their personal chocolate preferences. Although the CHUMP study was pleasurable, it demonstrated the difficulties associated with performing a truly blinded clinical trial.

A clinical trial gone awry: the Chocolate Happiness Undergoing More Pleasantness (CHUMP) study

PubMed Central

Chan, Kevin

2007-01-01

The randomized controlled trial is the “gold standard” for evaluating the benefits and harms of interventions. The Chocolate Happiness Undergoing More Pleasantness (CHUMP) study was designed to compare the effects of dark chocolate, milk chocolate and normal chocolate consumption on happiness. Although the intention-to-treat analysis showed that participants who received either dark or milk chocolate were happier than those who received no additional chocolate, the actual-consumption analysis showed that there were no differences between any of the groups. The reason for this result is that many participants switched groups mid-study because of their personal chocolate preferences. Although the CHUMP study was pleasurable, it demonstrated the difficulties associated with performing a truly blinded clinical trial. PMID:18056618

Results from the Trial Using Motivational Interviewing, Positive Affect, and Self-Affirmation in African Americans with Hypertension (TRIUMPH).

PubMed

Boutin-Foster, Carla; Offidani, Emanuela; Kanna, Balavenkatesh; Ogedegbe, Gbenga; Ravenell, Joseph; Scott, Ebony; Rodriguez, Anna; Ramos, Rosio; Michelen, Walid; Gerber, Linda M; Charlson, Mary

2016-01-21

Our objective was to determine the effectiveness of combining positive affect and self-affirmation strategies with motivational interviewing in achieving blood pressure control among hypertensive African Americans (AA) compared with AA hypertensives in an education-only control group. Randomized trial. Ambulatory practices in the South Bronx and Harlem, New York City. African American adults with uncontrolled hypertension. Participants were randomized to a positive affect and self-affirmation intervention or an education control group. The positive affect and self-affirmation intervention involved having participants think about things that made them happy and that reminded them of their core values on a daily basis. These strategies were reinforced every two months through motivational interviewing. The control arm received a workbook of strategies on blood pressure control. All participants were called every two months for one year. Blood pressure control rate. A total of 238 participants were randomized. The average age was 56 ± 11 years, approximately 70% were female, 80% were not married, and up to 70% had completed high school. There was no difference in control rates between the intervention and the control group. However, at one year, female participants were more likely to be controlled. Participants with high depressive symptoms or high perceived stress at baseline were less likely to be controlled. While this study did not demonstrate an intervention effect, it does provide important insight into the psychosocial factors that may underlie blood pressure control in African Americans. Implications for future behavioral intervention trials are discussed.

A Design to Investigate the Feasibility and Effects of Partnered Ballroom Dancing on People With Parkinson Disease: Randomized Controlled Trial Protocol

PubMed Central

Roberts, Lisa; Pickering, Ruth; Roberts, Helen Clare; Wiles, Rose; Kunkel, Dorit; Hulbert, Sophia; Robison, Judy; Fitton, Carolyn

2014-01-01

Background Self-help and physical leisure activities has become increasingly important in the maintenance of safe and functional mobility among an increasingly elderly population. Preventing the cycle of deterioration, falling, inactivity, dependency, and secondary complications in people with Parkinson disease (PD) is a priority. Research has shown that people with PD are interested in dance and although the few existing trials are small, initial proof of principle trials from the United States have demonstrated beneficial effects on balance control, gait, and activity levels. To our knowledge, there has been no research into long-term effects, cost effectiveness, the influence on spinal posture and turning, or the personal insights of dance participants. Objective The purpose of this study was to determine the methodological feasibility of conducting a definitive phase III trial to evaluate the benefits of dance in people with PD. We will build on the proof of principle trials by addressing gaps in knowledge, focusing on areas of greatest methodological uncertainty; the choice of dances and intensity of the program; for the main trial, the availability of partners, the suitability of the currently envisaged primary outcomes, balance and spinal posture; and the key costs of delivering and participating in a dance program to inform economic evaluation. Methods Fifty participants (mild-to-moderate condition) will be randomized to the control (usual care) or experimental (dance plus usual care) groups at a ratio of 15:35. Dance will be taught by professional teachers in a dance center in the South of England. Each participant in the experimental group will dance with his or her spouse, a friend, or a partner from a bank of volunteers. A blinded assessor will complete clinical measures and self-reported ability at baseline, and at 3 and 6 months after randomization. A qualitative study of a subgroup of participants and partners will examine user’s views about the appropriateness and acceptability of the intervention, assessment protocol, and general trial procedures. Procedures for an economic evaluation of dance for health care will be developed for the main trial. Results Recruitment began in January 2013 and the last participant is expected to complete the trial follow-up in June 2014. Conclusions Findings from our study may provide novel insights into the way people with PD become involved in dance, their views and opinions, and the suitability of our primary and secondary outcomes. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 63088686; http://www.controlled-trials.com/ISRCTN63088686/63088686 (Archived by WebCite at http://www.webcitation.org/6QYyjehP7). PMID:25051989

Perceiving emotions: Cueing social categorization processes and attentional control through facial expressions.

PubMed

Cañadas, Elena; Lupiáñez, Juan; Kawakami, Kerry; Niedenthal, Paula M; Rodríguez-Bailón, Rosa

2016-09-01

Individuals spontaneously categorise other people on the basis of their gender, ethnicity and age. But what about the emotions they express? In two studies we tested the hypothesis that facial expressions are similar to other social categories in that they can function as contextual cues to control attention. In Experiment 1 we associated expressions of anger and happiness with specific proportions of congruent/incongruent flanker trials. We also created consistent and inconsistent category members within each of these two general contexts. The results demonstrated that participants exhibited a larger congruency effect when presented with faces in the emotional group associated with a high proportion of congruent trials. Notably, this effect transferred to inconsistent members of the group. In Experiment 2 we replicated the effects with faces depicting true and false smiles. Together these findings provide consistent evidence that individuals spontaneously utilise emotions to categorise others and that such categories determine the allocation of attentional control.

A Yoga Intervention for Posttraumatic Stress: A Preliminary Randomized Control Trial.

PubMed

Jindani, Farah; Turner, Nigel; Khalsa, Sat Bir S

2015-01-01

Yoga may be effective in the reduction of PTSD symptomology. The purpose of this study was to evaluate the impact of a Kundalini Yoga (KY) treatment on PTSD symptoms and overall wellbeing. To supplement the current field of inquiry, a pilot randomized control trial (RCT) was conducted comparing an 8-session KY intervention with a waitlist control group. 80 individuals with current PTSD symptoms participated. Both groups demonstrated changes in PTSD symptomology but yoga participants showed greater changes in measures of sleep, positive affect, perceived stress, anxiety, stress, and resilience. Between-groups effect sizes were small to moderate (0.09-0.25). KY may be an adjunctive or alternative intervention for PTSD. Findings indicate the need for further yoga research to better understand the mechanism of yoga in relation to mental and physical health, gender and ethnic comparisons, and short- and long-term yoga practice for psychiatric conditions.

A Yoga Intervention for Posttraumatic Stress: A Preliminary Randomized Control Trial

PubMed Central

Jindani, Farah; Turner, Nigel; Khalsa, Sat Bir S.

2015-01-01

Yoga may be effective in the reduction of PTSD symptomology. The purpose of this study was to evaluate the impact of a Kundalini Yoga (KY) treatment on PTSD symptoms and overall wellbeing. To supplement the current field of inquiry, a pilot randomized control trial (RCT) was conducted comparing an 8-session KY intervention with a waitlist control group. 80 individuals with current PTSD symptoms participated. Both groups demonstrated changes in PTSD symptomology but yoga participants showed greater changes in measures of sleep, positive affect, perceived stress, anxiety, stress, and resilience. Between-groups effect sizes were small to moderate (0.09–0.25). KY may be an adjunctive or alternative intervention for PTSD. Findings indicate the need for further yoga research to better understand the mechanism of yoga in relation to mental and physical health, gender and ethnic comparisons, and short- and long-term yoga practice for psychiatric conditions. PMID:26366179

Short-term outcomes of local infiltration anaesthetic in total knee arthroplasty: a randomized controlled double-blinded controlled trial.

PubMed

Mulford, Jonathan S; Watson, Anna; Broe, David; Solomon, Michael; Loefler, Andreas; Harris, Ian

2016-03-01

The primary objective of the study was to determine if local infiltration anaesthetic (LIA) reduced total length of hospital stay in total knee arthroplasty (TKA) patients. The study also examined whether LIA improves early pain management, patient satisfaction and range of motion in TKA patients. We conducted a randomized controlled double-blinded study. Fifty patients undergoing TKA were randomized to receive either placebo or LIA at the time of surgery and on the first day post-operatively. Pain scores, level of satisfaction and range of motion were recorded preoperatively and post-operatively. There was no statistical difference between the groups for length of stay, post-operative pain scores, satisfaction scores or range of motion 6 weeks post-operatively. This randomized double-blinded trial did not demonstrate a decrease in pain or reduction of length of stay due to local infiltration analgesia. © 2015 Royal Australasian College of Surgeons.

Study design and rationale of the 'Balloon-Expandable Cobalt Chromium SCUBA Stent versus Self-Expandable COMPLETE-SE Nitinol Stent for the Atherosclerotic ILIAC Arterial Disease (SENS-ILIAC Trial) Trial': study protocol for a randomized controlled trial.

PubMed

Choi, Woong Gil; Rha, Seung Woon; Choi, Cheol Ung; Kim, Eung Ju; Oh, Dong Joo; Cho, Yoon Hyung; Park, Sang Ho; Lee, Seung Jin; Hur, Ae Yong; Ko, Young Guk; Park, Sang Min; Kim, Ki Chang; Kim, Joo Han; Kim, Min Woong; Kim, Sang Min; Bae, Jang Ho; Bong, Jung Min; Kang, Won Yu; Seo, Jae Bin; Jung, Woo Yong; Cho, Jang Hyun; Kim, Do Hoi; Ahn, Ji Hoon; Kim, Soo Hyun; Jang, Ji Yong

2016-06-25

The self-expandable COMPLETE™ stent (Medtronic) has greater elasticity, allowing it to regain its shape after the compression force reduces, and has higher trackability, thus is easier to maneuver through tortuous vessels, whereas the balloon-expandable SCUBA™ stent (Medtronic) has higher radial stiffness and can afford more accurate placement without geographic miss, which is important in aortoiliac bifurcation lesions. To date, there have been no randomized control trials comparing efficacy and safety between the self-expanding stent and balloon-expandable stent in advanced atherosclerotic iliac artery disease. The purpose of our study is to examine primary patency (efficacy) and incidence of stent fracture and geographic miss (safety) between two different major representative stents, the self-expanding nitinol stent (COMPLETE-SE™) and the balloon-expanding cobalt-chromium stent (SCUBA™), in stenotic or occlusive iliac arterial lesions. This trial is designed as a prospective, randomized, multicenter trial to demonstrate a noninferiority of SCUBA™ stent to COMPLETE-SE™ stent following balloon angioplasty in iliac arterial lesions, and a total of 280 patients will be enrolled. The primary end point of this study is the rate of primary patency in the treated segment at 12 months after intervention as determined by catheter angiography, computed tomography angiography, or duplex ultrasound. The SENS-ILIAC trial will give powerful insight into whether the stent choice according to deployment mechanics would impact stent patency, geographic miss, or stent fracture in patients undergoing stent implantation in iliac artery lesions. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT01834495 ), registration date: May 8, 2012.

TOPPITS: Trial Of Proton Pump Inhibitors in Throat Symptoms. Study protocol for a randomised controlled trial.

PubMed

Watson, Gillian; O'Hara, James; Carding, Paul; Lecouturier, Jan; Stocken, Deborah; Fouweather, Tony; Wilson, Janet

2016-04-01

Persistent throat symptoms and Extra Oesophageal Reflux (EOR) are among the commonest reasons for attendance at a secondary care throat or voice clinic. There is a growing trend to treat throat symptom patients with proton pump inhibitors (PPIs) to suppress stomach acid, but most controlled studies fail to demonstrate a significant benefit of PPI over placebo. In addition, patient views on PPI use vary widely. A UK multi-centre, randomised, controlled trial for adults with persistent throat symptoms to compare the effectiveness of treatment with the proton pump inhibitor (PPI) lansoprazole versus placebo. The trial includes a six-month internal pilot, during which three sites will recruit 30 participants in total, to assess the practicality of the trial and assess the study procedures and willingness of the patient population to participate. If the pilot is successful, three additional sites will be opened to recruitment, and a further 302 participants recruited across the six main trial sites. Further trial sites may be opened, as necessary. The main trial will continue for a further 18 months. Participants will be followed up for 12 months from randomisation, throughout which both primary and secondary outcome data will be collected. The primary outcome is change in Reflux Symptom Index (RSI) score, the 'area standard' for this type of assessment, after 16 weeks (four months) of treatment. Secondary outcomes are RSI changes at 12 months after randomisation, Quality of Life assessment at four and 12 months, laryngeal mucosal changes, assessments of compliance and side effects, and patient-reported satisfaction. TOPPITS is designed to evaluate the relative effectiveness of treatment with a proton pump inhibitor versus placebo in patients with persistent throat symptoms. This will provide valuable information to clinicians and GPs regarding the treatment and management of care for these patients, on changes in symptoms, and in Quality of Life, over time. ISRCTN38578686 . Registered 17 April 2014.

The transvaginal hybrid NOTES versus conventionally assisted laparoscopic sigmoid resection for diverticular disease (TRANSVERSAL) trial: study protocol for a randomized controlled trial.

PubMed

Senft, Jonas D; Warschkow, Rene; Diener, Markus K; Tarantino, Ignazio; Steinemann, Daniel C; Lamm, Sebastian; Simon, Thomas; Zerz, Andreas; Müller-Stich, Beat P; Linke, Georg R

2014-11-20

Natural orifice transluminal endoscopic surgery (NOTES) is the consequence of further development of minimally invasive surgery to reduce abdominal incisions and surgical trauma. The potential benefits are expected to be less postoperative pain, faster convalescence, and reduced risk for incisional hernias and wound infections compared to conventional methods. Recent clinical studies have demonstrated the feasibility and safety of transvaginal NOTES, and transvaginal access is currently the most frequent clinically applied route for NOTES procedures. However, despite increasing clinical application, no firm clinical evidence is available for objective assessment of the potential benefits and risks of transvaginal NOTES compared to the current surgical standard. The TRANSVERSAL trial is designed as a randomized controlled trial to compare transvaginal hybrid NOTES and laparoscopic-assisted sigmoid resection. Female patients referred to elective sigmoid resection due to complicated or reoccurring diverticulitis of the sigmoid colon are considered eligible. The primary endpoint will be pain intensity during mobilization 24 hours postoperatively as measured by the blinded patient and blinded assessor on a visual analogue scale (VAS). Secondary outcomes include daily pain intensity and analgesic use, patient mobility, intraoperative complications, morbidity, length of stay, quality of life, and sexual function. Follow-up visits are scheduled 3, 12, and 36 months after surgery. A total sample size of 58 patients was determined for the analysis of the primary endpoint. The confirmatory analysis will be performed based on the intention-to-treat (ITT) principle. The TRANSVERSAL trial is the first study to compare transvaginal hybrid NOTES and conventionally assisted laparoscopic surgery for colonic resection in a randomized controlled setting. The results of the TRANSVERSAL trial will allow objective assessment of the potential benefits and risks of NOTES compared to the current surgical standard for sigmoid resection. The trial protocol was registered in the German Clinical Trials Register ( DRKS00005995) on March 27, 2014.

The natural history of subjective tinnitus in adults: A systematic review and meta-analysis of no-intervention periods in controlled trials.

PubMed

Phillips, John S; McFerran, Don J; Hall, Deborah A; Hoare, Derek J

2018-01-01

Tinnitus is a prevalent condition, but little has been published regarding the natural history of the condition. One technique for evaluating the long-term progression of the disease is to examine what happens to participants in the no-intervention control arm of a clinical trial. The aim of this study was to examine no-intervention or waiting-list data reported in trials, in which participants on the active arm received any form of tinnitus intervention. CINAHL, PsychINFO, EMBASE, ASSIA, PubMed, Web of Science, Science Direct, EBSCO Host, and Cochrane. Inclusion criteria followed the PICOS principles: Participants, adults with tinnitus; Intervention, none; Control, any intervention for alleviating tinnitus; Outcomes, a measure assessing tinnitus symptoms using a multi-item patient-reported tinnitus questionnaire. Secondary outcome measures included multi-item patient-reported questionnaires of mood and health-related quality of life and measures that quantified change in tinnitus loudness; Study design, randomized controlled trials or observational studies utilizing a no-intervention or waiting-list control group. Data were extracted and standardized mean difference was calculated for each study to enable meta-analysis. The evidence strongly favored a statistically significant decrease in the impact of tinnitus over time, though there was significant heterogeneity and clinical significance cannot be interpreted. Outcome data regarding secondary measures did not demonstrate any clinically significant change. Participants allocated to the no-intervention or waiting-list control arm of clinical trials for a tinnitus intervention show a small but significant improvement in self-reported measures of tinnitus with time; the clinical significance of this finding is unknown. There is, however, considerable variation across individuals. These findings support previous work and can cautiously be used when counseling patients. Laryngoscope, 128:217-227, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Rituximab in systemic lupus erythematosus and lupus nephritis.

PubMed

Beckwith, Hannah; Lightstone, Liz

2014-01-01

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

Efficacy and safety of Vernonia cinerea (L.) Less. for smoking cessation: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Puttarak, Panupong; Pornpanyanukul, Patarachai; Meetam, Thunyaluk; Bunditanukul, Katha; Chaiyakunapruk, Nathorn

2018-04-01

Several randomized controlled trials have investigated Vernonia cinerea (L.) Less. for smoking cessation but there remains no critical summary of overall findings. This study uses systematic review and meta-analysis to summarize the efficacy and safety of V. cinerea. Nine databases were searched through November 2017. Randomized controlled trials that reported the smoking cessation effect of V. cinerea were included. Data were extracted by two independent researchers. Study quality was assessed using the Cochrane risk of bias and JADAD score. The estimates of pooled effects were calculated as relative risk (RR) with 95% CI using a random-effects model. Five trials with 347 smokers were included. V. cinerea treatment group was significantly associated with cessation rate higher than that in the control group with no evidence of heterogeneity for both continuous abstinence rate (CAR) at week 8 with risk ratio (RR): 1.69, 95% CI [1.00, 2.86]; week 12 RR: 2.18, 95% CI [1.17, 4.04]) and 7-day point prevalence abstinence rate (PAR) (week 8 RR: 1.51, 95% CI [1.01, 2.27]; week 12 RR: 1.93, 95% CI [1.24, 2.99]) at week 8 and 12, respectively. There was no significant difference of all adverse events between the treatment and the control groups. Our study demonstrates that V. cinerea has potential efficacy for smoking cessation. Further well-design RCTs of standardized V. cinerea compared with standard treatment should be conducted to strengthen this evidence. Copyright © 2018 Elsevier Ltd. All rights reserved.

Efficacy of probiotic use in acute rotavirus diarrhea in children: A systematic review and meta-analysis

PubMed Central

Ahmadi, Elaheh; Alizadeh-Navaei, Reza; Rezai, Mohammad Sadegh

2015-01-01

Background: Probiotic therapies with different strains demonstrated some beneficial effects, although some studies did not show any significant effects. This study assessed systematically the current knowledge on the effect of probiotic bacteria on duration of acute rotavirus diarrhea in children compared with control. Methods: The PubMed, Cochrane Controlled Trial Register (CCTR) and Ovid (Wolters Kluwer Health) were searched between 1980 to June 15, 2013. Randomized controlled trials including the administration of probiotics for treatment of rotavirus diarrhea in infants and children were reviewed. Results: A total number of 1244 articles were found through the aforementioned search. 203 articles were selected after the first screening of title and abstract. The intervention group included subjects who received probiotic strains and dosage in any conditions. Placebo or any similar vehicle without probiotic was used in the controlled trials. Finally, 14 articles were selected. The outcomes from each study were considered in the duration of diarrhea. Statistical analyses were performed with Stata software. The pooled estimate of efficacy of probiotics in prevention or treatment of disease yielded in all studies a mean difference of 0.41 (CI 95%: -0.56 to –0.25; p<0.001). The pooled estimate of efficacy of lactobacillus rhamnosus GG and other probiotics significantly reduced the duration of diarrhea. Among trials, the overall reduction of LGG was 0.47 (CI 95%: -0.80 to -0.14; P= 0.020). Conclusion: In conclusion, probiotics exert positive effect in reducing the duration of acute rotavirus diarrhea compared with control. PMID:26644891

Reactive but not predictive locomotor adaptability is impaired in young Parkinson's disease patients.

PubMed

Moreno Catalá, María; Woitalla, Dirk; Arampatzis, Adamantios

2016-07-01

Gait and balance disorders are common in Parkinson's disease (PD) and major contributors to increased falling risk. Predictive and reactive adjustments can improve recovery performance after gait perturbations. However, these mechanisms have not been investigated in young-onset PD. We aimed to investigate the effect of gait perturbations on dynamic stability control as well as predictive and reactive adaptability to repeated gait perturbations in young PD patients. Fifteen healthy controls and twenty-five young patients (48±5yrs.) walked on a walkway. By means of a covered exchangeable element, the floor surface condition was altered to induce gait perturbations. The experimental protocol included a baseline on a hard surface, an unexpected trial on a soft surface and an adaptation phase with 5 soft trials to quantify the reactive adaptation. After the first and sixth soft trials, the surface was changed to hard, to examine after-effects and, thus, predictive motor control. Dynamic stability was assessed using the 'extrapolated center of mass' concept. Patients' unperturbed walking was less stable than controls' and this persisted in the perturbed trials. Both groups demonstrated after-effects directly after the first perturbation, showing similar predictive responses. However, PD patients did not improve their reactive behavior after repeated perturbations while controls showed clear locomotor adaptation. Our data suggest that more unstable gait patterns and a less effective reactive adaptation to perturbed walking may be a disease-related characteristic in young PD patients. These deficits were related to reduced ability to increase the base of support. Copyright © 2016 Elsevier B.V. All rights reserved.

Real-time myoelectric control of a multi-fingered hand prosthesis using principal components analysis.

PubMed

Matrone, Giulia C; Cipriani, Christian; Carrozza, Maria Chiara; Magenes, Giovanni

2012-06-15

In spite of the advances made in the design of dexterous anthropomorphic hand prostheses, these sophisticated devices still lack adequate control interfaces which could allow amputees to operate them in an intuitive and close-to-natural way. In this study, an anthropomorphic five-fingered robotic hand, actuated by six motors, was used as a prosthetic hand emulator to assess the feasibility of a control approach based on Principal Components Analysis (PCA), specifically conceived to address this problem. Since it was demonstrated elsewhere that the first two principal components (PCs) can describe the whole hand configuration space sufficiently well, the controller here employed reverted the PCA algorithm and allowed to drive a multi-DoF hand by combining a two-differential channels EMG input with these two PCs. Hence, the novelty of this approach stood in the PCA application for solving the challenging problem of best mapping the EMG inputs into the degrees of freedom (DoFs) of the prosthesis. A clinically viable two DoFs myoelectric controller, exploiting two differential channels, was developed and twelve able-bodied participants, divided in two groups, volunteered to control the hand in simple grasp trials, using forearm myoelectric signals. Task completion rates and times were measured. The first objective (assessed through one group of subjects) was to understand the effectiveness of the approach; i.e., whether it is possible to drive the hand in real-time, with reasonable performance, in different grasps, also taking advantage of the direct visual feedback of the moving hand. The second objective (assessed through a different group) was to investigate the intuitiveness, and therefore to assess statistical differences in the performance throughout three consecutive days. Subjects performed several grasp, transport and release trials with differently shaped objects, by operating the hand with the myoelectric PCA-based controller. Experimental trials showed that the simultaneous use of the two differential channels paradigm was successful. This work demonstrates that the proposed two-DoFs myoelectric controller based on PCA allows to drive in real-time a prosthetic hand emulator into different prehensile patterns with excellent performance. These results open up promising possibilities for the development of intuitive, effective myoelectric hand controllers.

Cognitive-behaviour therapy for post-traumatic stress in schizophrenia. A randomized controlled trial.

PubMed

Steel, C; Hardy, A; Smith, B; Wykes, T; Rose, S; Enright, S; Hardcastle, M; Landau, S; Baksh, M F; Gottlieb, J D; Rose, D; Mueser, K T

2017-01-01

There is limited evidence for effective interventions in the treatment of post-traumatic stress symptoms within individuals diagnosed with schizophrenia. Clinicians have concerns about using exposure treatments with this patient group. The current trial was designed to evaluate a 16-session cognitive restructuring programme, without direct exposure, for the treatment of post-traumatic stress symptoms specifically within individuals diagnosed with schizophrenia. A multicentre randomized controlled single-blinded trial with assessments at 0 months, 6 months (post-treatment) and 12 months (follow-up) was conducted. A total of 61 participants diagnosed with schizophrenia and exhibiting post-traumatic stress symptoms were recruited. Those randomized to treatment were offered up to 16 sessions of cognitive-behaviour therapy (CBT, including psychoeducation, breathing training and cognitive restructuring) over a 6-month period, with the control group offered routine clinical services. The main outcome was blind rating of post-traumatic stress symptoms using the Clinician Administered PTSD Scale for Schizophrenia. Secondary outcomes were psychotic symptoms as measured by the Positive and Negative Symptom Scale and the Psychotic Symptom Rating Scale. Both the treatment and control groups experienced a significant decrease in post-traumatic stress symptoms over time but there was no effect of the addition of CBT on either the primary or secondary outcomes. The current trial did not demonstrate any effect in favour of CBT. Cognitive restructuring programmes may require further adaptation to promote emotional processing of traumatic memories within people diagnosed with a psychotic disorder.

Psychosocial interventions for internalised stigma in people with a schizophrenia-spectrum diagnosis: A systematic narrative synthesis and meta-analysis.

PubMed

Wood, Lisa; Byrne, Rory; Varese, Filippo; Morrison, Anthony P

2016-10-01

It is acknowledged that people with a schizophrenia-spectrum diagnosis experience higher levels of stigma compared to any other mental health diagnosis. As a consequence, their experience of internalised stigma is likely to be the most detrimental and pervasive. Internalised stigma interventions have shown some benefits in those who experience serious mental illness including those with a schizophrenia-spectrum diagnosis. A systematic narrative review and meta-analysis were conducted examining the efficacy of internalised stigma interventions for people with a schizophrenia-spectrum diagnosis. Randomised Controlled Trials, controlled trials, and cohort studies were included and assessed against quality criteria. The search identified 12 studies; 7 randomised controlled trials, 3 cohort studies and 2 controlled trials. A variety of psychosocial interventions were utilised with the majority employing Cognitive Behaviour Therapy (CBT), psychoeducation and social skills training. The core outcomes used to examine the efficacy of the intervention were internalised stigma, self-esteem, empowerment, and functioning. The meta-analysis revealed an improvement in internalised stigma favouring the internalised stigma intervention but was not significant (5 RCTs, n=200). Self-efficacy and insight were significantly improved favouring the internalised stigma intervention. Internalised stigma interventions show promise in those with schizophrenia-spectrum diagnoses. Existing interventions have demonstrated small effects and employed small samples. Large scale RCTs are required to further develop the evidence base of more targeted interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

Ventriculoperitoneal shunt insertion for hydrocephalus in human immunodeficiency virus-infected adults: a systematic review and meta-analysis protocol.

PubMed

Loan, James J M; Mankahla, Ncedile; Meintjes, Graeme; Fieggen, A Graham

2017-10-16

Hydrocephalus is a recognised complication of human immunodeficiency virus (HIV)-related opportunistic infections. Symptomatic raised cerebrospinal fluid pressure can be treated with ventriculoperitoneal shunt insertion (VPS). In HIV-infected patients however, there is a concern that VPS might be associated with unacceptably high rates of mortality. We aim to systematically review and appraise published literature to determine reported outcomes and identify predictors of outcome following VPS in relevant subgroups of HIV-infected adults. The following electronic databases will be searched: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, CINAHL (EBSCOhost), LILACS (BIREME), Research Registry ( www.researchregistry.com ), the metaRegister of Controlled Trials (mRCT) ( www.controlled-trials.com ), ClinicalTrials.gov ( www.clinicaltrials.gov ) and OpenSIGLE database. Any randomised studies, cohort studies, case-control studies, interrupted time series or sequential case series reporting survival following VPS in HIV-infected individuals will be included. If high-quality homogenous studies exist, meta-analysis will be conducted to determine 1-, 6- and 12-month mortality with comparison made between underlying aetiologies of hydrocephalus. This study will generate a comprehensive review of VPS in HIV-infected patients for publication. The primary outcome of meta-analysis is 12-month survival. If only low-quality, heterogeneous studies are available, this study will demonstrate this deficiency and will be of value in justifying and aiding the design of future studies. PROSPERO CRD42016052239.

Home- or community-based programmes for treating malaria.

PubMed

Okwundu, Charles I; Nagpal, Sukrti; Musekiwa, Alfred; Sinclair, David

2013-05-31

Malaria is an important cause of morbidity and mortality, in particular among children and pregnant women in sub-Saharan Africa. Prompt access to diagnosis and treatment with effective antimalarial drugs is a central component of the World Health Organization's (WHO) strategy for malaria control. Home- or community-based programmes for managing malaria are one strategy that has been proposed to overcome the geographical barrier to malaria treatment.  To evaluate home- and community-based management strategies for treating malaria. We searched the Cochrane Central Register of Controlled Trials published in The Cochrane Library; MEDLINE; EMBASE; Science Citation Index; PsycINFO/LIT; CINAHL; WHO clinical trial registry platform; and the metaRegister of Controlled Trials up to September 2012. Randomized controlled trials (RCTs) and non-RCTs that evaluated the effects of a home- or community-based programme for treating malaria in a malaria endemic setting. Two authors independently screened and selected studies, extracted data, and assessed the risk of bias. Where possible 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 the GRADE approach. We identified 10 trials that met the inclusion criteria. The interventions involved brief training of basic-level health workers or mothers, and most provided the antimalarial for free or at a highly subsidized cost. In eight of the studies, fevers were treated presumptively without parasitological confirmation with microscopy or a rapid diagnostic test (RDT). Two studies trained community health workers to use RDTs as a component of community management of fever.Home- or community-based strategies probably increase the number of people with fever who receive an appropriate antimalarial within 24 hours (RR 2.27, 95% CI 1.79 to 2.88 in one trial; RR 9.79, 95% CI 6.87 to 13.95 in a second trial; 3099 participants, moderate quality evidence). They may also reduce all-cause mortality, but to date this has only been demonstrated in rural Ethiopia (RR 0.58, 95% CI 0.44 to 0.77, one trial, 13,677 participants, moderate quality evidence).Hospital admissions in children were reported in one small trial from urban Uganda, with no effect detected (437 participants, very low quality evidence). No studies reported on severe malaria. For parasitaemia prevalence, the study from urban Uganda demonstrated a reduction in community parasite prevalence (RR 0.22, 95% CI 0.08 to 0.64, 365 participants), but a second study in rural Burkina Faso did not (1006 participants). Home- or community-based programmes may have little or no effect on the prevalence of anaemia (three trials, 3612 participants, low quality evidence). None of the included studies reported on adverse effects of using home- or community-based programmes for treating malaria.In two studies which trained community health workers to only prescribe antimalarials after a positive RDT, prescriptions of antimalarials were reduced compared to the control group where community health workers used clinical diagnosis (RR 0.39, 95% CI 0.18 to 0.84, two trials, 5944 participants, moderate quality evidence). In these two studies, mortality and hospitalizations remained very low in both groups despite the lower use of antimalarials (two trials, 5977 participants, low quality evidence). Home- or community-based interventions which provide antimalarial drugs free of charge probably improve prompt access to antimalarials, and there is moderate quality evidence from rural Ethiopia that they may impact on childhood mortality when implemented in appropriate settings.Programmes which treat all fevers presumptively with antimalarials lead to overuse antimalarials, and potentially undertreat other causes of fever such as pneumonia. Incorporating RDT diagnosis into home- or community-based programmes for malaria may help to reduce this overuse of antimalarials, and has been shown to be safe under trial conditions.

Economic evaluations of Internet interventions for mental health: a systematic review.

PubMed

Donker, T; Blankers, M; Hedman, E; Ljótsson, B; Petrie, K; Christensen, H

2015-12-01

Internet interventions are assumed to be cost-effective. However, it is unclear how strong this evidence is, and what the quality of this evidence is. A comprehensive literature search (1990-2014) in Medline, EMBASE, the Cochrane Central Register of Controlled Trials, NHS Economic Evaluations Database, NHS Health Technology Assessment Database, Office of Health Economics Evaluations Database, Compendex and Inspec was conducted. We included economic evaluations alongside randomized controlled trials of Internet interventions for a range of mental health symptoms compared to a control group, consisting of a psychological or pharmaceutical intervention, treatment-as-usual (TAU), wait-list or an attention control group. Of the 6587 abstracts identified, 16 papers met the inclusion criteria. Nine studies featured a societal perspective. Results demonstrated that guided Internet interventions for depression, anxiety, smoking cessation and alcohol consumption had favourable probabilities of being more cost-effective when compared to wait-list, TAU, group cognitive behaviour therapy (CBGT), attention control, telephone counselling or unguided Internet CBT. Unguided Internet interventions for suicide prevention, depression and smoking cessation demonstrated cost-effectiveness compared to TAU or attention control. In general, results from cost-utility analyses using more generic health outcomes (quality of life) were less favourable for unguided Internet interventions. Most studies adhered reasonably to economic guidelines. Results of guided Internet interventions being cost-effective are promising with most studies adhering to publication standards, but more economic evaluations are needed in order to determine cost-effectiveness of Internet interventions compared to the most cost-effective treatment currently available.

Cosmesis, patient satisfaction, and quality of life after da Vinci Single-Site cholecystectomy and multiport laparoscopic cholecystectomy: short-term results from a prospective, multicenter, randomized, controlled trial.

PubMed

Kudsi, Omar Yusef; Castellanos, Andres; Kaza, Srinivas; McCarty, Justin; Dickens, Eugene; Martin, David; Tiesenga, Frederick M; Konstantinidis, Konstantinos; Hirides, Petros; Mehendale, Shilpa; Gonzalez, Anthony

2017-08-01

Single-incision laparoscopic cholecystectomy evolved from the traditional multiport laparoscopic technique. Prior trials have demonstrated improved cosmesis with the single-incision technique. Robotic single-site surgery minimizes the technical difficulties associated with laparoscopic single-incision approach. This is the first prospective, randomized, controlled study comparing robotic single-site cholecystectomy (RSSC) and multiport laparoscopic cholecystectomy (MPLC) in terms of cosmesis and patient satisfaction. Patients with symptomatic benign gallbladder disease were randomized to RSSC or MPLC. Data included perioperative variables such as operative time, conversion and complications and cosmesis satisfaction, body image perception, quality of life using validated questionnaires, at postoperative visits of 2, 6 weeks and 3 months. One hundred thirty-six patients were randomized to RSSC (N = 83) and MPLC (N = 53) at 8 institutions. Both cohorts were dominated by higher enrollment of females (RSSC = 78%, MPLC = 92%). The RSSC and MPLC cohorts were otherwise statistically matched. Operative time was longer for RSSC (61 min vs. 44 min, P < 0.0001). There were no differences in complication rates. RSSC demonstrated a significant superiority in cosmesis satisfaction and body image perception (P value < 0.05 at every follow-up). There was no statistically significant difference in patient-reported quality of life. Multivariate analysis of female patients demonstrated significantly higher preference for RSSC over MPLC in cosmesis satisfaction and body image perception with no difference seen in overall quality of life. Results from this trial show that RSSC is associated with improved cosmesis satisfaction and body image perception without a difference in observed complication rate. The uncompromised safety and the improved cosmesis satisfaction and body image perception provided by RSSC for female patients support consideration of the robotic single-site approach. ClinicalTrials.gov identifier NCT01932216.

Statistical Approaches to Adjusting Weights for Dependent Arms in Network Meta-analysis.

PubMed

Su, Yu-Xuan; Tu, Yu-Kang

2018-05-22

Network meta-analysis compares multiple treatments in terms of their efficacy and harm by including evidence from randomized controlled trials. Most clinical trials use parallel design, where patients are randomly allocated to different treatments and receive only one treatment. However, some trials use within person designs such as split-body, split-mouth and cross-over designs, where each patient may receive more than one treatment. Data from treatment arms within these trials are no longer independent, so the correlations between dependent arms need to be accounted for within the statistical analyses. Ignoring these correlations may result in incorrect conclusions. The main objective of this study is to develop statistical approaches to adjusting weights for dependent arms within special design trials. In this study, we demonstrate the following three approaches: the data augmentation approach, the adjusting variance approach, and the reducing weight approach. These three methods could be perfectly applied in current statistic tools such as R and STATA. An example of periodontal regeneration was used to demonstrate how these approaches could be undertaken and implemented within statistical software packages, and to compare results from different approaches. The adjusting variance approach can be implemented within the network package in STATA, while reducing weight approach requires computer software programming to set up the within-study variance-covariance matrix. This article is protected by copyright. All rights reserved.

Lubiprostone: in constipation-predominant irritable bowel syndrome.

PubMed

Carter, Natalie J; Scott, Lesley J

2009-06-18

Lubiprostone is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of human gastrointestinal epithelial cells, thereby increasing chloride-rich fluid secretion. Although the mechanism is unclear, this may then decrease intestinal transit time, allowing the passage of stool and alleviating symptoms of constipation. Oral lubiprostone was effective in the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C) in large (n = 193-583) phase II (dose-finding) and phase III randomized, double-blind, placebo-controlled, multicentre trials. The number of patients with IBS-C demonstrating an overall response to treatment (primary endpoint) in the two phase III trials was significantly greater in patients receiving lubiprostone 8 microg twice daily for 3 months than in those receiving placebo. In addition, a randomized, 4-week withdrawal period at the end of one of the phase III trials demonstrated that discontinuation of lubiprostone was not associated with rebound of IBS symptoms. Lubiprostone was generally well tolerated in clinical trials, with the majority of adverse events being of mild to moderate severity. In patients with IBS-C who received lubiprostone 8 microg twice daily, nausea was the most frequently occurring adverse event that was considered possibly or probably treatment related. No serious treatment-related adverse events were reported in a 36-week open-label extension to the phase III trials.

N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review

PubMed Central

Oliver, Georgina; Dean, Olivia; Camfield, David; Blair-West, Scott; Ng, Chee; Berk, Michael; Sarris, Jerome

2015-01-01

Objective Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area. Methods PubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders. Researchers with known involvement in NAC studies were contacted for any unpublished data. Results Four clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400–3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation. Conclusion Encouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research. PMID:25912534

Randomized control trial of computer-based training targeting alertness in older adults: the ALERT trial protocol.

PubMed

VanVleet, Thomas; Voss, Michelle; Dabit, Sawsan; Mitko, Alex; DeGutis, Joseph

2018-05-03

Healthy aging is associated with a decline in multiple functional domains including perception, attention, short and long-term memory, reasoning, decision-making, as well as cognitive and motor control functions; all of which are significantly modulated by an individual's level of alertness. The control of alertness also significantly declines with age and contributes to increased lapses of attention in everyday life, ranging from minor memory slips to a lack of vigilance and increased risk of falls or motor-vehicle accidents. Several experimental behavioral therapies designed to remediate age-related cognitive decline have been developed, but differ widely in content, method and dose. Preliminary studies demonstrate that Tonic and Phasic Alertness Training (TAPAT) can improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments. The purpose of the current trial (referred to as the Attention training for Learning Enhancement and Resilience Trial or ALERT) is to compare TAPAT to an active control training condition, include a larger sample of patients, and assess both cognitive and functional outcomes. We will employ a multi-site, longitudinal, blinded randomized controlled trial (RCT) design with a target sample of 120 patients with age-related cognitive decline. Patients will be asked to complete 36 training sessions remotely (30 min/day, 5 days a week, over 3 months) of either the experimental TAPAT training program or an active control computer games condition. Patients will be assessed on a battery of cognitive and functional outcomes at four time points, including: a) immediately before training, b) halfway through training, c) within forty-eight hours post completion of total training, and d) after a three-month no-contact period post completion of total training, to assess the longevity of potential training effects. The strengths of this protocol are that it tests an innovative, in-home administered treatment that targets a fundamental deficit in adults with age-related cognitive decline; employs highly sensitive computer-based assessments of cognition as well as functional abilities, and incorporates a large sample size in an RCT design. ClinicalTrials.gov identifier: NCT02416401.

Evaluation of a commercial Bacillus thuringiensis var. israelensis formulation for the control of chironomid midge larvae (Diptera: Chironomidae) in establishing rice crops in south-eastern Australia.

PubMed

Stevens, Mark M; Hughes, Peter A; Mo, Jianhua

2013-01-01

A commercial formulation of Bacillus thuringiensis var. israelensis (B.t.i.) was evaluated for its potential to control chironomid midge larvae in newly sown rice crops in south-eastern Australia. Two replicated small-plot field trials were conducted using product application rates of 0.5-6 kg/ha. In trial 1 application rates between 2 and 6 kg product/ha all significantly (P<0.05) reduced populations of target Chironominae/Orthocladiinae by between 71% and 93% over the 19 day post-treatment monitoring period. Trial 2 was conducted using lower application rates (0.5-2 kg product/ha) and only the 2 kg product/ha rate significantly (P<0.05) reduced numbers of the target group (81% reduction) despite lower application rates resulting in target group suppression of 38-62%. Identification of larvae to species level from selected samples indicated that populations of Chironomus tepperi, the principal pest species that attacks the roots of rice seedlings, were reduced at all application rates; elimination of C. tepperi was achieved in trial 1 at an application rate of 2 kg/ha. Consistent with other studies, non-target Tanypodinae were not adversely affected by B.t.i., and in some treatments populations of Tanypodinae exceeded control levels by up to 73%. In the first trial, which was conducted under relatively high pest pressure, plant establishment was significantly (P<0.05) increased (120-157%) by Vectobac® WDG application rates of 2-6 kg/ha. No significant increase in plant establishment relative to the controls was identified in the second trial, when pest pressure was substantially lower and minimal damage occurred in the control bays. Overall, our results demonstrate that B.t.i. may be an economically viable alternative to broad-spectrum synthetic pesticides for the control of phytophagous midge larvae in establishing rice crops where members of the Chironominae, the group most susceptible to B.t.i., are the principal species of concern. The high specificity of B.t.i. for nematoceran Diptera should lead to reduced impacts on non-target organisms. Copyright © 2012 Elsevier Inc. All rights reserved.

Balloon dilation of the eustachian tube for dilatory dysfunction: A randomized controlled trial.

PubMed

Poe, Dennis; Anand, Vijay; Dean, Marc; Roberts, William H; Stolovitzky, Jose Pablo; Hoffmann, Karen; Nachlas, Nathan E; Light, Joshua P; Widick, Mark H; Sugrue, John P; Elliott, C Layton; Rosenberg, Seth I; Guillory, Paul; Brown, Neil; Syms, Charles A; Hilton, Christopher W; McElveen, John T; Singh, Ameet; Weiss, Raymond L; Arriaga, Moises A; Leopold, John P

2018-05-01

To assess balloon dilation of the Eustachian tube with Eustachian tube balloon catheter in conjunction with medical management as treatment for Eustachian tube dilatory dysfunction. In this prospective, multicenter, randomized, controlled trial, we assigned, in a 2:1 ratio, patients age 22 years and older with Eustachian tube dilatory dysfunction refractory to medical therapy to undergo balloon dilation of the Eustachian tube with balloon catheter in conjunction with medical management or medical management alone. The primary endpoint was normalization of tympanogram at 6 weeks. Additional endpoints were normalization of Eustachian Tube Dysfunction Questionaire-7 symptom scores, positive Valsalva maneuver, mucosal inflammation, and safety. Primary efficacy results demonstrated superiority of balloon dilation of the Eustachian tube with balloon catheter + medical management compared to medical management alone. Tympanogram normalization at 6-week follow-up was observed in 51.8% (72/139) of investigational patients versus 13.9% (10/72) of controls (P < .0001). Tympanogram normalization in the treatment group was 62.2% after 24 weeks. Normalization of Eustachian Tube Dysfunction Questionaire-7 Symptom scores at 6-week follow-up was observed in 56.2% (77/137) of investigational patients versus 8.5% (6/71) controls (P < .001). The investigational group also demonstrated substantial improvement in both mucosal inflammation and Valsalva maneuver at 6-week follow-up compared to controls. No device- or procedure-related serious adverse events were reported for those who underwent balloon dilation of the Eustachian tube. This study demonstrated superiority of balloon dilation of the Eustachian tube with balloon catheter + medical management compared to medical management alone to treat Eustachian tube dilatory dysfunction in adults. 1b. Laryngoscope, 128:1200-1206, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Night glucose control with MD-Logic artificial pancreas in home setting: a single blind, randomized crossover trial-interim analysis.

PubMed

Nimri, Revital; Muller, Ido; Atlas, Eran; Miller, Shahar; Kordonouri, Olga; Bratina, Natasa; Tsioli, Christiana; Stefanija, Magdalena A; Danne, Thomas; Battelino, Tadej; Phillip, Moshe

2014-03-01

Artificial pancreas (AP) systems have shown an improvement in glucose control and a reduced risk of nocturnal hypoglycemia under controlled conditions but remain to be evaluated under daily-life conditions. To assess the feasibility, safety, and efficacy of the MD-Logic AP in controlling nocturnal glucose levels in the patient's home. Two-arm study, each covering four consecutive nights comparing the MD-Logic AP ('closed-loop' arm) with sensor-augmented pump therapy ('control' arm). Fifteen patients (mean age 19 ± 10.4 yr, A1c 7.5 ± 0.5% or 58 ± 5.9 mmol/mol, diabetes duration 9.9 ± 8.2 yr) were randomly assigned either to 'Group A' (first 'closed-loop', then 'control' arm) or to 'Group B' (vice versa). Investigators were masked to treatment intervention. Primary endpoints were the time spent with glucose levels below 70 mg/dL and the percentage of nights in which the mean overnight glucose levels were within 90-140 mg/dL. Endpoint analyses were based on unmodified sensor glucose readings of the four study nights. Time of glucose levels spent below 70 mg/dL was significantly shorter on the closed-loop nights than on control nights, median and interquartile range 3.8 (0, 11.6) and 48.7 (0.6, 67.9) min, respectively; p = 0.0034. The percentage of individual nights in which mean overnight glucose level was within 90-140 mg/dL was 67 (33, 88), and 50 (25, 75), under closed-loop and control nights, respectively, with no statistical difference. Secondary endpoint analyses demonstrated significant improvements in hypoglycemia parameters. No serious adverse events were reported. This interim analysis demonstrates the feasibility, safety, and efficiency of the MD-Logic AP system in home use, and demonstrates an improvement over sensor-augmented pump therapy. (ClinicalTrials.gov identifier NCT01726829). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Water-saving impacts of Smart Meter technology: An empirical 5 year, whole-of-community study in Sydney, Australia

NASA Astrophysics Data System (ADS)

Davies, Kirsten; Doolan, Corinna; van den Honert, Robin; Shi, Rose

2014-09-01

In 2009-2010 Sydney Water, the primary water utility in Sydney, conducted a comprehensive Smart Metering trial in residential homes in the suburb of Westleigh, in Sydney's north. The trial involved 1923 participants residing in 630 households. A whole-of-community method of engagement was applied to capture the views of residents from 12 to 70+ years of age. The trial examined the effects of the technology on the water consumption of an intervention group compared with that of a matched control group. After removing properties that had been sold since the beginning of the trial, properties in the study group were matched with a control group property on the basis of the household size, property size and the presence (or otherwise) of a swimming pool. The effects of the technology on consumption were measured and analyzed for the period July 2009 to June 2010, coupled with qualitative information that was collected throughout the duration of the study. A key finding was that households with the in-home display (IHD) installed, reduced their consumption by an average of over 6.8% over the study period when compared to the control group. Since completion of the study the community has not had any further interventions. The trial created an opportunity to examine the longer-term effects of the technology (June 2008 to September 2013). Consumption data collected over the 3 year posttrial period revealed that the participant group consumed 6.4% per month less water when compared to the pretrial period, whilst the matched control group consumed 1.3% per month more water when compared to the pretrial period. The reduced consumption of the participant group was maintained over time, demonstrating the long-term value of this technology.

Breakingtheice: A protocol for a randomised controlled trial of an internet-based intervention addressing amphetamine-type stimulant use

PubMed Central

2012-01-01

Background The prevalence of amphetamine-type stimulant use is greater than that of opioids and cocaine combined. Currently, there are no approved pharmacotherapy treatments for amphetamine-type stimulant problems, but some face-to-face psychotherapies are of demonstrated effectiveness. However, most treatment services focus on alcohol or opioid disorders, have limited reach and may not appeal to users of amphetamine-type stimulants. Internet interventions have proven to be effective for some substance use problems but none has specifically targeted users of amphetamine-type stimulants. Design/method The study will use a randomized controlled trial design to evaluate the effect of an internet intervention for amphetamine-type stimulant problems compared with a waitlist control group. The primary outcome will be assessed as amphetamine-type stimulant use (baseline, 3 and 6 months). Other outcomes measures will include ‘readiness to change’, quality of life, psychological distress (K-10 score), days out of role, poly-drug use, help-seeking intention and help-seeking behavior. The intervention consists of three modules requiring an estimated total completion time of 90 minutes. The content of the modules was adapted from face-to-face clinical techniques based on cognitive behavior therapy and motivation enhancement. The target sample is 160 men and women aged 18 and over who have used amphetamine-type stimulants in the last 3 months. Discussion To our knowledge this will be the first randomized controlled trial of an internet intervention specifically developed for users of amphetamine-type stimulants. If successful, the intervention will offer greater reach than conventional therapies and may engage clients who do not generally seek treatment from existing service providers. Trial registration Australian and New Zealand Clinical Trials Registry (www.anzctr.org.au/) ACTRN12611000947909 PMID:22731926

Cognitive-behavioral therapy for somatization and symptom syndromes: a critical review of controlled clinical trials.

PubMed

Kroenke, K; Swindle, R

2000-01-01

Few treatments for somatization have been proven effective. In the past decade, however, clinical trials of cognitive-behavioral therapy (CBT) have been promising. Our aim was to critically review and synthesize the evidence from these trials. A search of the Medline database from 1966 through July 1999 was conducted to identify controlled trials designed to evaluate the efficacy of CBT in patients with somatization or symptom syndromes. A total of 31 controlled trials (29 randomized and 2 nonrandomized) were identified. Twenty-five studies targeted a specific syndrome (e.g. chronic fatigue, irritable bowel, pain) while 6 focused on more general somatization or hypochondriasis. Primary outcome assessment included physical symptoms, psychological distress and functional status in 28, 26 and 19 studies, respectively. Physical symptoms appeared the most responsive: CBT-treated patients improved more than control subjects in 71% of the studies and showed possibly greater improvement (i.e., a trend) in another 11% of the studies. A definite or possible advantage of CBT for reducing psychological distress was demonstrated in only 38 and 8% of studies, and for improving functional status in 47 and 26%. Group therapy and interventions as brief as 5 sessions proved efficacious. Benefits were sustained for up to 12 months. CBT can be an effective treatment for patients with somatization or symptom syndromes. Benefits can occur whether or not psychological distress is ameliorated. Since chronic symptoms are exceptionally common and most studies were conducted in referral populations, the optimal sequencing of CBT in treating primary care patients and the identification of those most likely to accept and respond to therapy should be further evaluated. Copyright 2000 S. Karger AG, Basel.

Consumers' salient beliefs regarding dairy products in the functional food era: a qualitative study using concepts from the theory of planned behaviour.

PubMed

Nolan-Clark, Deborah J; Neale, Elizabeth P; Probst, Yasmine C; Charlton, Karen E; Tapsell, Linda C

2011-11-03

Inadequate consumption of dairy products without appropriate dietary substitution may have deleterious health consequences. Social research reveals the factors that may impede compliance with dietary recommendations. This is particularly important given the recent introduction of functional dairy products. One of the challenges for public health professionals is to demonstrate the efficacy of nutrition education in improving attitudes toward nutrient rich foods. The aim of this study was to explore the salient beliefs of adult weight loss trial participants regarding both traditional and functional dairy products and to compare these with a control group not exposed to nutrition education. Six focus groups were conducted, three with weight loss trial completers (n = 15) that had received nutrition education and three with individuals from the same region (n = 14) to act as controls. Transcribed focus groups were coded using the Theory of Planned Behaviour theoretical framework. Non-trial participants perceived dairy foods as weight inducing and were sceptical of functional dairy products. A lack of time/ability to decipher dairy food labels was also discussed by these individuals. In contrast trial participants discussed several health benefits related to dairy foods, practised label reading and were confident in their ability to incorporate dairy foods into their diet. Normative beliefs expressed were similar for both groups indicating that these were more static and less amenable to change through nutrition education than control and behavioural beliefs. Nutrition education provided as a result of weight loss trial participation influenced behavioural and control beliefs relating to dairy products. This study provides a proof of concept indication that nutrition education may improve attitudes towards dairy products and may thus be an important target for public health campaigns seeking to increase intake of this food group.

The effect of ondansetron, a 5-HT3 receptor antagonist, in chronic fatigue syndrome: a randomized controlled trial.

PubMed

The, Gerard K H; Bleijenberg, Gijs; Buitelaar, Jan K; van der Meer, Jos W M

2010-05-01

Accumulating data support the involvement of the serotonin (5-hydroxytryptamine [5-HT]) system in the pathophysiology of chronic fatigue syndrome. Neuropharmacologic studies point to a hyperactive 5-HT system, and open-label treatment studies with 5-HT(3) receptor antagonists have shown promising results. In this randomized controlled clinical trial, the effect of ondansetron, a 5-HT(3) receptor antagonist, was assessed on fatigue severity and functional impairment in adult patients with chronic fatigue syndrome. A randomized, placebo-controlled, double-blind clinical trial was conducted at Radboud University Nijmegen Medical Centre, The Netherlands. Sixty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome and who were free from current psychiatric comorbidity participated in the clinical trial. Participants received either ondansetron 16 mg per day or placebo for 10 weeks. The primary outcome variables were fatigue severity (Checklist Individual Strength fatigue severity subscale [CIS-fatigue]) and functional impairment (Sickness Impact Profile-8 [SIP-8]). The effect of ondansetron was assessed by analysis of covariance. Data were analyzed on an intention-to-treat basis. All patients were recruited between June 2003 and March 2006. Thirty-three patients were allocated to the ondansetron condition, 34 to the placebo condition. The 2 groups were well matched in terms of age, sex, fatigue severity, functional impairment, and CDC symptoms. Analysis of covariance showed no significant differences between the ondansetron- and placebo-treated groups during the 10-week treatment period in fatigue severity and functional impairment. This clinical trial demonstrates no benefit of ondansetron compared to placebo in the treatment of chronic fatigue syndrome. www.trialregister.nl: ISRCTN02536681. ©Copyright 2010 Physicians Postgraduate Press, Inc.

Pilot and Repeat Trials as Development Tools Associated with Demonstration of Bioequivalence.

PubMed

Fuglsang, Anders

2015-05-01

The purpose of this work is to use simulated trials to study how pilot trials can be implemented in relation to bioequivalence testing, and how the use of the information obtained at the pilot stage can influence the overall chance of showing bioequivalence (power) or the chance of approving a truly bioinequivalent product (type I error). The work also covers the use of repeat pivotal trials since the difference between a pilot trial followed by a pivotal trial and a pivotal trial followed by a repeat trial is mainly a question of whether a conclusion of bioequivalence can be allowed after the first trial. Repeating a pivotal trial after a failed trial involves dual or serial testing of the bioequivalence null hypothesis, and the paper illustrates how this may inflate the type I error up to almost 10%. Hence, it is questioned if such practice is in the interest of patients. Tables for power, type I error, and sample sizes are provided for a total of six different decision trees which allow the developer to use either the observed geometric mean ratio (GMR) from the first or trial or to assume that the GMR is 0.95. In cases when the true GMR can be controlled so as not to deviate more from unity than 0.95, sequential design methods ad modum Potvin may be superior to pilot trials. The tables provide a quantitative basis for choosing between sequential designs and pivotal trials preceded by pilot trials.

Toxoplasma gondii and schizophrenia: a review of published RCTs.

PubMed

Chorlton, Sam D

2017-07-01

Over the last 60 years, accumulating evidence has suggested that acute, chronic, and maternal Toxoplasma gondii infections predispose to schizophrenia. More recent evidence suggests that chronically infected patients with schizophrenia present with more severe disease. After acute infection, parasites form walled cysts in the brain, leading to lifelong chronic infection and drug resistance to commonly used antiparasitics. Chronic infection is the most studied and closely linked with development and severity of schizophrenia. There are currently four published randomized controlled trials evaluating antiparasitic drugs, specifically azithromycin, trimethoprim, artemisinin, and artemether, in patients with schizophrenia. No trials have demonstrated a change in psychopathology with adjunctive treatment. Published trials have either selected drugs without evidence against chronic infection or used them at doses too low to reduce brain cyst burden. Furthermore, trials have failed to achieve sufficient power or account for confounders such as previous antipsychotic treatment, sex, age, or rhesus status on antiparasitic effect. There are currently no ongoing trials of anti-Toxoplasma therapy in schizophrenia despite ample evidence to justify further testing.

Smartphone application for multi-phasic interventional trials in psychiatry: Technical design of a smart server.

PubMed

Zhang, Melvyn W B; Ho, Roger C M

2017-01-01

Smartphones and their accompanying applications are currently widely utilized in various healthcare interventions. Prior to the deployment of these tools for healthcare intervention, typically, proof of concept feasibility studies, as well as randomized trials are conducted to determine that these tools are efficacious prior to their actual implementation. In the field of psychiatry, most of the current interventions seek to compare smartphone based intervention against conventional care. There remains a paucity of research evaluating different forms of interventions using a single smartphone application. In the field of nutrition, there has been recent pioneering research demonstrating how a multi-phasic randomized controlled trial could be conducted using a single smartphone application. Despite the innovativeness of the previous smartphone conceptualization, there remains a paucity of technical information underlying the conceptualization that would support a multi-phasic interventional trial. It is thus the aim of the current technical note to share insights into an innovative server design that would enable the delivery of multi-phasic trials.

Fallibility: a new perspective on the ethics of clinical trial enrollment.

PubMed

Shamy, Michel C F; Stahnisch, Frank W; Hill, Michael D

2015-01-01

The ethical principle of 'equipoise', introduced in 1974, represents the most widely influential justification for the enrollment of patients into randomized clinical trials. However, definitions of equipoise vary, and its terms are not universally accepted. In this paper, we suggest a new way of approaching the ethics of clinical trial enrollment, which we call fallibility. The principle of fallibility argues that all physician opinions are sufficiently uncertain to warrant investigation, and that the ethical justification for any trial becomes a question of its epistemic validity, by which we mean the strength of its hypotheses and methods. The principle of fallibility can be translated into practice through the virtues of humility, skepticism and caring. While we cite recent examples from stroke medicine to demonstrate the limitations of equipoise, we propose that fallibility may offer a more general means of addressing the controversies that arise surrounding randomized controlled trials in many disciplines of medicine. © 2014 World Stroke Organization.

A cluster-randomized effectiveness trial of a physician-pharmacist collaborative model to improve blood pressure control.

PubMed

Carter, Barry L; Clarke, William; Ardery, Gail; Weber, Cynthia A; James, Paul A; Vander Weg, Mark; Chrischilles, Elizabeth A; Vaughn, Thomas; Egan, Brent M

2010-07-01

Numerous studies have demonstrated the value of team-based care to improve blood pressure (BP) control, but there is limited information on whether these models would be adopted in diverse populations. The purpose of this study was to evaluate whether a collaborative model between physicians and pharmacists can improve BP control in multiple primary care medical offices with diverse geographic and patient characteristics and whether long-term BP control can be sustained. This study is a randomized prospective trial in 27 primary care offices first stratified by the percentage of underrepresented minorities and the level of clinical pharmacy services within the office. Each office is then randomized to either a 9- or 24-month intervention or a control group. Patients will be enrolled in this study until 2012. The results of this study should provide information on whether this model can be implemented in large numbers of diverse offices, if it is effective in diverse populations, and whether BP control can be sustained long term. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00935077.

Dialectical Behaviour Therapy: Description, Research and Future Directions

ERIC Educational Resources Information Center

Swales, Michaela A.

2009-01-01

Dialectical Behaviour Therapy (DBT) is a cognitive behavioural treatment initially developed for adult women with a diagnosis of borderline personality disorder (BPD) and a history of chronic suicidal behaviour (Linehan, 1993a; 1993b). DBT was the first treatment for BPD to demonstrate its efficacy in a randomised controlled trial (Linehan ,…

Hibiscus sabdariffa L. tea (tisane) lowers blood pressure in prehypertensive and mildly hypertensive adults: a randomized, placebo-controlled clinical trial

USDA-ARS?s Scientific Manuscript database

Background: In vitro studies have shown Hibiscus sabdariffa L., an ingredient found in many herbal tea blends and other beverages, has antioxidant properties, and, in animal models, extracts of its calyces have demonstrated hypocholesterolemic and anti-hypertensive properties. Objective: To exa...

Self-Management Education for Rehabilitation Inpatients Suffering from Inflammatory Bowel Disease: A Cluster-Randomized Controlled Trial

ERIC Educational Resources Information Center

Reusch, A.; Weiland, R.; Gerlich, C.; Dreger, K.; Derra, C.; Mainos, D.; Tuschhoff, T.; Berding, A.; Witte, C.; Kaltz, B.; Faller, H.

2016-01-01

Although inflammatory bowel disease (IBD) affects patients' psychological well-being, previous educational programs have failed to demonstrate effects on psychosocial outcomes and quality of life. Therefore, we developed a group-based psychoeducational program that combined provision of both medical information and psychological self-management…

Enhancing Women's Resistance to Sexual Coercion: A Randomized Controlled Trial of the DATE Program

ERIC Educational Resources Information Center

Simpson Rowe, Lorelei; Jouriles, Ernest N.; McDonald, Renee; Platt, Cora G.; Gomez, Gabriella S.

2012-01-01

Objective: Despite extensive efforts to develop sexual assault prevention programs for college women, few have been rigorously evaluated, and fewer have demonstrable effects on victimization. This study pilots the Dating Assertiveness Training Experience (DATE), designed to train young women in assertiveness skills for responding to sexual…

Electronic Continuing Education in the Health Professions: An Update on Evidence from RCTs

ERIC Educational Resources Information Center

Lam-Antoniades, Margarita; Ratnapalan, Savithiri; Tait, Gordon

2009-01-01

Introduction: Demonstrating the effectiveness of the rapidly expanding field of electronic continuing education (e-CE) has important implications for CE in the health professions. This study provides an update on evidence from randomized controlled trials (RCTs) assessing the effectiveness of e-CE in the health professions. Methods: A literature…

Promoting Healthy Weight among Children with Developmental Delays

ERIC Educational Resources Information Center

Natale, Ruby R.; Camejo, Stephanie T.; Asfour, Lila; Uhlhorn, Susan B.; Delamater, Alan; Messiah, Sarah E.

2017-01-01

An extensive body of research demonstrates a higher prevalence of obesity among children with developmental delays (DD) versus children without delays. This analysis examined the effectiveness of a randomized controlled trial to promote healthy weight in a subsample of preschool-age children with DD (n = 71) on the adoption of quality nutrition…

Improving Middle-School Students' Knowledge and Comprehension in Social Studies: A Replication

ERIC Educational Resources Information Center

Vaughn, Sharon; Roberts, Greg; Swanson, Elizabeth A.; Wanzek, Jeanne; Fall, Anna-Mária; Stillman-Spisak, Stephanie J.

2015-01-01

This study aimed to replicate findings that demonstrated impact on students' reading comprehension and social studies content learning. Using a randomized control trial, intervention, and outcome measures, this study was replicated in 85 8th-grade social studies classes with 19 teachers. Teachers were provided professional development on…

Feasibility study of the effects of art as a creative engagement intervention during stroke rehabilitation on improvement of psychosocial outcomes: study protocol for a single blind randomized controlled trial: the ACES study.

PubMed

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

2014-09-28

Benefits of art participation after stroke are becoming increasingly recognized. Qualitative studies suggest that participation in visual arts creative engagement interventions (CEIs) during rehabilitation after stroke may improve mood, self-esteem, hope and some aspects of physical recovery. This study examines the feasibility of undertaking a randomized controlled trial of a CEI delivered by artists within in-patient stroke rehabilitation to test effectiveness. This trial is a two arm, single-blind, randomized controlled feasibility trial within in-patient stroke rehabilitation. We will recruit 80 patients receiving stroke rehabilitation in two stroke units in a health board area of Scotland (40 patients in each arm). Intervention arm participants will receive a visual-arts based CEI facilitated by experienced artists. Artists will follow an intervention protocol with specific components that enable participants to set, achieve and review artistic goals. Participants will receive up to eight intervention sessions, four within a group and four one-to-one with the artist. Control group participants will receive usual care only.Data collection will occur at baseline, post-intervention and three-month follow-up. Stroke-related health status is the primary outcome; mood, self-esteem, self-efficacy, perceived recovery control and hope are secondary outcomes. Semi-structured interviews will be conducted with purposively selected patients, artists and healthcare staff to elicit views and experiences of the intervention and feasibility and acceptability of trial processes. Recruitment rates, retention rates and patient preference for art participation will also be collected. Data will indicate, with confidence intervals, the proportion of patients choosing or refusing participation in the CEI and will allow calculation of recruitment rates for a future definitive trial. Summary data will indicate potential variability, magnitude and direction of difference between groups. Findings will inform sample size calculations for a definitive trial. Thematic analysis of qualitative data will be managed using the Framework Approach. Framework is an analytical approach for qualitative data, commonly used in policy and medical research. If shown to demonstrate effects, this intervention has the potential to address aspects of stroke recovery previously. Not routinely addressed in rehabilitation. Registered with Clinical Trials.Gov: NCT02085226 on 6th March 2014.

Aspirin for in vitro fertilisation.

PubMed

Siristatidis, Charalambos S; Dodd, Susanna R; Drakeley, Andrew J

2011-08-10

Aspirin is used to improve the outcome in women undergoing in vitro fertilisation despite inconsistent evidence of its efficacy. The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is an update of the review first published in 2007. To determine the effectiveness and safety of aspirin for improving the outcome of in vitro fertilisation and intracytoplasmic sperm injection treatment cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library January 2011), MEDLINE (1966 to January 2011) and EMBASE (1980 to January 2011) databases. We used the research terms: "(aspirin OR acetylsalicylic acid) AND (in-vitro fertilisation OR intracytoplasmic sperm injection)", combined with the Cochrane Menstrual Disorders and Subfertility Group's search strategy, in order to identify randomised controlled trials on aspirin for women undergoing in vitro fertilisation. Randomised controlled trials. Two authors independently selected studies to include in the review, extracted data and assessed trial quality. The searches identified 13 trials which were eligible for inclusion in the review, including a total of 2653 participants. No significant differences were found between the treatment and control groups for any of the outcomes assessed. No significant differences were found in the meta-analysis of studies investigating the effect of aspirin compared with control on live birth rate (RR 0.91, 95% CI 0.72 to 1.15; three studies and 1053 participants), clinical pregnancy rate (RR 1.03, 95% CI 0.91 to 1.17; 10 studies and 2142 participants), ectopic and miscarriage rates (RR 1.86, 95% CI 0.75 to 4.63; RR 1.10, 95% CI 0.68 to 1.77) respectively (three and five studies involving 1135 and 1497 participants). Use of aspirin for women undergoing in vitro fertilisation cannot be recommended due to lack of evidence from the current trial data. Adequately powered trials are needed. It was proposed in the initial version of this review that a sample size of 350 women in each group would be required in order to demonstrate a 10% improvement from the use of aspirin, with 80% power at the 5% significance level. Until such evidence is available, this treatment can not be recommended.

Role of antispasmodics in the treatment of irritable bowel syndrome

PubMed Central

Annaházi, Anita; Róka, Richárd; Rosztóczy, András; Wittmann, Tibor

2014-01-01

Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS. PMID:24876726

Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer-updated results.

PubMed

Kimura, Go; Ueda, Takeshi

2017-03-01

A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28-1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18-0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. © The Author 2016. Published by Oxford University Press.

Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer—updated results

PubMed Central

Ueda, Takeshi

2017-01-01

Abstract A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28–1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18–0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. PMID:28003320

High School Students With Reading Comprehension Difficulties: Results of a Randomized Control Trial of a Two-Year Reading Intervention.

PubMed

Vaughn, Sharon; Roberts, Greg; Wexler, Jade; Vaughn, Michael G; Fall, Anna-Mária; Schnakenberg, Jennifer B

2015-01-01

A 2-year, randomized control trial with 9th to 10th grade students with significant reading problems was provided for 50 minutes a day in small groups. Comparison students were provided an elective class and treatment students the reading intervention. Students were identified as demonstrating reading difficulties through failure on their state accountability test and were randomly assigned to one of three treatment conditions and a business as usual (BAU) condition: reading without dropout prevention, reading with dropout prevention, dropout prevention without reading, or a BAU condition. Findings from the 2-year reading intervention (reading with and without dropout prevention combined and BAU) are reported in this article. Students in reading treatment compared to students in BAU demonstrated significant gains on reading comprehension (effect size = .43), and improved reading was associated with better grades in social studies. Findings from this study provide a rationale for further implementation and investigation of intensive intervention for high school students with reading difficulties. © Hammill Institute on Disabilities 2014.

Monamine oxidase inhibitors: current and emerging agents for Parkinson disease.

PubMed

Fernandez, Hubert H; Chen, Jack J

2007-01-01

Monoamine oxidase type B (MAO-B) is the predominant isoform responsible for the metabolic breakdown of dopamine in the brain. Selective inhibition of brain MAO-B results in elevation of synaptosomal dopamine concentrations. Data have been reported regarding the selective MAO-B inhibitors, rasagiline and selegiline, for the symptomatic treatment of Parkinson disease (PD). Selegiline has demonstrated efficacy as monotherapy in patients with early PD (Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study), but evidence of selegiline efficacy as adjunctive treatment in levodopa-treated PD patients with motor fluctuations is equivocal. A new formulation of selegiline (Zydis selegiline) has been evaluated in 2 small, placebo-controlled studies as adjunctive therapy to levodopa. The Zydis formulation allows pregastric absorption of selegiline, minimizing first-pass metabolism, and thereby increasing selegiline bioavailability and reducing the concentration of amphetamine metabolites. Rasagiline is a selective, second-generation, irreversible MAO-B inhibitor, with at least 5 times the potency of selegiline in vitro and in animal models. Rasagiline has demonstrated efficacy in 1 large, randomized, double-blind, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease Outpatients) as initial monotherapy in patients with early PD, and in 2 large, controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off," Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily) as adjunctive treatment in levodopa-treated PD patients with motor fluctuations. Unlike selegiline, rasagiline is an aminoindan derivative with no amphetamine metabolites. A randomized clinical trial is underway to confirm preclinical and preliminary clinical data suggesting rasagiline has disease-modifying effects.

Consequences of Frequent Hemodialysis: Comparison to Conventional Hemodialysis and Transplantation

PubMed Central

Stokes, John B.

2011-01-01

The average life expectancy of a person on hemodialysis is less than 3 years and hasn't changed in 20 years. The Hemodialysis (HEMO) trial, a randomized trial to determine whether increasing urea removal to the maximum practical degree through a 3-times-a-week schedule, showed no difference in mortality in the treatment and control groups. Investigators speculated that the increment in functional waste removal in the HEMO study was too small to produce improvements in mortality. To test this hypothesis, the NIDDK funded the Frequent Hemodialysis Network, a consortium of centers testing whether patients randomized to intensive dialysis would demonstrate improved (reduced) left ventricular LV mass and quality of life. The trial has two arms: the daily (in-center) and the home (nocturnal) arms. Each arm has patients randomized to conventional dialysis or 6 days (or nights) of dialysis. The results of the HEMO trial will be reported in the fall of 2010. PMID:21686215

Toward phase 4 trials in heart failure: A social and corporate responsibility of the medical profession.

PubMed

Iyngkaran, Pupalan; Beneby, Glen S

2015-12-26

Congestive heart failure (CHF) is a chronic condition, requiring polypharmacy, allied health supports and regular monitoring. All these factors are needed to ensure compliance and to deliver the positive outcomes demonstrated from randomized controlled trials. Unfortunately many centers around the world are unable to match trial level support. The outcomes for many communities are thus unclear. Research design factors in post-marketing surveillance to address this issue. Phase 4 studies is the name given to trials designed to obtain such community level data and thus address issues of external validity. CHF phase 4 studies are relatively underutilized. We feel the onus for this research lies with the health profession. In this commentary we provide arguments as to why phase 4 studies should be viewed as a social and corporate responsibility of health professional that care for clients with CHF.

Unconsciously triggered conflict adaptation.

PubMed

van Gaal, Simon; Lamme, Victor A F; Ridderinkhof, K Richard

2010-07-09

In conflict tasks such as the Stroop, the Eriksen flanker or the Simon task, it is generally observed that the detection of conflict in the current trial reduces the impact of conflicting information in the subsequent trial; a phenomenon termed conflict adaptation. This higher-order cognitive control function has been assumed to be restricted to cases where conflict is experienced consciously. In the present experiment we manipulated the awareness of conflict-inducing stimuli in a metacontrast masking paradigm to directly test this assumption. Conflicting response tendencies were elicited either consciously (through primes that were weakly masked) or unconsciously (strongly masked primes). We demonstrate trial-by-trial conflict adaptation effects after conscious as well as unconscious conflict, which could not be explained by direct stimulus/response repetitions. These findings show that unconscious information can have a longer-lasting influence on our behavior than previously thought and further stretch the functional boundaries of unconscious cognition.

Unconsciously Triggered Conflict Adaptation

PubMed Central

van Gaal, Simon; Lamme, Victor A. F.; Ridderinkhof, K. Richard

2010-01-01

In conflict tasks such as the Stroop, the Eriksen flanker or the Simon task, it is generally observed that the detection of conflict in the current trial reduces the impact of conflicting information in the subsequent trial; a phenomenon termed conflict adaptation. This higher-order cognitive control function has been assumed to be restricted to cases where conflict is experienced consciously. In the present experiment we manipulated the awareness of conflict-inducing stimuli in a metacontrast masking paradigm to directly test this assumption. Conflicting response tendencies were elicited either consciously (through primes that were weakly masked) or unconsciously (strongly masked primes). We demonstrate trial-by-trial conflict adaptation effects after conscious as well as unconscious conflict, which could not be explained by direct stimulus/response repetitions. These findings show that unconscious information can have a longer-lasting influence on our behavior than previously thought and further stretch the functional boundaries of unconscious cognition. PMID:20634898

The Camino Verde intervention in Nicaragua, 2004-2012.

PubMed

Arosteguí, Jorge; Ledogar, Robert J; Coloma, Josefina; Hernández-Alvarez, Carlos; Suazo-Laguna, Harold; Cárcamo, Alvaro; Reyes, Rosa María; Belli, Alejandro; Andersson, Neil; Harris, Eva

2017-05-30

Camino Verde (the Green Way) is an evidence-based community mobilisation tool for prevention of dengue and other mosquito-borne viral diseases. Its effectiveness was demonstrated in a cluster-randomised controlled trial conducted in 2010-2013 in Nicaragua and Mexico. The Nicaraguan arm of the trial was preceded, from 2004 to 2008, by a feasibility study that provided valuable lessons and trained facilitators for the trial itself. Here, guided by the Template for Intervention Description and Replication (TIDieR), we describe the Camino Verde intervention in Nicaragua, presenting its rationale, its time and location, activities, materials used, the main actors, modes of delivery, how it was tailored to encourage community engagement, modifications made from the feasibility study to the trial itself, and how fidelity to the process originally designed was maintained. We also present information on costs and discuss the place of this study within the literature on implementation science. ISRCTN27581154 .

Toward phase 4 trials in heart failure: A social and corporate responsibility of the medical profession

PubMed Central

Iyngkaran, Pupalan; Beneby, Glen S

2015-01-01

Congestive heart failure (CHF) is a chronic condition, requiring polypharmacy, allied health supports and regular monitoring. All these factors are needed to ensure compliance and to deliver the positive outcomes demonstrated from randomized controlled trials. Unfortunately many centers around the world are unable to match trial level support. The outcomes for many communities are thus unclear. Research design factors in post-marketing surveillance to address this issue. Phase 4 studies is the name given to trials designed to obtain such community level data and thus address issues of external validity. CHF phase 4 studies are relatively underutilized. We feel the onus for this research lies with the health profession. In this commentary we provide arguments as to why phase 4 studies should be viewed as a social and corporate responsibility of health professional that care for clients with CHF. PMID:26713277

Systematic instruction for individuals with acquired brain injury: Results of a randomized controlled trial

PubMed Central

Powell, Laurie Ehlhardt; Glang, Ann; Ettel, Deborah; Todis, Bonnie; Sohlberg, McKay; Albin, Richard

2012-01-01

The goal of this study was to experimentally evaluate systematic instruction compared with trial-and-error learning (conventional instruction) applied to assistive technology for cognition (ATC), in a double blind, pretest-posttest, randomized controlled trial. Twenty-nine persons with moderate-severe cognitive impairments due to acquired brain injury (15 in systematic instruction group; 14 in conventional instruction) completed the study. Both groups received 12, 45-minute individual training sessions targeting selected skills on the Palm Tungsten E2 personal digital assistant (PDA). A criterion-based assessment of PDA skills was used to evaluate accuracy, fluency/efficiency, maintenance, and generalization of skills. There were no significant differences between groups at immediate posttest with regard to accuracy and fluency. However, significant differences emerged at 30-day follow-up in favor of systematic instruction. Furthermore, systematic instruction participants performed significantly better at immediate posttest generalizing trained PDA skills when interacting with people other than the instructor. These results demonstrate that systematic instruction applied to ATC results in better skill maintenance and generalization than trial-and-error learning for individuals with moderate-severe cognitive impairments due to acquired brain injury. Implications, study limitations, and directions for future research are discussed. PMID:22264146

Long-term insulin glargine therapy in type 2 diabetes mellitus: a focus on cardiovascular outcomes

PubMed Central

Joseph, Joshua J; Donner, Thomas W

2015-01-01

Cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus. Hyperinsulinemia is associated with increased cardiovascular risk, but the effects of exogenous insulin on cardiovascular disease progression have been less well studied. Insulin has been shown to have both cardioprotective and atherosclerosis-promoting effects in laboratory animal studies. Long-term clinical trials using insulin to attain improved diabetes control in younger type 1 and type 2 diabetes patients have shown improved cardiovascular outcomes. Shorter trials of intensive diabetes control with high insulin use in higher risk patients with type 2 diabetes have shown either no cardiovascular benefit or increased all cause and cardiovascular mortality. Glargine insulin is a basal insulin analog widely used to treat patients with type 1 and type 2 diabetes. This review focuses on the effects of glargine on cardiovascular outcomes. Glargine lowers triglycerides, leads to a modest weight gain, causes less hypoglycemia when compared with intermediate-acting insulin, and has a neutral effect on blood pressure. The Outcome Reduction With Initial Glargine Intervention (ORIGIN trial), a 6.2 year dedicated cardiovascular outcomes trial of glargine demonstrated no increased cardiovascular risk. PMID:25657589

The impact of a disease management program (COACH) on the attainment of better cardiovascular risk control in dyslipidaemic patients at primary care centres (The DISSEMINATE Study): a randomised controlled trial

PubMed Central

2012-01-01

Background To evaluate the efficacy of Counselling and Advisory Care for Health (COACH) programme in managing dyslipidaemia among primary care practices in Malaysia. This open-label, parallel, randomised controlled trial compared the COACH programme delivered by primary care physicians alone (PCP arm) and primary care physicians assisted by nurse educators (PCP-NE arm). Methods This was a multi-centre, open label, randomised trial of a disease management programme (COACH) among dyslipidaemic patients in 21 Malaysia primary care practices. The participating centres enrolled 297 treatment naïve subjects who had the primary diagnosis of dyslipidaemia; 149 were randomised to the COACH programme delivered by primary care physicians assisted by nurse educators (PCP-NE) and 148 to care provided by primary care physicians (PCP) alone. The primary efficacy endpoint was the mean percentage change from baseline LDL-C at week 24 between the 2 study arms. Secondary endpoints included mean percentage change from baseline of lipid profile (TC, LDL-C, HDL-C, TG, TC: HDL ratio), Framingham Cardiovascular Health Risk Score and absolute risk change from baseline in blood pressure parameters at week 24. The study also assessed the sustainability of programme efficacy at week 36. Results Both study arms demonstrated improvement in LDL-C from baseline. The least squares (LS) mean change from baseline LDL-C were −30.09% and −27.54% for PCP-NE and PCP respectively. The difference in mean change between groups was 2.55% (p=0.288), with a greater change seen in the PCP-NE arm. Similar observations were made between the study groups in relation to total cholesterol change at week 24. Significant difference in percentage change from baseline of HDL-C were observed between the PCP-NE and PCP groups, 3.01%, 95% CI 0.12-5.90, p=0.041, at week 24. There was no significant difference in lipid outcomes between 2 study groups at week 36 (12 weeks after the programme had ended). Conclusion Patients who received coaching and advice from primary care physicians (with or without the assistance by nurse educators) showed improvement in LDL-cholesterol. Disease management services delivered by PCP-NE demonstrated a trend towards add-on improvements in cholesterol control compared to care delivered by physicians alone; however, the improvements were not maintained when the services were withdrawn. Trial registration National Medical Research Registration (NMRR) Number: NMRR-08-287-1442 Trial Registration Number (ClinicalTrials.gov Identifier): NCT00708370 PMID:23046818

Prevalence and factors associated with use of placebo control groups in randomized controlled trials in psoriasis: a cross-sectional study.

PubMed

Katz, Kenneth A; Karlawish, Jason H; Chiang, David S; Bognet, Rachel A; Propert, Katherine J; Margolis, David J

2006-11-01

The ethics and science of using placebo control groups in clinical trials have been widely debated. Few studies, however, have examined factors associated with choice of control group. Our aim was to assess the prevalence of use of placebo controls in randomized controlled trials in psoriasis and to identify factors associated with use of placebo controls in these trials. This is a cross-sectional study of randomized controlled trials in psoriasis published from January 1, 2001 to December 20, 2005 and indexed in the Cochrane Central Register of Controlled Trials. We extracted data on types of control groups used, design issues (number of patients enrolled, primary end point), disease characteristics (psoriasis type and severity), and extrascientific issues (trial location, funding source, and year of publication). We used bivariable and multivariable logistic regression to determine factors associated with use of a placebo control group. Of 194 citations, 187 were available for review. One hundred thirty-five trials from 134 articles in 38 journals met inclusion criteria. Eighty-three trials (61.5%) enrolling 8171 subjects (41.7%) used active controls only, and 52 trials (38.5%) enrolling 11,406 subjects (58.3%) used placebo controls. Adjusted for trial location and funding source, trials significantly more likely to have used placebo controls included those conducted in the United States (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.45-13.68; P < .001) and those funded by pharmaceutical companies (OR, 2.61; 95% CI, 1.19-5.73; P = .02). Predicted frequencies of placebo use ranged from 77.6% (industry-funded, conducted trials in the United States) to 18.6% (non-industry-funded trials not conducted in the United States). Our searches may not have identified all published trials, and we did not have access to data from unpublished trials. Use of placebo controls has been more common in psoriasis trials conducted in the United States and funded by pharmaceutical companies. The findings suggest that ethical and scientific issues related to choice of control group in psoriasis trials are interpreted markedly differently depending on trial location and funding source.

Chewing gum for the treatment of postoperative nausea and vomiting: a pilot randomized controlled trial.

PubMed

Darvall, J N; Handscombe, M; Leslie, K

2017-01-01

A novel treatment, chewing gum, may be non-inferior to ondansetron in inhibiting postoperative nausea and vomiting (PONV) in female patients after laparoscopic or breast surgery. In this pilot study, we tested the feasibility of a large randomized controlled trial. We randomized 94 female patients undergoing laparoscopic or breast surgery to ondansetron 4 mg i.v. or chewing gum if PONV was experienced in the postanaesthesia care unit (PACU). The primary outcome was full resolution of PONV, with non-inferiority defined as a difference between groups of <15% in a per protocol analysis. Secondary outcomes were PACU stay duration, anti-emetic rescue use, and acceptability of anti-emetic treatment. The feasibility of implementing the protocol in a larger trial was assessed. Postoperative nausea and vomiting in the PACU occurred in 13 (28%) ondansetron patients and 15 (31%) chewing gum patients (P=0.75). Three chewing gum patients could not chew gum when they developed PONV. On a per protocol basis, full resolution of PONV occurred in five of 13 (39%) ondansetron vs nine of 12 (75%) chewing gum patients [risk difference 37% (6.3-67%), P=0.07]. There was no difference in secondary outcomes between groups. Recruitment was satisfactory, the protocol was acceptable to anaesthetists and nurses, and data collection was complete. In this pilot trial, chewing gum was not inferior to ondansetron for treatment of PONV after general anaesthesia for laparoscopic or breast surgery in female patients. Our findings demonstrate the feasibility of a larger, multicentred randomized controlled trial to investigate this novel therapy. Australian New Zealand Clinical Trials Registry: ACTRN12615001327572. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Intention to treat (ITT) analysis as reported in orthodontic randomized controlled trials-evaluations of methodology and recommendations for the accurate use of ITT analysis and handling dropouts.

PubMed

Bondemark, Lars; Abdulraheem, Salem

2017-10-21

To systematically evaluate in five orthodontic journals how many randomized controlled trials (RCTs) use intention to treat (ITT) analysis and to assess the methodological quality of the ITT analysis, and finally, to demonstrate in an academic way how outcomes can be affected when not implementing the ITT analysis. A search of the database, Medline, was performed via PubMed for publication type 'randomized controlled trial' published for each journal between 1 January 2013 and 30 April 2017. The five orthodontic journals assessed were the American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontics, European Journal of Orthodontics, Journal of Orthodontics, and Orthodontics and Craniofacial Research. Two independent reviewers assessed each RCT to determine whether the trial reported an ITT or not or if a per-protocol analysis was accomplished. The initial search generated 137 possible trials. After applying the inclusion and exclusion criteria, 90 RCTs were included and assessed. Seventeen out of 90 RCTs (18.9%) either reported an ITT analysis in the text and/or supported the ITT by flow diagrams or tables. However, six RCTs applied and reported the ITT analysis correctly, while the majority performed a per-protocol analysis instead. Nearly all the trials that applied the ITT analysis incorrectly analysed the results using a per-protocol analysis, and thus, overestimating the results and/or having a reduced sample size which then could produce a diminished statistical power. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

A modified Mediterranean dietary intervention for adults with major depression: Dietary protocol and feasibility data from the SMILES trial.

PubMed

Opie, Rachelle S; O'Neil, Adrienne; Jacka, Felice N; Pizzinga, Josephine; Itsiopoulos, Catherine

2017-04-19

The SMILES trial was the first randomized controlled trial (RCT) explicitly designed to evaluate a dietary intervention, conducted by qualified dietitians, for reducing depressive symptomatology in adults with clinical depression. Here we detail the development of the prescribed diet (modified Mediterranean diet (ModiMedDiet)) for individuals with major depressive disorders (MDDs) that was designed specifically for the SMILES trial. We also present data demonstrating the extent to which this intervention achieved improvements in diet quality. The ModiMedDiet was designed using a combination of existing dietary guidelines and scientific evidence from the emerging field of nutritional psychiatric epidemiology. Sixty-seven community dwelling individuals (Melbourne, Australia) aged 18 years or over, with current poor quality diets, and MDDs were enrolled into the SMILES trial. A retention rate of 93.9 and 73.5% was observed for the dietary intervention and social support control group, respectively. The dietary intervention (ModiMedDiet) consisted of seven individual nutrition counselling sessions delivered by a qualified dietitian. The control condition comprised a social support protocol matched to the same visit schedule and length. This manuscript details the first prescriptive individualized dietary intervention delivered by dietitians for adults with major depression. Significant improvements in dietary quality were observed among individuals randomized to the ModiMedDiet group. These dietary improvements were also found to be associated with changes in depressive symptoms. The ModiMedDiet, a novel and individually tailored intervention designed specifically for adults with major depression, can be effectively implemented in clinical practice to manage this highly prevalent and debilitating condition. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820. Registered 29 February 2012.

Effectivity of artrihpi irrigation for diabetic ulcer healing: A randomized controlled trial

NASA Astrophysics Data System (ADS)

Gayatri, Dewi; Asmorohadi, Aries; Dahlia, Debie

2018-02-01

The healing process of diabetic ulcer is often impeded by inflammation, infection, and decreased immune state. High pressure irrigation (10-15 psi) may be used to control the infection level. This research was designed to identify the effectiveness of artrihpi irrigation device towards diabetic ulcers in public hospitals in the Central Java. This research is a randomized control trial with cross over design. Sixty four subjects were selected using block randomization technique, and were divided into control and intervention group. The intervention was given in 6 days along with wound healing evaluation in every 3 days. The results demonstrated that there was a significant difference decrease scoring healing after treatment, even though the difference scoring healing between both groups was not statistically significant. However, it means difference was found that in the intervention artrihpi the wound healing was better than the spuit. These results illustrates the artrihpi may be solution of using high pressure irrigation to help healing process diabetic ulcers.

[Efficacy and safety of reduced osmolarity oral rehydration salts in treatment of dehydration in children with acute diarrhea--a multicenter, randomized, double blind clinical trial].

PubMed

Yang, Dao-Feng; Guo, Wei; Tian, De-Ying; Luo, Xiao-Ping; He, Yong-Wen; Dai, Yong-An; Xu, Hua-Lin

2007-04-01

To assess the efficacy and safety of reduced osmolarity oral rehydration salts (ROORS) in treatment of mild to moderate dehydration caused by acute diarrhea in children. A multicenter, randomized, double-blind, positive drug controlled clinical trial was conducted in 125 cases aged 1 to 17 years. These children with acute diarrhea and signs of dehydration were randomly assigned to receive either ROORS (trial group, n = 62) or oral rehydration salts II (ORS II) (control group, n = 63). The volume of intravenous infusion were recorded. The improvements of systemic symtoms and signs, diarrhea, dehydration and total scores were compared between the two groups. The adverse events and changes of electrolyte and other laboratory tests during treatment were also observed and analyzed. The overall effective rates in trial group and control group were 96.8% and 96.8%, respectively. The recovery of systemic symptoms, dehydration signs and diarrhea occurred in 96%, 97% and 78% patients in trial groups, and 96%, 98% and 85% patients in control group. The scores of symptoms and signs in both groups decreased significantly after treatment. All the above parameters and the number of cases who needed intravenous infusion (41 vs. 39) were not statistically different between two groups. However, the average volume of intravenously infused fluids in trial group was (450.98 +/- 183.07) ml, 24.5% less than that in the control group (597.30 +/- 343.37) ml (P < 0.05). The mean serum Na(+) concentration elevated from (137.48 +/- 4.55) mmol/L to (139.52 +/- 3.25) mmol/L (P < 0.01) in control group after treatment, but the change was not statistically significant in trail group. Serum K(+), Cl(-), HCO(3)(-) and other laboratory result did not change significantly after treatment. The total scores in both groups decreased obviously after treatment, but no significant difference was demonstrated between two groups (P > 0.05). A case in trial group had mild abdominal distention and recovered spontaneously. ROORS was shown to be effective and safe in the treatment of mild and moderate dehydration induced by acute diarrhea. Compared to ORS II, ROORS could decrease the intravenous supplement of fluid and lower the risk of hypernatremia.

Cognitive Behavior Therapy for Generalized Social Anxiety Disorder in Adolescents: A Randomized Controlled Trial

PubMed Central

Herbert, James D.; Gaudiano, Brandon A.; Rheingold, Alyssa A.; Moitra, Ethan; Myers, Valerie H.; Dalrymple, Kristy L.; Brandsma, Lynn L.

2010-01-01

Early identification and treatment of social anxiety disorder (SAD) is critical to prevent development of a chronic course of symptoms, persistent functional impairment, and progressive psychiatric comorbidity. A small but growing literature supports the effectiveness of cognitive behavior therapy (CBT) for anxiety disorders, including SAD, in adolescence. The present randomized controlled trial evaluated the efficacy of group vs. individual CBT for adolescents with generalized SAD in relation to an educational/supportive psychotherapy that did not contain specific CBT elements. All three treatments were associated with significant reductions in symptoms and functional impairment, and in improved social skills. No differences between treatments emerged on measures of symptoms, but the CBT conditions demonstrated greater gains on behavioral measures. The implications of the findings are discussed. PMID:18653310

Baking soda dentifrice and periodontal health: A review of the literature.

PubMed

Sabharwal, Amarpreet; Scannapieco, Frank A

2017-11-01

Mechanical disruption of dental biofilm is critical to maintain periodontal health. Baking soda-containing dentifrices have shown to be potential aids for improving gingival health and maintaining dental biofilm control. Evidence from classic and contemporary literature is reviewed and summarized in this review. In vitro and in vivo (animal and human, respectively) studies and clinical trials have been analyzed. Some clinical studies demonstrated the benefits of baking soda dentifrices in plaque and gingivitis reduction. Clinical trials with longer follow-up would be useful to confirm the impact of baking soda on gingival health. Regular dental biofilm control and adjunctive use of baking soda dentifrices in an otherwise healthy and compliant patient may provide success in maintenance of gingival health. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

Rheumatoid Arthritis and Cardiovascular Disease: Update on Treatment Issues

PubMed Central

Barbhaiya, Medha; Solomon, Daniel H.

2016-01-01

Purpose of review This review examines thresholds for treatment of traditional cardiovascular disease (CVD) risk factors among RA patients and whether RA-specific treatment modulates cardiovascular risk. Recent findings There are substantial data demonstrating an increased CVD risk among patients with RA. Both traditional CVD risk factors and inflammation contribute to this risk. Recent epidemiologic studies strengthen the case that aggressive immunosuppression with biologic DMARDs, such as TNF antagonists, is associated with a reduced risk of CVD events. However, to data, there are no randomized controlled trials published regarding the management of CVD in RA. Summary Epidemiologic evidence continues to accumulate regarding the relationship between the effects of traditional CVD risk factors and RA-specific treatments on CV outcomes in RA. The field needs randomized controlled trials to better guide management. PMID:23466960

Application of Balanced Scorecard in the Evaluation of a Complex Health System Intervention: 12 Months Post Intervention Findings from the BHOMA Intervention: A Cluster Randomised Trial in Zambia

PubMed Central

Mutale, Wilbroad; Stringer, Jeffrey; Chintu, Namwinga; Chilengi, Roma; Mwanamwenge, Margaret Tembo; Kasese, Nkatya; Balabanova, Dina; Spicer, Neil; Lewis, James; Ayles, Helen

2014-01-01

Introduction In many low income countries, the delivery of quality health services is hampered by health system-wide barriers which are often interlinked, however empirical evidence on how to assess the level and scope of these barriers is scarce. A balanced scorecard is a tool that allows for wider analysis of domains that are deemed important in achieving the overall vision of the health system. We present the quantitative results of the 12 months follow-up study applying the balanced scorecard approach in the BHOMA intervention with the aim of demonstrating the utility of the balanced scorecard in evaluating multiple building blocks in a trial setting. Methods The BHOMA is a cluster randomised trial that aims to strengthen the health system in three rural districts in Zambia. The intervention aims to improve clinical care quality by implementing practical tools that establish clear clinical care standards through intensive clinic implementations. This paper reports the findings of the follow-up health facility survey that was conducted after 12 months of intervention implementation. Comparisons were made between those facilities in the intervention and control sites. STATA version 12 was used for analysis. Results The study found significant mean differences between intervention(I) and control (C) sites in the following domains: Training domain (Mean I:C; 87.5.vs 61.1, mean difference 23.3, p = 0.031), adult clinical observation domain (mean I:C; 73.3 vs.58.0, mean difference 10.9, p = 0.02 ) and health information domain (mean I:C; 63.6 vs.56.1, mean difference 6.8, p = 0.01. There was no gender differences in adult service satisfaction. Governance and motivation scores did not differ between control and intervention sites. Conclusion This study demonstrates the utility of the balanced scorecard in assessing multiple elements of the health system. Using system wide approaches and triangulating data collection methods seems to be key to successful evaluation of such complex health intervention. Trial number ClinicalTrials.gov NCT01942278 PMID:24751780

Current status of atypical antipsychotics for the treatment of fibromyalgia.

PubMed

Rico-Villademoros, F; Calandre, E P; Slim, M

2014-06-01

The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms. Copyright 2014 Prous Science, S.A.U. or its licensors. All rights reserved.

Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes.

PubMed

Glujovsky, Demián; Pesce, Romina; Fiszbajn, Gabriel; Sueldo, Carlos; Hart, Roger J; Ciapponi, Agustín

2010-01-20

If a fresh embryo, assisted reproductive technology procedure cycle is unsuccessful and there are frozen embryos available, a frozen-thawed embryo transfer is performed. In some specific cases women may undergo oocyte donation treatment. In both situations the endometrium is primed by the administration of estrogen and progesterone. To prevent the possibility of spontaneous ovulation, gonadotropin-releasing hormone (GnRH) agonists are frequently used. To evaluate the most effective endometrial preparation for women undergoing transfer with frozen embryos or embryos from donor oocytes with regard to the subsequent live birth rate. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, and abstracts of reproductive societies' meetings (from inception). No language restrictions were applied. Experts in the field were contacted. Randomised controlled trials evaluating endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. Two review authors independently applied the inclusion criteria, assessed trial risk of bias, and extracted data. Twenty two randomised controlled trials were included. Five studies analysed the use of a GnRH agonist versus control. No significant benefit was demonstrated when using GnRH agonists. No evidence of statistically significant benefit was found for one GnRH agonist over another, or vaginal over intramuscular progesterone administration. No difference in pregnancy rate was demonstrated when no treatment was compared to aspirin, steroids, ovarian stimulation, or human chorionic gonadotropin (hCG) prior to embryo transfer, although using hCG several times before the oocyte retrieval decreases the pregnancy rate. Finally, when oocyte recipients were studied further, starting progesterone on the day of oocyte pick-up (OPU) or the day after OPU produced a significantly higher pregnancy rate (OR 1.87, 95% CI 1.13 to 3.08) than when recipients started progesterone the day prior to OPU. There is insufficient evidence to recommend any one particular protocol for endometrial preparation over another with regard to pregnancy rates after embryo transfers. These were either frozen embryos or embryos derived from donor oocytes. However, there is evidence of a lower pregnancy rate and a higher cycle cancellation rate when the progesterone supplementation is commenced prior to oocyte retrieval in oocyte donation cycles. Adequately powered studies are needed to evaluate each treatment more accurately.

Efficacy and safety of electroacupuncture with different acupoints for chemotherapy-induced nausea and vomiting: study protocol for a randomized controlled trial.

PubMed

Chen, Bo; Hu, Shu-xiang; Liu, Bao-hu; Zhao, Tian-yi; Li, Bo; Liu, Yan; Li, Ming-yue; Pan, Xing-fang; Guo, Yong-ming; Chen, Ze-lin; Guo, Yi

2015-05-12

Many patients experience nausea and vomiting during chemotherapy treatment. Evidence demonstrates that electroacupuncture is beneficial for controlling chemotherapy-induced nausea and vomiting (CINV). However, the acupoint or matching acupoint with the best efficacy for controlling CINV still remains unidentified. This study consists of a randomized controlled trial (RCT) with four parallel arms: a control group and three electroacupuncture groups (one with Neiguan (PC6), one with Zhongwan (CV12), and one with both PC6 and CV12). The control group received standard antiemetic only, while the other three groups received electroacupuncture stimulation with different acupoints besides the standard antiemetic. The intervention is done once daily from the first day (day 1) to the fourth day (day 4) during chemotherapy treatment. The primary outcome measures include frequency of nausea, vomiting and retching. The secondary outcome measures are the grade of constipation and diarrhea, electrogastrogram, assessment of quality of life, assessment of anxiety and depression, and other adverse effects during the chemotherapy. Assessments are scheduled from one day pre-chemotherapy (day 0) to the fifth day of chemotherapy (day 5). Follow-ups are done from day 6 to day 21. The aim of this study is to evaluate the efficacy and safety of electro-acupuncture with different acupoints in the management of CINV. The register number of randomized controlled trial is NCT02195908 . The date of registration was 21 July 2014.

Therapeutic Angiogenesis by Gene Therapy for Critical Limb Ischemia: Choice of Biological Agent.

PubMed

Sanada, Fumihiro; Taniyama, Yoshiaki; Azuma, Junya; Yuka, Ikeda-Iwabe; Kanbara, Yasuhiro; Iwabayashi, Masaaki; Rakugi, Hiromi; Morishita, Ryuichi

2014-04-01

Peripheral artery disease (PAD) is caused by atherosclerosis, hardening and narrowing arteries over time due to buildup of fatty deposit in vascular bed called plaque. Severe blockage of an artery of the lower extremity markedly reduce blood flow, resulting in critical limb ischemia (CLI) manifested by a variety of clinical syndromes including rest pain in the feet or toes, ulcer and gangrene with infection. Despite significant advances in clinical care and interventions for revascularization, patients with CLI remain at high risk for amputation and cardiovascular death. To overcome this unmet need, therapeutic angiogenesis using angiogenic growth factors has evolved in an attempt to increase blood flow in ischemic limb. Initial animal studies and phase I clinical trials with vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF) demonstrated promising results, inspiring scientists to progress forward. However, more rigorous phase II and III clinical trials have failed to demonstrate beneficial effects of these angiogenic growth factors to date. Recently, two multicenter, double-blind, placebo-controlled clinical trials in Japan (phase III) and US (phase II) demonstrated that hepatocyte growth factor (HGF) gene therapy for CLI significant improved primary end points and tissue oxygenation up to two years in comparison to placebo. These clinical results implicate a distinct action of HGF on cellular processes involved in vascular remodeling under pathological condition. This review presents data from phase I-III clinical trials of therapeutic angiogenesis by gene therapy in patients with PAD. Further, we discuss the potential explanation for the success or failure of clinical trials in the context of the biological mechanisms underlying angiogenesis and vascular remodeling, including cellular senescence, inflammation, and tissue fibrosis.

Increasing walking among older people: A test of behaviour change techniques using factorial randomised N-of-1 trials

PubMed Central

Nyman, Samuel R.; Goodwin, Kelly; Kwasnicka, Dominika; Callaway, Andrew

2016-01-01

Objective: Evaluations of techniques to promote physical activity usually adopt a randomised controlled trial (RCT). Such designs inform how a technique performs on average but cannot be used for treatment of individuals. Our objective was to conduct the first N-of-1 RCTs of behaviour change techniques with older people and test the effectiveness of the techniques for increasing walking within individuals. Design: Eight adults aged 60–87 were randomised to a 2 (goal-setting vs. active control) × 2 (self-monitoring vs. active control) factorial RCT over 62 days. The time series data were analysed for each single case using linear regressions. Main outcome measures: Walking was objectively measured using pedometers. Results: Compared to control days, goal-setting increased walking in 4 out of 8 individuals and self-monitoring increased walking in 7 out of 8 individuals. While the probability for self-monitoring to be effective in 7 out of 8 participants was beyond chance (p = .03), no intervention effect was significant for individual participants. Two participants had a significant but small linear decrease in walking over time. Conclusion: We demonstrate the utility of N-of-1 trials for advancing scientific enquiry of behaviour change and in practice for increasing older people’s physical activity. PMID:26387689

Are Anti-Stigma Films a Useful Strategy for Reducing Weight Bias Among Trainee Healthcare Professionals? Results of a Pilot Randomized Control Trial

PubMed Central

Swift, Judy Anne; Tischler, Victoria; Markham, Sophie; Gunning, Ingrid; Glazebrook, Cris; Beer, Charlotte; Puhl, Rebecca

2013-01-01

Background Weight bias is an important clinical issue that the educators of tomorrow's healthcare professionals cannot afford to ignore. This study, therefore, aimed to pilot a randomized controlled trial of the effects of educational films designed to reduce weight stigmatization toward obese patients on trainee dietitians’ and doctors’ attitudes. Methods A pre-post experimental design with a 6-week follow-up, which consisted of an intervention group (n = 22) and a control group (n = 21), was conducted to assess the efficacy of brief anti-stigma films in reducing weight bias, and to test whether future, larger-scale studies among trainee healthcare professionals are feasible. Results Participants at baseline demonstrated weight bias, on both implicit and explicit attitude measures, as well as strong beliefs that obesity is under a person's control. The intervention films significantly improved explicit attitudes and beliefs toward obese people, and participant evaluation was very positive. The intervention did not significantly improve implicit anti-fat bias. Conclusion The current study suggests both that it is possible to conduct a substantive trial of the effects of educational films designed to reduce weight stigma on a larger cohort of trainee healthcare professionals, and that brief educational interventions may be effective in reducing stigmatizing attitudes in this population. PMID:23466551

Are anti-stigma films a useful strategy for reducing weight bias among trainee healthcare professionals? Results of a pilot randomized control trial.

PubMed

Swift, Judy Anne; Tischler, Victoria; Markham, Sophie; Gunning, Ingrid; Glazebrook, Cris; Beer, Charlotte; Puhl, Rebecca

2013-01-01

Weight bias is an important clinical issue that the educators of tomorrow's healthcare professionals cannot afford to ignore. This study, therefore, aimed to pilot a randomized controlled trial of the effects of educational films designed to reduce weight stigmatization toward obese patients on trainee dietitians' and doctors' attitudes. A pre-post experimental design with a 6-week follow-up, which consisted of an intervention group (n = 22) and a control group (n = 21), was conducted to assess the efficacy of brief anti-stigma films in reducing weight bias, and to test whether future, larger-scale studies among trainee healthcare professionals are feasible. Participants at baseline demonstrated weight bias, on both implicit and explicit attitude measures, as well as strong beliefs that obesity is under a person's control. The intervention films significantly improved explicit attitudes and beliefs toward obese people, and participant evaluation was very positive. The intervention did not significantly improve implicit anti-fat bias. The current study suggests both that it is possible to conduct a substantive trial of the effects of educational films designed to reduce weight stigma on a larger cohort of trainee healthcare professionals, and that brief educational interventions may be effective in reducing stigmatizing attitudes in this population.

Endovascular Management of Atherosclerotic Renal Artery Stenosis: Post-Cardiovascular Outcomes in Renal Atherosclerotic Lesions Era Winner or False Alarm?

PubMed Central

Karanikola, Evridiki; Karaolanis, Georgios; Galyfos, George; Barbaressos, Emmanuel; Palla, Viktoria; Filis, Konstantinos

2017-01-01

Renal artery stenosis (RAS) is frequently associated with severe comorbidities such as reduced renal perfusion, hypertension, and end-stage renal failure. In approximately 90% of patients, renal artery atherosclerosis is the main cause for RAS, and it is associated with an increased risk for fatal and non-fatal cardiovascular and renal complications. Endovascular management of atherosclerotic RAS (ARAS) has been recently evaluated by several randomized controlled trials that failed to demonstrate benefit of stenting. Furthermore, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions study did not demonstrate any benefit over the revascularization approach. In this review, we summarized the available data from retrospective, prospective and randomized trials on ARAS to provide clinicians with sufficient data in order to produce useful conclusions for everyday clinical practice. PMID:28377906

A theory of eu-estrogenemia: a unifying concept

PubMed Central

Turner, Ralph J.; Kerber, Irwin J.

2017-01-01

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

Review of the role of probiotics in gastrointestinal diseases in adults.

PubMed

Sebastián Domingo, Juan José

Probiotics may act as biological agents that modify the intestinal microbiota and certain cytokine profiles, which can lead to an improvement in certain gastrointestinal diseases. To conduct a review of the evidence of the role of probiotics in certain gastrointestinal diseases in adults. Review conducted using appropriate descriptors, filters and limits in the PubMed database (MEDLINE). The MeSH terms used were Probiotics [in the title] AND Gastrointestinal Diseases, with the following limits or filters: Types of study: Systematic Reviews, Meta-Analysis, Guideline, Practice Guideline, Consensus Development Conference (and Consensus Development Conference NIH), Randomized Controlled Trial, Controlled Clinical Trial and Clinical Trial; age: adults (19 or older); language: English and Spanish; in humans, and with at least one abstract. Full texts of all the Systematic Reviews and meta-analyses directly related to the review's objective were obtained, as well as the Randomised Controlled Trials of the studies that were considered relevant and of sufficient quality for this review. Certain probiotics, different for each process, have proven to be effective and beneficial in cases of acute infectious diarrhoea, antibiotic-associated diarrhoea, Clostridium difficile-associated diarrhoea, pouchitis and Helicobacter pylori infection eradication. Although some probiotics have not demonstrated any benefit, there are certain gastrointestinal diseases in which the use of probiotics, true biological agents, can be recommended. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

CRITICAL REVIEW OF OUTCOME RESEARCH ON INTERPERSONAL PSYCHOTHERAPY FOR ANXIETY DISORDERS

PubMed Central

Markowitz, John C.; Lipsitz, Joshua; Milrod, Barbara L.

2014-01-01

Background Interpersonal psychotherapy (IPT) has demonstrated efficacy in treating mood and eating disorders. This article critically reviews outcome research testing IPT for anxiety disorders, a diagnostic area where cognitive behavioral therapy (CBT) has dominated research and treatment. Methods A literature search identified six open and five controlled trials of IPT for social anxiety disorder (SAD), panic disorder, and posttraumatic stress disorder. Results Studies were generally small, underpowered, and sometimes methodologically compromised. Nonetheless, minimally adapted from its standard depression strategies, IPT for anxiety disorders yielded positive results in open trials for the three diagnoses. In controlled trials, IPT fared better than waiting list (N = 2), was equipotent to supportive psychodynamic psychotherapy (N = 1), but less efficacious than CBT for SAD (N = 1), and CBT for panic disorder (N = 1) in a methodologically complicated study. IPT equaled CBT in a group residential format (N = 1). Conclusions IPT shows some promise for anxiety disorders but has thus far shown no advantages in controlled trials relative to other therapies. Methodological and ecological issues have complicated testing of IPT for anxiety disorders, clouding some findings. The authors discuss difficulties of conducting non-CBT research in a CBT-dominated area, investigator bias, and the probable need to further modify IPT for anxiety disorders. Untested therapies deserve the fairest possible testing. Depression and Anxiety 00:1–10, 2014. PMID:24493661

mHealth Intervention to Improve Diabetes Risk Behaviors in India: A Prospective, Parallel Group Cohort Study.

PubMed

Pfammatter, Angela; Spring, Bonnie; Saligram, Nalini; Davé, Raj; Gowda, Arun; Blais, Linelle; Arora, Monika; Ranjani, Harish; Ganda, Om; Hedeker, Donald; Reddy, Sethu; Ramalingam, Sandhya

2016-08-05

In low/middle income countries like India, diabetes is prevalent and health care access limited. Most adults have a mobile phone, creating potential for mHealth interventions to improve public health. To examine the feasibility and initial evidence of effectiveness of mDiabetes, a text messaging program to improve diabetes risk behaviors, a global nonprofit organization (Arogya World) implemented mDiabetes among one million Indian adults. A prospective, parallel cohort design was applied to examine whether mDiabetes improved fruit, vegetable, and fat intakes and exercise. Intervention participants were randomly selected from the one million Nokia subscribers who elected to opt in to mDiabetes. Control group participants were randomly selected from non-Nokia mobile phone subscribers. mDiabetes participants received 56 text messages in their choice of 12 languages over 6 months; control participants received no contact. Messages were designed to motivate improvement in diabetes risk behaviors and increase awareness about the causes and complications of diabetes. Participant health behaviors (exercise and fruit, vegetable, and fat intake) were assessed between 2012 and 2013 via telephone surveys by blinded assessors at baseline and 6 months later. Data were cleaned and analyzed in 2014 and 2015. 982 participants in the intervention group and 943 in the control group consented to take the phone survey at baselne. At the end of the 6-month period, 611 (62.22%) in the intervention and 632 (67.02%) in the control group completed the follow-up telephone survey. Participants receiving texts demonstrated greater improvement in a health behavior composite score over 6 months, compared with those who received no messages F(1, 1238) = 30.181, P<.001, 95% CI, 0.251-0.531. Fewer intervention participants demonstrated health behavior decline compared with controls. Improved fruit, vegetable, and fat consumption (P<.01) but not exercise were observed in those receiving messages, as compared with controls. A text messaging intervention was feasible and showed initial evidence of effectiveness in improving diabetes-related health behaviors, demonstrating the potential to facilitate population-level behavior change in a low/middle income country. Australian New Zealand Clinical Trials Registry (ACTRN): 12615000423516; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367946&isReview=true (Archived by WebCite at http://www.webcitation.org/6j5ptaJgF).

School-based interventions for preventing HIV, sexually transmitted infections, and pregnancy in adolescents.

PubMed

Mason-Jones, Amanda J; Sinclair, David; Mathews, Catherine; Kagee, Ashraf; Hillman, Alex; Lombard, Carl

2016-11-08

School-based sexual and reproductive health programmes are widely accepted as an approach to reducing high-risk sexual behaviour among adolescents. Many studies and systematic reviews have concentrated on measuring effects on knowledge or self-reported behaviour rather than biological outcomes, such as pregnancy or prevalence of sexually transmitted infections (STIs). To evaluate the effects of school-based sexual and reproductive health programmes on sexually transmitted infections (such as HIV, herpes simplex virus, and syphilis), and pregnancy among adolescents. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for published peer-reviewed journal articles; and ClinicalTrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform for prospective trials; AIDS Educaton and Global Information System (AEGIS) and National Library of Medicine (NLM) gateway for conference presentations; and the Centers for Disease Control and Prevention (CDC), UNAIDS, the WHO and the National Health Service (NHS) centre for Reviews and Dissemination (CRD) websites from 1990 to 7 April 2016. We handsearched the reference lists of all relevant papers. We included randomized controlled trials (RCTs), both individually randomized and cluster-randomized, that evaluated school-based programmes aimed at improving the sexual and reproductive health of adolescents. Two review authors independently assessed trials for inclusion, evaluated risk of bias, and extracted data. When appropriate, we obtained summary measures of treatment effect through a random-effects meta-analysis and we reported them using risk ratios (RR) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach. We included eight cluster-RCTs that enrolled 55,157 participants. Five trials were conducted in sub-Saharan Africa (Malawi, South Africa, Tanzania, Zimbabwe, and Kenya), one in Latin America (Chile), and two in Europe (England and Scotland). Sexual and reproductive health educational programmesSix trials evaluated school-based educational interventions.In these trials, the educational programmes evaluated had no demonstrable effect on the prevalence of HIV (RR 1.03, 95% CI 0.80 to 1.32, three trials; 14,163 participants; low certainty evidence), or other STIs (herpes simplex virus prevalence: RR 1.04, 95% CI 0.94 to 1.15; three trials, 17,445 participants; moderate certainty evidence; syphilis prevalence: RR 0.81, 95% CI 0.47 to 1.39; one trial, 6977 participants; low certainty evidence). There was also no apparent effect on the number of young women who were pregnant at the end of the trial (RR 0.99, 95% CI 0.84 to 1.16; three trials, 8280 participants; moderate certainty evidence). Material or monetary incentive-based programmes to promote school attendanceTwo trials evaluated incentive-based programmes to promote school attendance.In these two trials, the incentives used had no demonstrable effect on HIV prevalence (RR 1.23, 95% CI 0.51 to 2.96; two trials, 3805 participants; low certainty evidence). Compared to controls, the prevalence of herpes simplex virus infection was lower in young women receiving a monthly cash incentive to stay in school (RR 0.30, 95% CI 0.11 to 0.85), but not in young people given free school uniforms (Data not pooled, two trials, 7229 participants; very low certainty evidence). One trial evaluated the effects on syphilis and the prevalence was too low to detect or exclude effects confidently (RR 0.41, 95% CI 0.05 to 3.27; one trial, 1291 participants; very low certainty evidence). However, the number of young women who were pregnant at the end of the trial was lower among those who received incentives (RR 0.76, 95% CI 0.58 to 0.99; two trials, 4200 participants; low certainty evidence). Combined educational and incentive-based programmesThe single trial that evaluated free school uniforms also included a trial arm in which participants received both uniforms and a programme of sexual and reproductive education. In this trial arm herpes simplex virus infection was reduced (RR 0.82, 95% CI 0.68 to 0.99; one trial, 5899 participants; low certainty evidence), predominantly in young women, but no effect was detected for HIV or pregnancy (low certainty evidence). There is a continued need to provide health services to adolescents that include contraceptive choices and condoms and that involve them in the design of services. Schools may be a good place in which to provide these services. There is little evidence that educational curriculum-based programmes alone are effective in improving sexual and reproductive health outcomes for adolescents. Incentive-based interventions that focus on keeping young people in secondary school may reduce adolescent pregnancy but further trials are needed to confirm this.

Superior Inhibitory Control and Resistance to Mental Fatigue in Professional Road Cyclists.

PubMed

Martin, Kristy; Staiano, Walter; Menaspà, Paolo; Hennessey, Tom; Marcora, Samuele; Keegan, Richard; Thompson, Kevin G; Martin, David; Halson, Shona; Rattray, Ben

2016-01-01

Given the important role of the brain in regulating endurance performance, this comparative study sought to determine whether professional road cyclists have superior inhibitory control and resistance to mental fatigue compared to recreational road cyclists. After preliminary testing and familiarization, eleven professional and nine recreational road cyclists visited the lab on two occasions to complete a modified incongruent colour-word Stroop task (a cognitive task requiring inhibitory control) for 30 min (mental exertion condition), or an easy cognitive task for 10 min (control condition) in a randomized, counterbalanced cross-over order. After each cognitive task, participants completed a 20-min time trial on a cycle ergometer. During the time trial, heart rate, blood lactate concentration, and rating of perceived exertion (RPE) were recorded. The professional cyclists completed more correct responses during the Stroop task than the recreational cyclists (705±68 vs 576±74, p = 0.001). During the time trial, the recreational cyclists produced a lower mean power output in the mental exertion condition compared to the control condition (216±33 vs 226±25 W, p = 0.014). There was no difference between conditions for the professional cyclists (323±42 vs 326±35 W, p = 0.502). Heart rate, blood lactate concentration, and RPE were not significantly different between the mental exertion and control conditions in both groups. The professional cyclists exhibited superior performance during the Stroop task which is indicative of stronger inhibitory control than the recreational cyclists. The professional cyclists also displayed a greater resistance to the negative effects of mental fatigue as demonstrated by no significant differences in perception of effort and time trial performance between the mental exertion and control conditions. These findings suggest that inhibitory control and resistance to mental fatigue may contribute to successful road cycling performance. These psychobiological characteristics may be either genetic and/or developed through the training and lifestyle of professional road cyclists.

Trial Sequential Analysis in systematic reviews with meta-analysis.

PubMed

Wetterslev, Jørn; Jakobsen, Janus Christian; Gluud, Christian

2017-03-06

Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size. The results of the meta-analyses should relate the total number of randomised participants to the estimated required meta-analytic information size accounting for statistical diversity. When the number of participants and the corresponding number of trials in a meta-analysis are insufficient, the use of the traditional 95% confidence interval or the 5% statistical significance threshold will lead to too many false positive conclusions (type I errors) and too many false negative conclusions (type II errors). We developed a methodology for interpreting meta-analysis results, using generally accepted, valid evidence on how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached. The Lan-DeMets trial sequential monitoring boundaries in Trial Sequential Analysis offer adjusted confidence intervals and restricted thresholds for statistical significance when the diversity-adjusted required information size and the corresponding number of required trials for the meta-analysis have not been reached. Trial Sequential Analysis provides a frequentistic approach to control both type I and type II errors. We define the required information size and the corresponding number of required trials in a meta-analysis and the diversity (D 2 ) measure of heterogeneity. We explain the reasons for using Trial Sequential Analysis of meta-analysis when the actual information size fails to reach the required information size. We present examples drawn from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in systematic reviews with traditional meta-analyses can be reduced using Trial Sequential Analysis. Several empirical studies have demonstrated that the Trial Sequential Analysis provides better control of type I errors and of type II errors than the traditional naïve meta-analysis. Trial Sequential Analysis represents analysis of meta-analytic data, with transparent assumptions, and better control of type I and type II errors than the traditional meta-analysis using naïve unadjusted confidence intervals.

Use of betahistine in the treatment of peripheral vertigo.

PubMed

Ramos Alcocer, Rubén; Ledezma Rodríguez, José Gregorio; Navas Romero, Antonio; Cardenas Nuñez, José Luis; Rodríguez Montoya, Vicente; Deschamps, Jose Junior; Liviac Ticse, Jorge Anibal

2015-01-01

Clinical studies and meta-analyses demonstrated that betahistine is effective and safe in the treatment of Ménière's disease, BPPV (benign paroxysmal positional vertigo), vestibular neuronitis, and other types of peripheral vertigo. The goal of this paper is to review the pharmacological profile of betahistine and the evidence for its effectiveness and safety in the treatment of peripheral vertigo. Selection criteria for the publications on betahistine included randomized clinical trials that evaluated the effectiveness and safety of betahistine vs placebo or active control in the treatment of peripheral vertigo. Recent meta-analyses were also included. Databases searched included PubMed, the Cochrane Ear, Nose and Throat Disorders Group Trials Register, and ICTRP. The review also presents an update on the mechanisms of action, pharmacodynamics, and pharmacokinetics of betahistine. Efficacy and safety of betahistine has been demonstrated in numerous clinical trials. The precise mechanism of action of betahistine is still not completely understood, but the clinical experience demonstrated the benefit of betahistine in different types of peripheral vertigo. In more than 40 years of clinical use, betahistine has shown an excellent safety profile with the usual dose range from 8-48 mg daily. According to clinical studies, betahistine 48 mg daily during 3 months is an effective and safe option for the treatment of peripheral vertigo.

The Benefits of Early Book Sharing (BEBS) for child cognitive and socio-emotional development in South Africa: study protocol for a randomised controlled trial.

PubMed

Dowdall, Nicholas; Cooper, Peter J; Tomlinson, Mark; Skeen, Sarah; Gardner, Frances; Murray, Lynne

2017-03-09

Children in low and middle-income countries (LMICs) are at risk for problems in their cognitive, social and behavioural development. Factors such as a lack of cognitive stimulation, harsh parenting practices, and severe and persistent aggression in early childhood are central to the genesis of these problems. Interventions that target the intersection between early childhood development, parenting, and early violence prevention are required in order to meaningfully address these problems. We are conducting a randomised controlled trial to evaluate a parenting intervention for caregivers of children aged between 23 and 27 months, designed to promote child cognitive and socioemotional development in Khayelitsha, a low-income peri-urban township in South Africa. Families are randomly allocated to a book-sharing intervention group or to a wait-list control group. In the intervention, we train caregivers in supportive book-sharing with young children. Training is carried out in small groups over a period of 8 weeks. Data are collected at baseline, post intervention and at 6 months post intervention. In addition to targeting child cognitive development, the intervention aims to improve child socioemotional functioning. The Benefits of Early Book Sharing (BEBS) trial aims to evaluate the impact of an early parenting intervention on several key risk factors for the development of violence, including aspects of parenting and child cognition, prosocial behaviour, aggression, and socioemotional functioning. The study is being carried out in a LMIC where violence constitutes a major social and health burden. Since the intervention is brief and, with modest levels of training, readily deliverable in LMIC contexts, a demonstration that it is of benefit to both child cognitive and socioemotional development would be of significance. The BEBS trial is registered on the International Standard Randomised Controlled Trial Number database, registration number ISRCTN71109104 . Registered on 9 February 2016. This is version 1 of the protocol for the BEBS trial.

Addressing the management of atrial fibrillation - a systematic review of the role of dronedarone.

PubMed

Podda, Gian Marco; Casazza, Giovanni; Casella, Francesco; Dipaola, Franca; Scannella, Emanuela; Tagliabue, Ludovica

2012-01-01

Atrial fibrillation (AF) is the most common sustained arrhythmia. It occurs in 1%-2% of the general population and its prevalence increases with age. Dronedarone, a noniodinated benzofuran similar to amiodarone, was developed as an antiarrhythmic agent for patients with atrial fibrillation. The aim of our systematic review was to critically evaluate randomized controlled trials that compared treatment with dronedarone versus placebo or amiodarone in patients with atrial fibrillation. Electronic databases (MEDLINE, Embase, and Central) were searched up to November 2011 with no language restrictions. We included randomized controlled trials in which dronedarone was compared to placebo or other drugs in patients with AF. Internal and external validity was assessed. We identified seven papers corresponding to eight randomized controlled trials. The DAFNE, EURIDIS/ADONIS, and ATHENA trials demonstrated a reduction of AF recurrence with dronedarone as compared to placebo in patients with nonpermanent AF. The DIONYSOS study showed that dronedarone is less effective for the prevention of recurrent AF but improved tolerability as compared to amiodarone. Considering patients with permanent AF, the ERATO trial showed that dronedarone had rate-control effects while the PALLAS study was stopped early since stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes were significantly more frequent in subjects treated with dronedarone as compared to placebo. The ANDROMEDA trial included patients with recent hospitalization for heart failure and was terminated early because of excess of deaths in the dronedarone group. Like most antiarrhythmic drugs, dronedarone reduces the recurrence of AF in patients with paroxysmal or persistent AF as compared to placebo. However, relapse rates in the first year of therapy are high. Moreover, dronedarone showed to be less effective than amiodarone. Finally, dronedarone should be avoided in patients with permanent AF and a high risk for cardiovascular events or severe congestive heart failure.

Management of atrial fibrillation in the post-cardiac surgery setting.

PubMed

Daoud, Emile G

2004-02-01

New onset postcardiac surgery AF is a prevalent problem associated with increased morbidity, hospital expense, and length of stay. Those agents that inhibit beta-adrenergic receptors (class II beta-blockers, sotalol, and amiodarone) have been demonstrated to be successful prophylaxis against postoperative AF. Furthermore, those therapies that do not inhibit beta-receptors are not effective prophylactic agents. Until comparative trials demonstrate a significant reduction in postoperative AF without additional adverse effects for sotalol or amiodarone compared with beta-blockers, class II beta-blockers are the preferred prophylactic therapy. If patients are deemed unable to take beta-blockers, amiodarone is likely the best alternative. Although prophylaxis against postoperative AF seems prudent, the impact of prophylactic therapy on length of stay and hospital costs has not been a primary objective of any randomized trial. Furthermore, no studies have compared prophylactic therapy for every patient versus therapy only for those patients who experience AF after heart surgery. In the absence of data from randomized clinical trials, postoperative AF should be managed in a similar fashion to clinical AF with attention to rate control, anticoagulation, and restoration of sinus rhythm.

Adapting Social Neuroscience Measures for Schizophrenia Clinical Trials, Part 2: Trolling the Depths of Psychometric Properties

PubMed Central

Kern, Robert S.

2013-01-01

The psychometric properties of 4 paradigms adapted from the social neuroscience literature were evaluated to determine their suitability for use in clinical trials of schizophrenia. This 2-site study (University of California, Los Angeles and University of North Carolina) included 173 clinically stable schizophrenia outpatients and 88 healthy controls. The social cognition battery was administered twice to the schizophrenia group (baseline, 4-week retest) and once to the control group. The 4 paradigms included 2 that assess perception of nonverbal social and action cues (basic biological motion and emotion in biological motion) and 2 that involve higher level inferences about self and others’ mental states (self-referential memory and empathic accuracy). Each paradigm was evaluated on (1) patient vs healthy control group differences, (2) test-retest reliability, (3) utility as a repeated measure, and (4) tolerability. Of the 4 paradigms, empathic accuracy demonstrated the strongest characteristics, including large between-group differences, adequate test-retest reliability (.72), negligible practice effects, and good tolerability ratings. The other paradigms showed weaker psychometric characteristics in their current forms. These findings highlight challenges in adapting social neuroscience paradigms for use in clinical trials. PMID:24072805

pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure.

PubMed

McNamee, J J; Gillies, M A; Barrett, N A; Agus, A M; Beale, R; Bentley, A; Bodenham, A; Brett, S J; Brodie, D; Finney, S J; Gordon, A J; Griffiths, M; Harrison, D; Jackson, C; McDowell, C; McNally, C; Perkins, G D; Tunnicliffe, W; Vuylsteke, A; Walsh, T S; Wise, M P; Young, D; McAuley, D F

2017-05-01

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO 2 R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO 2 R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO 2 R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO 2 R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

Does Helicobacter pylori infection play a role in iron deficiency anemia? A meta-analysis

PubMed Central

Qu, Xin-Hua; Huang, Xiao-Lu; Xiong, Ping; Zhu, Cui-Ying; Huang, You-Liang; Lu, Lun-Gen; Sun, Xu; Rong, Lan; Zhong, Liang; Sun, Da-Yu; Lin, Hai; Cai, Ming-Ci; Chen, Zhi-Wei; Hu, Bing; Wu, Lian-Ming; Jiang, Yi-Bin; Yan, Wei-Li

2010-01-01

AIM: To perform a meta-analysis of observational studies and randomized controlled trials (RCTs) on the association between Helicobacter pylori (H. pylori) and iron deficiency anemia (IDA). METHODS: A defined search strategy was used to search Medline, Embase, the Cochrane Library, Clinical Trials, Cochrane Central Register of Controlled Trials, Premedline and Healthstar. Odds ratio (OR) was used to evaluate observational epidemiology studies, and weighted mean difference (WMD) was used to demonstrate the difference between control and intervention groups. RESULTS: Fifteen observational studies and 5 RCTs were identified and used for calculation. The pooled OR for observational studies was 2.22 (95% CI: 1.52-3.24, P < 0.0001). The WMD for hemoglobin (HB) was 4.06 g/L (95% CI: -2.57-10.69, P = 0.01), and the WMD for serum ferritin (SF) was 9.47 μg/L (95% CI: -0.50-19.43, P < 0.0001). Results were heterogeneous for all comparisons. CONCLUSION: This meta-analysis on observational studies suggests an association between H. pylori and IDA. In RCTs, eradication of H. pylori can improve HB and SF levels but not significantly. PMID:20143469

Dietary interventions in overweight and obese pregnant women: a systematic review of the content, delivery, and outcomes of randomized controlled trials.

PubMed

Flynn, Angela C; Dalrymple, Kathryn; Barr, Suzanne; Poston, Lucilla; Goff, Louise M; Rogozińska, Ewelina; van Poppel, Mireille N M; Rayanagoudar, Girish; Yeo, SeonAe; Barakat Carballo, Ruben; Perales, Maria; Bogaerts, Annick; Cecatti, Jose G; Dodd, Jodie; Owens, Julie; Devlieger, Roland; Teede, Helena; Haakstad, Lene; Motahari-Tabari, Narges; Tonstad, Serena; Luoto, Riitta; Guelfi, Kym; Petrella, Elisabetta; Phelan, Suzanne; Scudeller, Tânia T; Hauner, Hans; Renault, Kristina; Sagedal, Linda Reme; Stafne, Signe N; Vinter, Christina; Astrup, Arne; Geiker, Nina R W; McAuliffe, Fionnuala M; Mol, Ben W; Thangaratinam, Shakila

2016-05-01

Interventions targeting maternal obesity are a healthcare and public health priority. The objective of this review was to evaluate the adequacy and effectiveness of the methodological designs implemented in dietary intervention trials for obesity in pregnancy. A systematic review of the literature, consistent with PRISMA guidelines, was performed as part of the International Weight Management in Pregnancy collaboration. Thirteen randomized controlled trials, which aimed to modify diet and physical activity in overweight and obese pregnant women, were identified. There was significant variability in the content, delivery, and dietary assessment methods of the dietary interventions examined. A number of studies demonstrated improved dietary behavior in response to diet and/or lifestyle interventions. Nine studies reduced gestational weight gain. This review reveals large methodological variability in dietary interventions to control gestational weight gain and improve clinical outcomes in overweight and obese pregnant women. This lack of consensus limits the ability to develop clinical guidelines and apply the evidence in clinical practice. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial.

PubMed

Mason, Alexina J; Gomes, Manuel; Grieve, Richard; Ulug, Pinar; Powell, Janet T; Carpenter, James

2017-08-01

The analyses of randomised controlled trials with missing data typically assume that, after conditioning on the observed data, the probability of missing data does not depend on the patient's outcome, and so the data are 'missing at random' . This assumption is usually implausible, for example, because patients in relatively poor health may be more likely to drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicited expert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrier to implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop a new practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data. We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN 48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategy versus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation, 21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L). We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinion about quality of life differences between patients with missing versus complete data. We show how this expert opinion can define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing data to depend upon unobserved patient characteristics. A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of life scores were lower on average for the patients with missing versus complete data, but there was considerable uncertainty in these elicited values. The missing at random analysis found that patients randomised to the emergency endovascular strategy versus open repair had higher average (95% credible interval) quality of life scores of 0.062 (-0.005 to 0.130). Our sensitivity analysis that used the elicited expert information as pooled priors found that the gain in average quality of life for the emergency endovascular strategy versus open repair was 0.076 (-0.054 to 0.198). We provide and exemplify a practical tool for eliciting the expert opinion required by recommended approaches to the sensitivity analyses of randomised controlled trials. We show how this approach allows the trial analysis to fully recognise the uncertainty that arises from making alternative, plausible assumptions about the reasons for missing data. This tool can be widely used in the design, analysis and interpretation of future trials, and to facilitate this, materials are available for download.

Internet-based randomised controlled trials for the evaluation of complementary and alternative medicines: probiotics in spondyloarthropathy

PubMed Central

Brophy, Sinead; Burrows, Claire L; Brooks, Caroline; Gravenor, Michael B; Siebert, Stefan; Allen, Stephen J

2008-01-01

Background The clinical effectiveness of complementary and alternative medicines (CAMs) is widely debated because of a lack of clinical trials. The internet may provide an effective and economical approach for undertaking randomised controlled trials (RCTs) of low-risk interventions. We investigated whether the internet could be used to perform an internet-based RCT of a CAM fulfilling the revised CONSORT (Consolidated Standards of Reporting Trials) statement quality checklist for reporting of RCTs. A secondary aim was to examine the effect of probiotics compared to placebo in terms of well-being over 12 weeks. Methods People aged ≥18 years with confirmed spondyloarthropathy living in the United Kingdom with internet access were invited to participate in an internet-based RCT of probiotic compared to placebo for improving well-being and bowel symptoms. The intervention was a probiotic containing 4 strains of live bacteria or identical placebo taken by mouth daily for 3 months. The primary outcome measure was the performance of the trial according to the revised CONSORT statement. Results 147 people were randomised into the trial. The internet-based trial of the CAM fulfilled the revised CONSORT statement such as efficient blinding, allocation concealment, intention to treat analysis and flow of participants through the trial. Recruitment of the required number of participants was completed in 19 months. Sixty-five percent (96/147) completed the entire 3 months of the trial. The trial was low cost and demonstrated that in an intention to treat analysis, probiotics did not improve well-being or bowel symptoms. Conclusion The internet-based RCT proved to be a successful and economical method for examining this CAM intervention. Recruitment, adherence and completion rate were all similar to those reported with conventional RCTs but at a fraction of the cost. Internet-based RCTs can fulfil all the criteria of the revised CONSORT statement and are an appropriate method for studying low-risk interventions. Trial registration ISRCTN36133252 PMID:18190710

“Smart” RCTs: Development of a Smartphone App for Fully Automated Nutrition-Labeling Intervention Trials

PubMed Central

Li, Nicole; Dunford, Elizabeth; Eyles, Helen; Crino, Michelle; Michie, Jo; Ni Mhurchu, Cliona

2016-01-01

Background There is substantial interest in the effects of nutrition labels on consumer food-purchasing behavior. However, conducting randomized controlled trials on the impact of nutrition labels in the real world presents a significant challenge. Objective The Food Label Trial (FLT) smartphone app was developed to enable conducting fully automated trials, delivering intervention remotely, and collecting individual-level data on food purchases for two nutrition-labeling randomized controlled trials (RCTs) in New Zealand and Australia. Methods Two versions of the smartphone app were developed: one for a 5-arm trial (Australian) and the other for a 3-arm trial (New Zealand). The RCT protocols guided requirements for app functionality, that is, obtaining informed consent, two-stage eligibility check, questionnaire administration, randomization, intervention delivery, and outcome assessment. Intervention delivery (nutrition labels) and outcome data collection (individual shopping data) used the smartphone camera technology, where a barcode scanner was used to identify a packaged food and link it with its corresponding match in a food composition database. Scanned products were either recorded in an electronic list (data collection mode) or allocated a nutrition label on screen if matched successfully with an existing product in the database (intervention delivery mode). All recorded data were transmitted to the RCT database hosted on a server. Results In total approximately 4000 users have downloaded the FLT app to date; 606 (Australia) and 1470 (New Zealand) users met the eligibility criteria and were randomized. Individual shopping data collected by participants currently comprise more than 96,000 (Australia) and 229,000 (New Zealand) packaged food and beverage products. Conclusions The FLT app is one of the first smartphone apps to enable conducting fully automated RCTs. Preliminary app usage statistics demonstrate large potential of such technology, both for intervention delivery and data collection. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12614000964617. New Zealand trial: Australian New Zealand Clinical Trials Registry ACTRN12614000644662. PMID:26988128

Periprocedural effects of statins on the incidence of contrast-induced acute kidney injury: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Cheungpasitporn, Wisit; Thongprayoon, Charat; Kittanamongkolchai, Wonngarm; Edmonds, Peter J; O'Corragain, Oisin A; Srivali, Narat; Ungprasert, Patompong; Erickson, Stephen B

2015-05-01

The reports on the efficacy of statins for the prevention of contrast-induced acute kidney injury (CIAKI) remain controversial. The objective of this meta-analysis was to assess the effect of statins for the prevention of CIAKI. Comprehensive literature searches for randomized controlled trials (RCTs) of periprocedural statin treatment for prevention of CIAKI were performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews and clinicaltrials.gov from inception until May 2014. The primary outcome was the incidence of CIAKI. Thirteen prospective RCTs were included in our analysis. Of 5803 patients with contrast exposures, 304 patients (5.2%) had CIAKI. Patients in the statin group had an overall lower incidence of CIAKI (3.6%) compared to the control group (6.9%). Intravenous (IV) fluid hydration was used in both groups of all included studies for prevention of CIAKI. There was a significant protective effect of periprocedural statins on the incidence of CIAKI when compared to the control group [risk ratios (RRs): 0.49; 95% CI: 0.37-0.66, I(2) of 25%]. Our study demonstrates a statistically significant protective effect of statin treatment during procedures with contrast exposures. This finding suggests the use of statins in addition to standard IV crystalloid hydration may be beneficial in the prevention of CIAKI.

A Mechanomodulatory Device to Minimize Incisional Scar Formation

PubMed Central

Wong, Victor W.; Beasley, Bill; Zepeda, John; Dauskardt, Reinhold H.; Yock, Paul G.; Longaker, Michael T.; Gurtner, Geoffrey C.

2013-01-01

Objective To mechanically control the wound environment and prevent cutaneous scar formation. Approach We subjected various material substrates to biomechanical testing to investigate their ability to modulate skin behavior. Combinations of elastomeric materials, adhesives, and strain applicators were evaluated to develop topical stress-shielding devices. Noninvasive imaging modalities were utilized to characterize anatomic site-specific differences in skin biomechanical properties in humans. The devices were tested in a validated large animal model of hypertrophic scarring. Phase I within-patient controlled clinical trials were conducted to confirm their safety and efficacy in scar reduction in patients undergoing abdominoplasty surgery. Results Among the tested materials and device applicators, a polymer device was developed that effectively off-loaded high tension wounds and blocked pro-fibrotic pathways and excess scar formation in red Duroc swine. In humans, different anatomic sites exhibit unique biomechanical properties that may correlate with the propensity to form scars. In the clinical trial, utilization of this device significantly reduced incisional scar formation and improved scar appearance for up to 12 months compared with control incisions that underwent routine postoperative care. Innovation This is the first device that is able to precisely control the mechanical environment of incisional wounds and has been demonstrated in multiple clinical trials to significantly reduce scar formation after surgery. Conclusion Mechanomodulatory strategies to control the incisional wound environment can significantly reduce pathologic scarring and fibrosis after surgery. PMID:24527342

Proactive Control: Neural Oscillatory Correlates of Conflict Anticipation and Response Slowing.

PubMed

Chang, Andrew; Ide, Jaime S; Li, Hsin-Hung; Chen, Chien-Chung; Li, Chiang-Shan R

2017-01-01

Proactive control allows us to anticipate environmental changes and adjust behavioral strategy. In the laboratory, investigators have used a number of different behavioral paradigms, including the stop-signal task (SST), to examine the neural processes of proactive control. Previous functional MRI studies of the SST have demonstrated regional responses to conflict anticipation-the likelihood of a stop signal or P(stop) as estimated by a Bayesian model-and reaction time (RT) slowing and how these responses are interrelated. Here, in an electrophysiological study, we investigated the time-frequency domain substrates of proactive control. The results showed that conflict anticipation as indexed by P(stop) was positively correlated with the power in low-theta band (3-5 Hz) in the fixation (trial onset)-locked interval, and go-RT was negatively correlated with the power in delta-theta band (2-8 Hz) in the go-locked interval. Stimulus prediction error was positively correlated with the power in the low-beta band (12-22 Hz) in the stop-locked interval. Further, the power of the P(stop) and go-RT clusters was negatively correlated, providing a mechanism relating conflict anticipation to RT slowing in the SST. Source reconstruction with beamformer localized these time-frequency activities close to brain regions as revealed by functional MRI in earlier work. These are the novel results to show oscillatory electrophysiological substrates in support of trial-by-trial behavioral adjustment for proactive control.

Effectiveness and cost-effectiveness of a telehealth intervention to support the management of long-term conditions: study protocol for two linked randomized controlled trials.

PubMed

Thomas, Clare L; Man, Mei-See; O'Cathain, Alicia; Hollinghurst, Sandra; Large, Shirley; Edwards, Louisa; Nicholl, Jon; Montgomery, Alan A; Salisbury, Chris

2014-01-24

As the population ages, more people are suffering from long-term health conditions (LTCs). Health services around the world are exploring new ways of supporting people with LTCs and there is great interest in the use of telehealth: technologies such as the Internet, telephone and home self-monitoring. This study aims to evaluate the effectiveness and cost-effectiveness of a telehealth intervention delivered by NHS Direct to support patients with LTCs. Two randomized controlled trials will be conducted in parallel, recruiting patients with two exemplar LTCs: depression or raised cardiovascular disease (CVD) risk. A total of 1,200 patients will be recruited from approximately 42 general practices near Bristol, Sheffield and Southampton, UK. Participants will be randomly allocated to either usual care (control group) or usual care plus the NHS Direct Healthlines Service (intervention group). The intervention is based on a conceptual model incorporating promotion of self-management, optimisation of treatment, coordination of care and engagement of patients and general practitioners. Participants will be provided with tailored help, combining telephone advice from health information advisors with support to use a range of online resources. Participants will access the service for 12 months. Outcomes will be collected at baseline, four, eight and 12 months for the depression trial and baseline, six and 12 months for the CVD risk trial. The primary outcome will be the proportion of patients responding to treatment, defined in the depression trial as a PHQ-9 score <10 and an absolute reduction in PHQ-9 ≥5 after 4 months, and in the CVD risk trial as maintenance or reduction of 10-year CVD risk after 12 months. The study will also assess whether the intervention is cost-effective from the perspective of the NHS and personal social services. An embedded qualitative interview study will explore healthcare professionals' and patients' views of the intervention. This study evaluates a complex telehealth intervention which combines evidence-based components and is delivered by an established healthcare organisation. The study will also analyse health economic information. In doing so, the study hopes to address some of the limitations of previous research by demonstrating the effectiveness and cost-effectiveness of a real world telehealth intervention. Current Controlled Trials: Depression trial ISRCTN14172341 and cardiovascular disease risk trial ISRCTN27508731.

Healthy Beyond Pregnancy, a Web-Based Intervention to Improve Adherence to Postpartum Care: Randomized Controlled Feasibility Trial

PubMed Central

Donovan, Heidi; Wang, Stephanie; Weaver, Carrie; Grove, Jillian Rae; Facco, Francesca Lucia

2017-01-01

Background During the postpartum visit, health care providers address issues with short- and long-term implications for maternal and child health. Women with Medicaid insurance are less likely to return for a postpartum visit compared with women with private insurance. Behavioral economics acknowledges that people do not make exclusively rational choices, rather immediate gratification, cognitive and psychological biases, and social norms influence decision making. Drawing on insights from decision science, behavioral economists have examined how these biases can be modulated through carefully designed interventions. We have developed a Web-based tool, Healthy Beyond Pregnancy, that incorporates empirically derived concepts of behavioral economics to improve adherence rates to the postpartum visit. Objectives The primary objectives of this pilot study were to (1) refine and assess the usability of Healthy Beyond Pregnancy and (2) assess the feasibility of a randomized controlled trial (RCT) of the intervention. Methods We used a multistep process and multidisciplinary team of maternal-fetal medicine physicians, a behavioral economist, and researchers with expertise in behavioral interventions to design Healthy Beyond Pregnancy. We assessed the usability of the program with the Post-Study System Usability Questionnaire (PSSUQ), a validated 7-point scale, and semistructured interviews with postpartum women. We then conducted a feasibility trial to determine the proportion of eligible women who were willing to participate in an RCT of Healthy Beyond Pregnancy and the proportion of women willing to complete the Web-based program. Exploratory outcomes of the pilot trial included attendance at the postpartum visit, uptake of long-acting reversible contraception, and uptake of any contraception. Results The median PSSUQ score for Healthy Beyond Pregnancy was 6.5 (interquartile range: 6.1-7) demonstrating high usability. Semistructured interviews (n=10) provided in-depth comments about users’ experience and further improved the program. A total of 34 postpartum women with Medicaid insurance were approached for the pilot trial, and 30 (88%) were consented and randomized. All women randomized to Healthy Beyond Pregnancy completed the Web-based program, had text-enabled cell phones, and were willing to receive text messages from the study team. Women in the Healthy Beyond Pregnancy arm were more likely to return for a postpartum visit compared with women in the control arm with 85% of women in Healthy Beyond Pregnancy returning versus 53% in the control arm (odds ratio in the Healthy Beyond Pregnancy group: 5.3; 95% CI 0.9-32.0; P=.06). Conclusions We have developed a highly usable and acceptable Web-based program designed to increase attendance at the postpartum visit. Our pilot trial demonstrates that women are willing and able to participate in a randomized trial of a Web-based program and text messaging system. Trial Registration Clinicaltrials.gov NCT03296774; https://clinicaltrials.gov/ct2/show/NCT03296774 (Archived by WebCite at http://www.webcitation.org/6tpgXFzyk) PMID:29017990

Fish Oil Supplementation and Fatty Acid Synthase Expression in the Prostate: A Randomized Controlled Trial. Addendum

DTIC Science & Technology

2011-07-01

controls, Menendez et al demonstrated that addition of omega-3 fatty acids (-3 FA), docosahexanoic acid ( DHA ), alpha- linolenic acid , and -6 FA, γ...AD_________________ Award Number: W81XWH-04-1-0296 TITLE: Fish Oil Supplementation and Fatty Acid ...COVERED 1 March 2010 – 30 June 2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Fish Oil Supplementation and Fatty Acid Synthase Expression in the

Rejecting salient distractors: Generalization from experience.

PubMed

Vatterott, Daniel B; Mozer, Michael C; Vecera, Shaun P

2018-02-01

Distraction impairs performance of many important, everyday tasks. Attentional control limits distraction by preferentially selecting important items for limited-capacity cognitive operations. Research in attentional control has typically investigated the degree to which selection of items is stimulus-driven versus goal-driven. Recent work finds that when observers initially learn a task, the selection is based on stimulus-driven factors, but through experience, goal-driven factors have an increasing influence. The modulation of selection by goals has been studied within the paradigm of learned distractor rejection, in which experience over a sequence of trials enables individuals eventually to ignore a perceptually salient distractor. The experiments presented examine whether observers can generalize learned distractor rejection to novel distractors. Observers searched for a target and ignored a salient color-singleton distractor that appeared in half of the trials. In Experiment 1, observers who learned distractor rejection in a variable environment rejected a novel distractor more effectively than observers who learned distractor rejection in a less variable, homogeneous environment, demonstrating that variable, heterogeneous stimulus environments encourage generalizable learned distractor rejection. Experiments 2 and 3 investigated the time course of learned distractor rejection across the experiment and found that after experiencing four color-singleton distractors in different blocks, observers could effectively reject subsequent novel color-singleton distractors. These results suggest that the optimization of attentional control to the task environment can be interpreted as a form of learning, demonstrating experience's critical role in attentional control.

The vasopressin V(1b) receptor antagonist SSR149415 in the treatment of major depressive and generalized anxiety disorders: results from 4 randomized, double-blind, placebo-controlled studies.

PubMed

Griebel, Guy; Beeské, Sandra; Stahl, Stephen M

2012-11-01

These studies were designed to evaluate the efficacy and tolerability of the first nonpeptide vasopressin V(1b) receptor antagonist, SSR149415, in the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Studies were randomized 8-week, double-blind, placebo-controlled trials evaluating 100- and 250-mg twice daily doses of SSR149415, placebo, and escitalopram 10 mg/day or paroxetine 20 mg/day, conducted from August 2006 through February 2008. Participants met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for MDD or GAD. Baseline Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) total scores were ≥ 24 and 18, respectively, and in the GAD trial baseline Hamilton Anxiety Rating Scale (HARS) score was ≥ 22. Primary efficacy variables included changes from baseline in total score on HDRS or HARS and MADRS, and the secondary variable included changes in the Clinical Global Impressions-Severity of Illness score (CGI-S). A 4-week, double-blind, placebo-controlled study evaluating the effect of 100- and 250-mg twice daily doses of SSR149415 on the hypothalamic-pituitary-adrenal (HPA) axis in MDD patients was also conducted. In the GAD trial, SSR149415 did not separate from placebo on the primary (HARS-100 mg: P = .29; 250 mg: P = .21) and secondary (CGI-S-100 mg: P = .18; 250 mg: P = .24) outcome measures, while paroxetine demonstrated efficacy (HARS: P = .003; CGI-S: P = .01). In 2 MDD trials, SSR149415-treated patients did not show significant improvement from baseline on any outcome measure compared with placebo-treated patients (HDRS-100 mg: P = .21 and .48, respectively; 250 mg: P = .22 and P = .46, respectively; CGI-S-100 mg: P = .64 and P = .82, respectively; 250 mg: P = .33 and P = .08, respectively). In the third MDD study, SSR149415 250 mg (P = .04), but not escitalopram (P = .15), demonstrated significant improvement compared to placebo on the HDRS total score at week 8. SSR149415 had no deleterious effects on the HPA axis. These studies demonstrate that SSR149415 may not be useful for the treatment of GAD and that its antidepressant potential needs to be further evaluated. ClinicalTrials.gov identifiers: NCT00374166 (Sanofi ID number: DFI5880), NCT00361491 (Sanofi ID number: DFI5879), NCT00358631 (Sanofi ID number: DFI5878), NCT01606384 (Sanofi ID number: PDY5467). © Copyright 2012 Physicians Postgraduate Press, Inc.

Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients.

PubMed

Sung, Cynthia; Wei, Yuan; Watanabe, Satoru; Lee, How Sung; Khoo, Yok Moi; Fan, Lu; Rathore, Abhay P S; Chan, Kitti Wing-Ki; Choy, Milly M; Kamaraj, Uma S; Sessions, October M; Aw, Pauline; de Sessions, Paola F; Lee, Bernett; Connolly, John E; Hibberd, Martin L; Vijaykrishna, Dhanasekaran; Wijaya, Limin; Ooi, Eng Eong; Low, Jenny Guek-Hong; Vasudevan, Subhash G

2016-08-01

CELADEN was a randomized placebo-controlled trial of 50 patients with confirmed dengue fever to evaluate the efficacy and safety of celgosivir (A study registered at ClinicalTrials.gov, number NCT01619969). Celgosivir was given as a 400 mg loading dose and 200 mg bid (twice a day) over 5 days. Replication competent virus was measured by plaque assay and compared to reverse transcription quantitative PCR (qPCR) of viral RNA. Pharmacokinetics (PK) correlations with viremia, immunological profiling, next generation sequence (NGS) analysis and hematological data were evaluated as exploratory endpoints here to identify possible signals of pharmacological activity. Viremia by plaque assay strongly correlated with qPCR during the first four days. Immunological profiling demonstrated a qualitative shift in T helper cell profile during the course of infection. NGS analysis did not reveal any prominent signature that could be associated with drug treatment; however the phylogenetic spread of patients' isolates underlines the importance of strain variability that may potentially confound interpretation of dengue drug trials conducted during different outbreaks and in different countries. Celgosivir rapidly converted to castanospermine (Cast) with mean peak and trough concentrations of 5727 ng/mL (30.2 μM) and 430 ng/mL (2.3 μM), respectively and cleared with a half-life of 2.5 (± 0.6) hr. Mean viral log reduction between day 2 and 4 (VLR2-4) was significantly greater in secondary dengue than primary dengue (p = 0.002). VLR2-4 did not correlate with drug AUC but showed a trend of greater response with increasing Cmin. PK modeling identified dosing regimens predicted to achieve 2.4 to 4.5 times higher Cmin. than in the CELADEN trial for only 13% to 33% increase in overall dose. A small, non-statistical trend towards better outcome on platelet nadir and difference between maximum and minimum hematocrit was observed in celgosivir-treated patients with secondary dengue infection. Optimization of the dosing regimen and patient stratification may enhance the ability of a clinical trial to demonstrate celgosivir activity in treating dengue fever based on hematological endpoints. A new clinical trial with a revised dosing regimen is slated to start in 2016 (NCT02569827). Furthermore celgosivir's potential value for treatment of other flaviruses such as Zika virus should be investigated urgently. ClinicalTrials.gov NCT01619969.

Determining the impact of a new physiotherapist-led primary care model for back pain: protocol for a pilot cluster randomized controlled trial.

PubMed

Miller, Jordan; Barber, David; Donnelly, Catherine; French, Simon; Green, Michael; Hill, Jonathan; MacDermid, Joy; Marsh, Jacquelyn; Norman, Kathleen; Richardson, Julie; Taljaard, Monica; Wideman, Timothy; Cooper, Lynn; McPhee, Colleen

2017-11-09

Back pain is a leading contributor to disability, healthcare costs, and lost work. Family physicians are the most common first point of contact in the healthcare system for people with back pain, but physiotherapists (PTs) may be able to support the primary care team through evidence-based primary care. A cluster randomized trial is needed to determine the clinical, health system, and societal impact of a primary care model that integrates physiotherapists at the first visit for people with back pain. Prior to conducting a future fully powered cluster randomized trial, we need to demonstrate feasibility of the methods. Therefore, the purpose of this pilot study will be to: 1) Determine feasibility of patient recruitment, assessment procedures, and retention. 2) Determine the feasibility of training and implementation of a new PT-led primary care model for low back pain (LBP) 3) Explore the perspectives of patients and healthcare providers (HCPs) related to their experiences and attitudes towards the new service delivery model, barriers/facilitators to implementation, perceived satisfaction, perceived value, and impact on clinic processes and patient outcomes. This pilot cluster randomized controlled trial will enroll four sites and randomize them to implement a new PT-led primary care model for back pain or a usual physician-led primary care model. All adults booking a primary care visit for back pain will be invited to participate. Feasibility outcomes will include: recruitment and retention rates, completeness of assessment data, PT training participation and confidence after training, and PT treatment fidelity. Secondary outcomes will include the clinical, health system, cost, and process outcomes planned for the future fully powered cluster trial. Results will be analyzed and reported descriptively and qualitatively. To explore perspectives of both HCPs and patients, we will conduct semi-structured qualitative interviews with patients and focus groups with HCPs from participants in the PT-led primary care sites. If this pilot demonstrates feasibility, a fully powered trial will provide evidence that has the potential to transform primary care for back pain. The full trial will inform future service design, whether these models should be more widely implemented, and training agendas. ClinicalTrials.gov, NCT03320148 . Submitted for registration on 17 September 2017.

Economic evaluation of factorial randomised controlled trials: challenges, methods and recommendations

PubMed Central

Gray, Alastair

2017-01-01

Increasing numbers of economic evaluations are conducted alongside randomised controlled trials. Such studies include factorial trials, which randomise patients to different levels of two or more factors and can therefore evaluate the effect of multiple treatments alone and in combination. Factorial trials can provide increased statistical power or assess interactions between treatments, but raise additional challenges for trial‐based economic evaluations: interactions may occur more commonly for costs and quality‐adjusted life‐years (QALYs) than for clinical endpoints; economic endpoints raise challenges for transformation and regression analysis; and both factors must be considered simultaneously to assess which treatment combination represents best value for money. This article aims to examine issues associated with factorial trials that include assessment of costs and/or cost‐effectiveness, describe the methods that can be used to analyse such studies and make recommendations for health economists, statisticians and trialists. A hypothetical worked example is used to illustrate the challenges and demonstrate ways in which economic evaluations of factorial trials may be conducted, and how these methods affect the results and conclusions. Ignoring interactions introduces bias that could result in adopting a treatment that does not make best use of healthcare resources, while considering all interactions avoids bias but reduces statistical power. We also introduce the concept of the opportunity cost of ignoring interactions as a measure of the bias introduced by not taking account of all interactions. We conclude by offering recommendations for planning, analysing and reporting economic evaluations based on factorial trials, taking increased analysis costs into account. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:28470760

Vaccine approaches to malaria control and elimination: Insights from mathematical models.

PubMed

White, Michael T; Verity, Robert; Churcher, Thomas S; Ghani, Azra C

2015-12-22

A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts. Several candidate vaccines targeting different stages of the malaria parasite's lifecycle are currently under development, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection, having recently completed Phase III trials. Predicting the public health impact of a candidate malaria vaccine requires using clinical trial data to estimate the vaccine's efficacy profile--the initial efficacy following vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacy profile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematical models. Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocytic vaccines and transmission-blocking vaccines from clinical trial data. In the case of RTS,S/AS01, model estimates from Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection, with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waning over the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II or Phase III clinical trials so we review ongoing work investigating how a clinical trial might be designed to ensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstrate how parameters estimated from clinical trials can be used to predict the impact of vaccination campaigns on malaria using a mathematical model of malaria transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Clinical trials of laparoscopic gastric cancer surgery in South Korea: review and prospect].

PubMed

Zhu, Chunchao; Zhao, Gang; Cao, Hui

2018-02-25

Laparoscopic technology is gradually accepted in gastric cancer surgery, whose efficacy has been demonstrated by some clinical researches. Randomized controlled trials (RCT) are considered as the most important evidence to prove clinical outcomes of laparoscopic surgery for gastric cancer. Korean gastric surgeons have made great contributions to RCT in laparoscopic gastric cancer surgery. KLASS (Korean Laparoscopic Gastrointestinal Surgery Study Group) is one of the most important forerunner and global leader of clinical trials of gastric cancer treatment. KLASS series clinical trials are attracting global attention because of the significant value of surgical treatment for gastric cancer. The RCTs in Korea involve in many aspects of laparoscopic gastrectomy for gastric cancer, including laparoscopy application in early gastric cancer (KLASS-01, KLASS-03 and KLASS-07), advanced gastric cancer (KLASS-02 and KLASS-06), function-preserving gastrectomy (KLASS-04,KLASS-05) and sentinel node navigation surgery (SENORITA trial). In order to share some informations of these RCTs, we review and prospect some important clinical trials of laparoscopic gastric cancer surgery in Korea. With the experience of Korean gastric surgeons, we can make more progress in our own clinical trials of laparoscopic gastric cancer surgery.

Clinical trials update from the Heart Failure Society of America Meeting 2009: FAST, IMPROVE-HF, COACH galectin-3 substudy, HF-ACTION nuclear substudy, DAD-HF, and MARVEL-1.

PubMed

Lainscak, Mitja; Coletta, Alison P; Sherwi, Nasser; Cleland, John G F

2010-02-01

This article presents findings and a commentary on late-breaking trials presented during the meeting of the Heart Failure Society of America in September 2009. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The FAST trial showed somewhat better performance of intrathoracic impedance for prediction of deterioration in patients with heart failure (HF) when compared with daily weighing. The IMPROVE-HF study reported the benefits of education on the management of patients with systolic HF. Galectin-3 appeared a useful method for improving risk stratification of patients with chronic HF in a substudy of the COACH trial. A nuclear substudy of the HF-ACTION trial failed to demonstrate that resting myocardial perfusion imaging, a measure of myocardial scar and viability, was clinically useful. A small randomized controlled trial (DAD-HF) suggested that the use of low-dose dopamine in patients with acutely decompensated HF was associated with less deterioration in renal function and less hypokalaemia. The MARVEL-1 trial raises further concerns about the safety of myoblast transplantation in ischaemic HF.

Strategies for informed sample size reduction in adaptive controlled clinical trials

NASA Astrophysics Data System (ADS)

Arandjelović, Ognjen

2017-12-01

Clinical trial adaptation refers to any adjustment of the trial protocol after the onset of the trial. The main goal is to make the process of introducing new medical interventions to patients more efficient. The principal challenge, which is an outstanding research problem, is to be found in the question of how adaptation should be performed so as to minimize the chance of distorting the outcome of the trial. In this paper, we propose a novel method for achieving this. Unlike most of the previously published work, our approach focuses on trial adaptation by sample size adjustment, i.e. by reducing the number of trial participants in a statistically informed manner. Our key idea is to select the sample subset for removal in a manner which minimizes the associated loss of information. We formalize this notion and describe three algorithms which approach the problem in different ways, respectively, using (i) repeated random draws, (ii) a genetic algorithm, and (iii) what we term pair-wise sample compatibilities. Experiments on simulated data demonstrate the effectiveness of all three approaches, with a consistently superior performance exhibited by the pair-wise sample compatibilities-based method.

Cannabis and schizophrenia.

PubMed

Pushpa-Rajah, Jonathan A; McLoughlin, Benjamin C; Gillies, Donna; Rathbone, John; Variend, Hannele; Kalakouti, Eliana; Kyprianou, Katerina

2015-03-01

Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake. To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia. To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia. To assess the effects of cannabinoids (cannabis-related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia. We searched the Cochrane Schizophrenia Group Trials Register (August 2013) and all references of articles selected for further relevant trials. We contacted the first author of included studies for unpublished trials or data. We included all randomized controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed: (1) treatments to reduce cannabis use in people with schizophrenia and (2) the effects of cannabinoids on people with schizophrenia. Results are limited and inconclusive due to the small number and size of randomized controlled trials available and quality of data reporting within these trials. Currently, there is no evidence to demonstrate that one type of adjunct psychological therapy or one type of drug therapy is more effective than another. There is also insufficient evidence to show that cannabidiol has an antipsychotic effect. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Olmesartan/amlodipine: a review of its use in the management of hypertension

PubMed Central

Kreutz, R

2011-01-01

Combination therapy is an effective strategy to increase antihypertensive efficacy in those patients with poor blood pressure (BP) control. In order to achieve BP targets, at least 75% of patients may require combination therapy, and European guidelines advocate this approach, particularly in those patients with a high cardiovascular risk. Evidence from large, randomized controlled trials, and the European hypertension treatment guidelines is supportive of the use of an angiotensin receptor blocker (ARB) with a calcium channel blocker (CCB). Fixed-dose combination formulations of olmesartan medoxomil, an ARB, and the CCB amlodipine are approved in several European countries for patients with essential hypertension. The olmesartan/amlodipine combination has demonstrated greater efficacy than its component monotherapies in reducing BP in patients with mild-to-severe hypertension. Significantly greater reductions in seated diastolic BP were observed between baseline and after eight weeks of treatment with olmesartan/amlodipine, compared with equivalent doses of olmesartan or amolodipine monotherapy (P < 0.001), in the factorial Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial. About 85% of the maximal BP reductions after the 8-week treatment period were already observed after two weeks. Uptitration as necessary, with or without hydrochlorothiazide, allowed the majority of patients to achieve BP control in a 44-week open-label extension treatment period to the COACH trial. The use of olmesartan/amlodipine allowed up to 54% of patients, with previously inadequate responses to amlodipine or olmesartan monotherapy, to achieve their BP goals. Data from post-registration studies using tight BP control and forced titration regimens have further demonstrated the high efficacy of olmesartan/amlodipine in achieving BP goal rates. Moreover, consistent reductions in BP were observed over the 24-hour dosing interval using ambulatory measurements. Olmesartan/amlodipine was generally well tolerated over the short- and long-term, with a lower frequency of peripheral edema with olmesartan/amlodipine 40/10 mg than with amlodipine 10 mg monotherapy. PMID:21490944

Lithium as an adjunct to radioactive iodine for the treatment of hyperthyroidism: a systematic review and meta-analysis.

PubMed

Kessler, Lynn; Palla, Jyothsna; Baru, Joshua S; Onyenwenyi, Chioma; George, Amrutha M; Lucas, Brian P

2014-07-01

Radioactive iodine (RAI) is commonly used in the treatment of hyperthyroidism but is not uniformly successful. Lithium increases thyroidal iodine retention without reducing iodide uptake, increasing the radiation dose to the thyroid when administered with RAI. Although these actions suggest that adjuvant lithium may increase the efficacy of RAI, its role as an adjunct to RAI remains contentious. To evaluate the safety and efficacy of adding lithium to RAI to treat hyperthyroidism. Relevant studies were identified by a search of Medline and the Cochrane Central Register of Controlled Trials. To be included, a study had to be a controlled trial comparing the effect of RAI alone to RAI with lithium in the treatment of hyperthyroidism. Relevant data were extracted and meta-analyses were performed. Of the 75 identified studies, 6 met the inclusion criteria; 4 of these studies were interventional and 2 were observational trials. Meta-analysis of the observational trials (N = 851), both of which were retrospective cohort studies, showed significant improvement in the primary outcome (i.e., cure rate) with adjunctive lithium (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.24 to 2.96). The combined interventional trials (N = 485) also showed an improvement in cure rate, but the difference did not reach statistical significance (OR, 1.28; 95% CI, 0.85 to 1.91). Adjunctive lithium reduced time to cure and blunted thyroid hormone excursions after RAI. Lithium-related side effects were infrequent and usually mild. The observational trials demonstrated significant improvement in the cure rate of hyperthyroidism when lithium is added to RAI. The improvements shown in the interventional trials did not reach statistical significance due to the effect of a single, large negative trial.

Efficacy of leukocyte- and platelet-rich fibrin in wound healing: a randomized controlled clinical trial.

PubMed

Chignon-Sicard, Bérengère; Georgiou, Charalambos A; Fontas, Eric; David, Sylvain; Dumas, Pierre; Ihrai, Tarik; Lebreton, Elisabeth

2012-12-01

Application of platelet concentrates to wounds could speed healing. Leukocyte- and platelet-rich fibrin, a relatively recent development, stands out from the other preparations. This prospective, randomized, controlled clinical trial studied the rate of healing of postoperative hand wounds after a single application of leukocyte- and platelet-rich fibrin. Eligible patients were healthy individuals older than 18 years who had been scheduled for elective McCash (open palm) surgery for Dupuytren disease at the Plastic and Hand Surgery Department of Nice's University Hospital between August of 2007 and February of 2010. The control group received the reference care of petroleum jelly mesh (Vaselitulle), and test patients had leukocyte- and platelet-rich fibrin applied. The primary endpoint was healing delay measured in postoperative days. Secondary endpoints included pain, bleeding, and wound exudate. The trial was carried out as a single-blind trial. Among the 68 randomized patients, 33 patients in the leukocyte- and platelet-rich fibrin group and 31 in the Vaselitulle group were analyzed. Primary endpoint analysis showed a median healing delay of 24 days (interquartile range, 18 to 28 days) for the fibrin group and 29 days (interquartile range, 26 to 35 days) for the Vaselitulle group (p = 0.014, log-rank test). Postoperative pain assessment, bleeding, and exudate were always lower for the fibrin group, but not significantly so. The authors trial demonstrates that a single leukocyte- and platelet-rich fibrin application on fresh postoperative hand wounds shows a median improvement of 5 days in comparison with the standard treatment. Therapeutic, II.

Rationale and design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND).

PubMed

Hedayati, S Susan; Daniel, Divya M; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H; Unruh, Mark; Weisbord, Steven; Young, Bessie A; Mehrotra, Rajnish

2016-03-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. Published by Elsevier Inc.

Rationale and Design of A Trial of Sertraline vs. Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression (ASCEND)

PubMed Central

Hedayati, S. Susan; Daniel, Divya M.; Cohen, Scott; Comstock, Bryan; Cukor, Daniel; Diaz-Linhart, Yaminette; Dember, Laura M.; Dubovsky, Amelia; Greene, Tom; Grote, Nancy; Heagerty, Patrick; Katon, Wayne; Kimmel, Paul L.; Kutner, Nancy; Linke, Lori; Quinn, Davin; Rue, Tessa; Trivedi, Madhukar H.; Unruh, Mark; Weisbord, Steven; Young, Bessie A.; Mehrotra, Rajnish

2015-01-01

Major Depressive Disorder (MDD) is highly prevalent in patients with End Stage Renal Disease (ESRD) treated with maintenance hemodialysis (HD). Despite the high prevalence and robust data demonstrating an independent association between depression and poor clinical and patient-reported outcomes, MDD is under-treated when identified in such patients. This may in part be due to the paucity of evidence confirming the safety and efficacy of treatments for depression in this population. It is also unclear whether HD patients are interested in receiving treatment for depression. ASCEND (Clinical Trials Identifier Number NCT02358343), A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT) for End-stage Renal Disease Patients with Depression, was designed as a multi-center, 12-week, open-label, randomized, controlled trial of prevalent HD patients with comorbid MDD or dysthymia. It will compare (1) a single Engagement Interview vs. a control visit for the probability of initiating treatment for comorbid depression in up to 400 patients; and (2) individual chair-side CBT vs. flexible-dose treatment with a selective serotonin reuptake inhibitor, sertraline, for improvement of depressive symptoms in 180 of the up to 400 patients. The evolution of depressive symptoms will also be examined in a prospective longitudinal cohort of 90 HD patients who choose not to be treated for depression. We discuss the rationale and design of ASCEND, the first large-scale randomized controlled trial evaluating efficacy of non-pharmacologic vs. pharmacologic treatment of depression in HD patients for patient-centered outcomes. PMID:26621218

Some Recent Developments on Financial Incentives for Smoking Cessation Among Pregnant and Newly Postpartum Women.

PubMed

Higgins, Stephen T; Solomon, Laura J

2016-03-01

Smoking during pregnancy is a leading preventable cause of poor pregnancy outcomes and immediate and longer-term adverse health outcomes among exposed offspring. Developing more effective smoking-cessation interventions for pregnant women has been a public-health priority for more than thirty years. We review developments over the past three years (2012-15) on the use of financial incentives to promote smoking cessation among pregnant women. We searched the literature for reports on primary and secondary analyses and reviews of controlled trials on this topic published in peer-reviewed journals using the search engine PubMed, reviewed bibliographies of published articles, and consulted expert colleagues. The search revealed several important developments, with the following three being especially noteworthy. First, the review identified four new randomized controlled trials, three of which further supported the efficacy of this treatment approach. One of the three trials supporting efficacy also included the first econometric analysis of this treatment approach showing financial incentives with pregnant smokers to be highly cost-effective. Second, two Cochrane reviews were published during this 3-year period covering the more recent and earlier efficacy trials. Meta-analyses in both reviews supported the efficacy of the approach. Lastly, the first effectiveness trial was reported demonstrating that financial incentives increased abstinence rates above control levels when implemented by obstetrical clinic staff in a large urban hospital working with community tobacco interventionists. Overall, t here is a growing and compelling body of evidence supporting the efficacy and cost-effectiveness of financial incentives for smoking cessation among pregnant women.

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

PubMed

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

2017-09-26

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

Preoperative education interventions to reduce anxiety and improve recovery among cardiac surgery patients: a review of randomised controlled trials.

PubMed

Guo, Ping

2015-01-01

To update evidence of the effectiveness of preoperative education among cardiac surgery patients. Patients awaiting cardiac surgery may experience high levels of anxiety and depression, which can adversely affect their existing disease and surgery and result in prolonged recovery. There is evidence that preoperative education interventions can lead to improved patient experiences and positive postoperative outcomes among a mix of general surgical patients. However, a previous review suggested limited evidence to support the positive impact of preoperative education on patients' recovery from cardiac surgery. Comprehensive review of the literature. The Cochrane Central Register of Controlled Trials from the Cochrane Library, MEDLINE, CINAHL, PsycINFO, EMBASE and Web of Science were searched for English-language articles published between 2000-2011. Original articles were included reporting randomised controlled trials of cardiac preoperative education interventions. Six trials were identified and have produced conflicting findings. Some trials have demonstrated the effects of preoperative education on improving physical and psychosocial recovery of cardiac patients, while others found no evidence that patients' anxiety is reduced or of any effect on pain or hospital stay. Evidence of the effectiveness of preoperative education interventions among cardiac surgery patients remains inconclusive. Further research is needed to evaluate cardiac preoperative education interventions for sustained effect and in non-Western countries. A nurse-coordinated multidisciplinary preoperative education approach may offer a way forward to provide a more effective and efficient service. Staff training in developing and delivering such interventions is a priority. © 2014 John Wiley & Sons Ltd.

Renal Denervation for Treatment of Hypertension: a Second Start and New Challenges.

PubMed

Persu, Alexandre; Kjeldsen, Sverre; Staessen, Jan A; Azizi, Michel

2016-01-01

Following the publication of the randomized controlled but open-label trial Symplicity HTN-2, catheter-based renal sympathetic denervation was proposed as a novel treatment for drug-resistant hypertension. Thousands of procedures were routinely performed in Europe, Australia and Asia, and many observational studies were published. A sudden shift from overoptimistic views to radical scepticism occurred later, when the large US randomized sham-controlled trial Symplicity HTN-3 failed to meet its primary blood pressure lowering efficacy endpoint. Experts are divided on the reasons accounting for the large discrepancy between the results of initial studies and those of Symplicity HTN-3. Indeed, the blood pressure lowering effect associated with renal denervation was overestimated in initial trials due to various patient and physician-related biases, whereas it could have been underestimated in Symplicity HTN-3, which was well designed but not rigorously executed. Still, there is a large consensus on the need to further study catheter-based renal denervation in more controlled conditions, with particular emphasis on identification of predictors of blood pressure response. US and European experts have recently issued very similar recommendations on design of upcoming trials, procedural aspects, drug treatment, patient population and inclusion-exclusion criteria. Application of these new standards may represent a second chance for renal denervation to demonstrate--or not--its efficacy and safety in various patient populations. With its highly standardized treatment regimen, the French trial DENERHTN paved the way for this new approach and may inspire upcoming studies testing novel renal denervation systems in different populations.

Critical Analysis of the Efficacy of Meditation Therapies for Acute and Subacute Phase Treatment of Depressive Disorders: A Systematic Review

PubMed Central

Jain, Felipe A.; Walsh, Roger N.; Eisendrath, Stuart J.; Christensen, Scott; Cahn, B. Rael

2014-01-01

Background Recently, the application of meditative practices to the treatment of depressive disorders has met with increasing clinical and scientific interest, due to a lower side-effect burden, potential reduction of polypharmacy, as well as theoretical considerations that such interventions may target some of the cognitive roots of depression. We aimed to determine the state of the evidence supporting this application. Methods Randomized, controlled trials of techniques meeting the Agency for Healthcare Research and Quality (AHRQ) definition of meditation, for participants suffering from clinically diagnosed depressive disorders, not currently in remission, were selected. Meditation therapies were separated into praxis (i.e. how they were applied) components, and trial outcomes were reviewed. Results Eighteen studies meeting inclusionary criteria were identified, encompassing seven distinct techniques and 1173 patients, with Mindfulness-Based Cognitive Therapy comprising the largest proportion. Studies including patients suffering from acute major depressive episodes (N = 10 studies), and those with residual subacute clinical symptoms despite initial treatment (N = 8), demonstrated moderate to large reductions in depression symptoms within group, and relative to control groups. There was significant heterogeneity of techniques and trial designs. Conclusions A substantial body of evidence indicates that meditation therapies may have salutary effects on patients suffering from clinical depressive disorders during the acute and subacute phases of treatment. Due to methodological deficiences and trial heterogeneity, large-scale, randomized controlled trials with well-described comparator interventions and measures of expectation are needed to clarify the role of meditation in the depression treatment armamentarium. PMID:25591492

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

PubMed Central

Volkmar, Fred R.; Bloch, Michael H.

2012-01-01

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

Variable Cadence Walking and Ground Adaptive Standing with a Powered Ankle Prosthesis

PubMed Central

Shultz, Amanda H.; Lawson, Brian E.; Goldfarb, Michael

2015-01-01

Abstract This paper describes a control approach that provides walking and standing functionality for a powered ankle prosthesis, and demonstrates the efficacy of the approach in experiments in which a unilateral transtibial amputee subject walks with the prosthesis at variable cadences, and stands on various slopes. Both controllers incorporate a finite-state structure that emulates healthy ankle joint behavior via a series of piecewise passive impedance functions. The walking controller incorporates an algorithm to modify impedance parameters based on estimated cadence, while the standing controller incorporates an algorithm to modulate the ankle equilibrium angle in order to adapt to the ground slope and user posture, and the supervisory controller selects between the walking and standing controllers. The system is shown to reproduce several essential biomechanical features of the healthy joint during walking, particularly relative to a passive prosthesis, and is shown to adapt to variable cadences. The system is also shown to adapt to slopes over a range of ± 15 deg and to provide support to the user in a manner that is biomimetic, as validated by quasi-static stiffness measurements recorded by the prosthesis. Data from standing trials indicate that the user places more weight on the powered prosthesis than on his passive prosthesis when standing on sloped surfaces, particularly at angles of 10 deg or greater. The authors also demonstrated that the prosthesis typically began providing support within 1 s of initial contact with the ground. Further, the supervisory controller was shown to be effective in switching between walking and standing, as well as in determining ground slope just prior to the transition from the standing controller to the walking controller, where the estimated ground slope was within 1.25 deg of the actual ground slope for all trials. PMID:25955789

Attention and interpretation bias modification treatment for social anxiety disorder: A randomized clinical trial of efficacy and synergy.

PubMed

Naim, Reut; Kivity, Yogev; Bar-Haim, Yair; Huppert, Jonathan D

2018-06-01

Attention bias modification treatment (ABMT) and cognitive bias modification of interpretation (CBM-I) both have demonstrated efficacy in alleviating social anxiety, but how they compare with each other, their combination, and with a combined control condition has not been studied. We examined their relative and combined efficacy compared to control conditions in a randomized controlled trial (RCT). Ninety-five adults diagnosed with social anxiety disorder (SAD), were randomly allocated to 4 groups: ABMT + CBM-I control (hereafter ABMT; n = 23), CBM-I + ABMT control (hereafter CBM-I; n = 24), combined ABMT + CBM-I (n = 23), and combined control (n = 25). Treatment included eight sessions over four weeks. Clinician-rated and self-reported measures of social anxiety symptoms, functional impairment, and threat-related attention and interpretive biases were evaluated at baseline, post-treatment, and 3-month follow-up. ABMT yielded greater symptom reduction as measured by both clinician-ratings (Cohen's ds = 0.57-0.70) and self-reports (ds = 0.70-0.85) compared with the CBM-I, the combined ABMT + CBM-I, and the combined control conditions. Neither of the other conditions demonstrated superior symptom change compared to the control condition. No group differences were found for functioning or cognitive biases measures. Limitations mainly include the mix of active and control treatments applied across the different groups. Therefore, the net effect of each of the treatments by itself could not be clearly tested. Results suggest superiority of ABMT compared to CBM-I and their combination in terms of symptom reduction. Possible interpretations and methodological issues underlying the observed findings are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

PubMed

Vilain, Katherine R; Magnuson, Elizabeth A; Li, Haiyan; Clark, Wayne M; Begg, Richard J; Sam, Albert D; Sternbergh, W Charles; Weaver, Fred A; Gray, William A; Voeks, Jenifer H; Brott, Thomas G; Cohen, David J

2012-09-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, -$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00004732.

CAMERA2 - combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection: study protocol for a randomised controlled trial.

PubMed

Tong, Steven Y C; Nelson, Jane; Paterson, David L; Fowler, Vance G; Howden, Benjamin P; Cheng, Allen C; Chatfield, Mark; Lipman, Jeffrey; Van Hal, Sebastian; O'Sullivan, Matthew; Robinson, James O; Yahav, Dafna; Lye, David; Davis, Joshua S

2016-03-31

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a serious infection resulting in 20-50 % 90-day mortality. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. Surprisingly, there has been consistent in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or daptomycin and an anti-staphylococcal β-lactam antibiotic. There is also growing clinical data to support such combinations, including a recent pilot randomised controlled trial (RCT) that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone. Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia. We will perform an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older) with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion. Participants will be randomised to vancomycin or daptomycin (standard therapy) given intravenously or to standard therapy plus 7 days of an anti-staphylococcal β-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4) microbiological treatment failure. The recruitment target of 440 patients is based on an expected failure rate for the primary outcome of 30 % in the control arm and the ability to detect a clinically meaningful absolute decrease of 12.5 %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients will not be evaluable for the primary endpoint. Key potential advantages of adding anti-staphylococcal β-lactams to standard therapy for MRSA bacteraemia include their safety profile, low cost, and wide availability. ClinicalTrials.gov Identifier: NCT02365493 . Registered 24 February 2015.

Ear Acupuncture Therapy for Masticatory Myofascial and Temporomandibular Pain: A Controlled Clinical Trial.

PubMed

Ferreira, Luciano Ambrosio; Grossmann, Eduardo; Januzzi, Eduardo; Gonçalves, Rafael Tardin Rosa Ferraz; Mares, Fernando Antonio Guedes; de Paula, Marcos Vinicius Queiroz; Carvalho, Antonio Carlos Pires

2015-01-01

Ear acupuncture works by reducing painful sensations with analgesic effect through microsystem therapy and has been demonstrated to be as effective as conventional therapies in the control of facial pain. This clinical trial aimed to evaluate the adjuvant action of auricular acupuncture through an observation of the evolution of temporomandibular and masticatory myofascial symptoms in two groups defined by the therapies elected: auricular acupuncture associated with occlusal splint (study) and the use of the occlusal splint plate alone (control). We have selected 20 patients, who were randomly allocated into two groups of ten individuals. Symptoms were evaluated in five different moments, every seven days. We analyzed the orofacial muscle and joint palpation in order to measure the intensity of the experienced pain. Both groups showed a statistically significant decrease in muscle and joint symptoms (p < 0.05). However, comparisons between the groups showed an expressive and significant reduction of symptomatology in the study group (p < 0.05) already on the first week of therapy. According to the results, to the methodological criteria developed and statistical analysis applied, the conclusion is that auricular acupuncture therapy has synergistic action on conventional occlusal splint treatment. It was demonstrated to be effective in the reduction of symptoms in the short term.

Multi-compartment medication devices and patient compliance.

PubMed

McGraw, Caroline

2004-07-01

Multi-compartment medication compliance devices are widely used in primary care. The aim of this review is to reveal whether they are effective in promoting adherence among non-adherent adults living at home. Searches were undertaken using two electronic databases (Medline (1966-2003) and International Pharmaceutical Abstracts (1970-2002)). Only randomized controlled trials (including crossover studies) were included in the review. Participants had to be non-institutionalized adults receiving one or more prescription medicines each day and displaying problems with adherence. Studies had to compare multi-compartment medication compliance devices to standard packaging and outcome measures and to include either pill counts, biological assays and/or clinical response. Articles were selected if they described a follow up period of at least three months and demonstrated that over 80% of participants had completed the trial. Two studies were identified that met the criteria, reporting data on a total of 148 patients. The findings from the first study found diabetic patients receiving medication in a compliance device demonstrated better glucose control than patients receiving medication in standard packaging. The second study found compliance devices had no impact on blood pressure control in hypertensive patients. Further research needs to be conducted to assess the effectiveness of multi-compartment medication compliance devices in promoting adherence among non-adherent adults living at home.

A Randomised Controlled Single-Blind Trial of the Efficacy of Reiki at Benefitting Mood and Well-Being

PubMed Central

Bowden, Deborah; Goddard, Lorna; Gruzelier, John

2011-01-01

This is a constructive replication of a previous trial conducted by Bowden et al. (2010), where students who had received Reiki demonstrated greater health and mood benefits than those who received no Reiki. The current study examined impact on anxiety/depression. 40 university students—half with high depression and/or anxiety and half with low depression and/or anxiety—were randomly assigned to receive Reiki or to a non-Reiki control group. Participants experienced six 30-minute sessions over a period of two to eight weeks, where they were blind to whether noncontact Reiki was administered as their attention was absorbed in a guided relaxation. The efficacy of the intervention was assessed pre-post intervention and at five-week follow-up by self-report measures of mood, illness symptoms, and sleep. The participants with high anxiety and/or depression who received Reiki showed a progressive improvement in overall mood, which was significantly better at five-week follow-up, while no change was seen in the controls. While the Reiki group did not demonstrate the comparatively greater reduction in symptoms of illness seen in our earlier study, the findings of both studies suggest that Reiki may benefit mood. PMID:21584234

Ear Acupuncture Therapy for Masticatory Myofascial and Temporomandibular Pain: A Controlled Clinical Trial

PubMed Central

Ferreira, Luciano Ambrosio; Grossmann, Eduardo; Januzzi, Eduardo; Gonçalves, Rafael Tardin Rosa Ferraz; Mares, Fernando Antonio Guedes; de Paula, Marcos Vinicius Queiroz; Carvalho, Antonio Carlos Pires

2015-01-01

Ear acupuncture works by reducing painful sensations with analgesic effect through microsystem therapy and has been demonstrated to be as effective as conventional therapies in the control of facial pain. This clinical trial aimed to evaluate the adjuvant action of auricular acupuncture through an observation of the evolution of temporomandibular and masticatory myofascial symptoms in two groups defined by the therapies elected: auricular acupuncture associated with occlusal splint (study) and the use of the occlusal splint plate alone (control). We have selected 20 patients, who were randomly allocated into two groups of ten individuals. Symptoms were evaluated in five different moments, every seven days. We analyzed the orofacial muscle and joint palpation in order to measure the intensity of the experienced pain. Both groups showed a statistically significant decrease in muscle and joint symptoms (p < 0.05). However, comparisons between the groups showed an expressive and significant reduction of symptomatology in the study group (p < 0.05) already on the first week of therapy. According to the results, to the methodological criteria developed and statistical analysis applied, the conclusion is that auricular acupuncture therapy has synergistic action on conventional occlusal splint treatment. It was demonstrated to be effective in the reduction of symptoms in the short term. PMID:26351510

Balance training and center-of-pressure location in participants with chronic ankle instability.

PubMed

Mettler, Abby; Chinn, Lisa; Saliba, Susan A; McKeon, Patrick O; Hertel, Jay

2015-04-01

Chronic ankle instability (CAI) occurs in some people after a lateral ankle sprain and often results in residual feelings of instability and episodes of the ankle's giving way. Compared with healthy people, patients with CAI demonstrated poor postural control and used a more anteriorly and laterally positioned center of pressure (COP) during a single-limb static-balance task on a force plate. Balance training is an effective means of altering traditional COP measures; however, whether the overall location of the COP distribution under the foot also changes is unknown. To determine if the spatial locations of COP data points in participants with CAI change after a 4-week balance-training program. Randomized controlled trial. Laboratory. Thirty-one persons with self-reported CAI. Participants were randomly assigned to a 4-week balance-training program or no balance training. We collected a total of 500 COP data points while participants balanced using a single limb on a force plate during a 10-second trial. The location of each COP data point relative to the geometric center of the foot was determined, and the frequency count in 4 sections (anteromedial, anterolateral, posteromedial, posterolateral) was analyzed for differences between groups. Overall, COP position in the balance-training group shifted from being more anterior to less anterior in both eyes-open trials (before trial = 319.1 ± 165.4, after trial = 160.5 ± 149.5; P = .006) and eyes-closed trials (before trial = 387.9 ± 123.8, after trial = 189.4 ± 102.9; P < .001). The COP for the group that did not perform balance training remained the same in the eyes-open trials (before trial = 214.1 ± 193.3, after trial = 230.0 ± 176.3; P = .54) and eyes-closed trials (before trial = 326.9 ± 134.3, after trial = 338.2 ± 126.1; P = .69). In participants with CAI, the balance-training program shifted the COP location from anterolateral to posterolateral. The program may have repaired some of the damaged sensorimotor system pathways, resulting in a more optimally functioning and less constrained system.

N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

PubMed Central

Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

2013-01-01

Objective To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of hairpulling as measured by the Massachusetts General Hospital–Hairpulling Scale (MGH-HPS). Secondary measures assessed hairpulling severity, automatic versus focused pulling, clinician-rated improvement, and comorbid anxiety and depression. Outcomes were examined using linear mixed models to test the treatment × time interaction in an intention-to-treat population. Results No significant difference between N-acetylcysteine and placebo was found on any of the primary or secondary outcome measures. On several measures of hairpulling, subjects significantly improved with time regardless of treatment assignment. In the NAC group, 25% of subjects were judged as treatment responders, compared to 21% in the placebo group. Conclusions We observed no benefit of NAC for the treatment of children with trichotillomania. Our findings stand in contrast to a previous, similarly designed trial in adults with TTM, which demonstrated a very large, statistically significant benefit of NAC. Based on the differing results of NAC in pediatric and adult TTM populations, the assumption that pharmacological interventions demonstrated to be effective in adults with TTM will be as effective in children, may be inaccurate. This trial highlights the importance of referring children with TTM to appropriate behavioral therapy before initiating pharmacological interventions, as behavioral therapy has demonstrated efficacy in both children and adults with trichotillomania. PMID:23452680

N-Acetylcysteine in the treatment of pediatric trichotillomania: a randomized, double-blind, placebo-controlled add-on trial.

PubMed

Bloch, Michael H; Panza, Kaitlyn E; Grant, Jon E; Pittenger, Christopher; Leckman, James F

2013-03-01

To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of hairpulling as measured by the Massachusetts General Hospital-Hairpulling Scale (MGH-HPS). Secondary measures assessed hairpulling severity, automatic versus focused pulling, clinician-rated improvement, and comorbid anxiety and depression. Outcomes were examined using linear mixed models to test the treatment×time interaction in an intention-to-treat population. No significant difference between N-acetylcysteine and placebo was found on any of the primary or secondary outcome measures. On several measures of hairpulling, subjects significantly improved with time regardless of treatment assignment. In the NAC group, 25% of subjects were judged as treatment responders, compared to 21% in the placebo group. We observed no benefit of NAC for the treatment of children with trichotillomania. Our findings stand in contrast to a previous, similarly designed trial in adults with TTM, which demonstrated a very large, statistically significant benefit of NAC. Based on the differing results of NAC in pediatric and adult TTM populations, the assumption that pharmacological interventions demonstrated to be effective in adults with TTM will be as effective in children, may be inaccurate. This trial highlights the importance of referring children with TTM to appropriate behavioral therapy before initiating pharmacological interventions, as behavioral therapy has demonstrated efficacy in both children and adults with trichotillomania. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Crotalidae polyvalent immune Fab: in patients with North American crotaline envenomation.

PubMed

Keating, Gillian M

2011-04-01

Crotalidae polyvalent immune Fab is an antivenom comprising purified, sheep-derived, Fab IgG fragments and is indicated for use in patients with North American crotaline envenomation. Crotalidae polyvalent immune Fab is produced using four North American snake venoms: Crotalus atrox, Crotalus adamanteus, Crotalus scutulatus, and Agkistrodon piscivorus. Intravenous crotalidae polyvalent immune Fab was effective in patients aged ≥10 years who had minimal or moderate envenomation by a North American crotaline, who presented within 6 hours of the snakebite, and who had progression of the envenomation syndrome, according to the results of two prospective trials. One trial was a noncomparative, multicenter pilot study and the other trial was a randomized, open-label, multicenter trial in which patients received scheduled or 'as needed' administration of crotalidae polyvalent immune Fab after initial control had been achieved. A prospective, postmarketing trial demonstrated the efficacy of crotalidae polyvalent immune Fab in confirmed Crotalus viridis helleri envenomation (indicating cross-protection against a venom not used in its production). Results of these prospective trials are supported by the findings of additional (mainly retrospective) studies demonstrating the efficacy of crotalidae polyvalent immune Fab in patients with crotaline envenomation, including patients with severe envenomation, pediatric patients, and patients with symptoms of neurotoxicity. Despite treatment with crotalidae polyvalent immune Fab, patients may experience delayed-onset or recurrent venom effects (e.g. coagulopathy). Intravenous crotalidae polyvalent immune Fab was generally well tolerated; acute hypersensitivity reactions (e.g. urticaria, rash, pruritus) were the most commonly occurring adverse event. © 2011 Adis Data Information BV. All rights reserved.

The effects of bilingualism on conflict monitoring, cognitive control, and garden-path recovery.

PubMed

Teubner-Rhodes, Susan E; Mishler, Alan; Corbett, Ryan; Andreu, Llorenç; Sanz-Torrent, Monica; Trueswell, John C; Novick, Jared M

2016-05-01

Bilinguals demonstrate benefits on non-linguistic tasks requiring cognitive control-the regulation of mental activity to resolve information-conflict during processing. This "bilingual advantage" has been attributed to the consistent management of two languages, yet it remains unknown if these benefits extend to sentence processing. In monolinguals, cognitive control helps detect and revise misinterpretations of sentence meaning. Here, we test if the bilingual advantage extends to parsing and interpretation by comparing bilinguals' and monolinguals' syntactic ambiguity resolution before and after practicing N-back, a non-syntactic cognitive-control task. Bilinguals outperformed monolinguals on a high-conflict but not a no-conflict version of N-back and on sentence comprehension, indicating that the advantage extends to language interpretation. Gains on N-back conflict trials also predicted comprehension improvements for ambiguous sentences, suggesting that the bilingual advantage emerges across tasks tapping shared cognitive-control procedures. Because the overall task benefits were observed for conflict and non-conflict trials, bilinguals' advantage may reflect increased cognitive flexibility. Copyright © 2016 Elsevier B.V. All rights reserved.

Field evaluation of the efficacy of Mycobacterium bovis BCG vaccine against tuberculosis in goats.

PubMed

Vidal, Enric; Arrieta-Villegas, Claudia; Grasa, Miriam; Mercader, Irene; Domingo, Mariano; Pérez de Val, Bernat

2017-08-17

Control of animal tuberculosis (TB) through vaccination has emerged as a long-term strategy to complement test and slaughter control strategy. A pilot trial under field conditions was conducted in a goat herd with high TB prevalence to assess the efficacy of the Mycobacterium bovis BCG vaccine. Twenty-three goat kids vaccinated with BCG and other 22 unvaccinated control kids were euthanized at 18 months post-vaccination. Gross pathological and histopathological examination of target tissues was performed for detection of tuberculous lesions and assessment of vaccine efficacy. Mycobacterial culture and DNA detection were used to confirm Mycobacterium caprae infection. Vaccination significantly reduced the number of animals with TB lesions compared to unvaccinated controls (35% and 77%, respectively; P < 0.01). This reduction was even higher if only extra-pulmonary infection was considered (17% and 68%, respectively; P < 0.001). This trial demonstrates that BCG vaccination of goats can significantly reduce the TB lesion rates in high disease exposure conditions, indicating that vaccination could contribute to the control of TB in domestic goats.

Chlorhexidine mouthwash reduces plaque and gingivitis.

PubMed

Herrera, David

2013-03-01

Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched along with the reference lists of all selected studies. Only English language studies were included. Randomised controlled clinical trials comparing chlorhexidine (CHX) to placebo/control mouthrinses for oral hygiene in studies of at least four weeks duration were included. Screening, selection and data abstractions were conducted independently by two reviewers. Where possible meta-analysis of weighted mean differences was carried out using fixed or random effects models where appropriate. Thirty studies were included, with 13 studies contributing to the meta-analysis. The meta-analysis found significant differences favouring CHX for a range of indices; the Plaque Index Silness & Löe, Plaque-Index Quigley & Hein (PIQH), the Gingival Index (GI), Papillary BIeeding Index, Bleeding on Marginal Probing and the Lobene Stain Index. Relative to control, the reduction with CHX for plaque was 33% and for gingivitis 26%. CHX rinsing groups demonstrated significantly more staining. In gingivitis patients, CHX mouthrinses together with OH versus placebo, or control mouthrinse provide significant reductions in plaque and gingivitis scores, but a significant increase in staining score.

Landing mechanics during single hop for distance in females following anterior cruciate ligament reconstruction compared to healthy controls.

PubMed

Trigsted, Stephanie M; Post, Eric G; Bell, David R

2017-05-01

To determine possible differences in single-hop kinematics and kinetics in females with anterior cruciate ligament reconstruction compared to healthy controls. A second purpose was to make comparisons between the healthy and reconstructed limbs. Subjects were grouped based on surgical status (33 ACLR patients and 31 healthy controls). 3D motion capture synchronized with force plates was used to capture the landing phase of three successful trials of single hop for distance during a single data collection session. Peak values during the loading phase were analysed. Subjects additionally completed three successful trials of the triple hop for distance Tegner activity scale and International Knee Document Committee 2000 (IKDC). Controls demonstrated greater peak knee flexion and greater internal knee extension moment and hip extension moment than ACLR subjects. Within the ACLR group, the healthy limb exhibited greater peak knee flexion, hip flexion, hip extension moment, single hop and triple hops for distance and normalized quadriceps strength. Patients who undergo anterior cruciate ligament reconstruction land in a more extended posture when compared to healthy controls and compared to their healthy limb. III.

Effects of a Group-Mediated Exercise and Dietary Intervention in the Treatment of Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: Results From the IDEA-P Trial.

PubMed

Focht, Brian C; Lucas, Alexander R; Grainger, Elizabeth; Simpson, Christina; Fairman, Ciaran M; Thomas-Ahner, Jennifer M; Buell, Jackie; Monk, J Paul; Mortazavi, Amir; Clinton, Steven K

2018-04-19

Although androgen-deprivation therapy (ADT) is the foundation of treatment for prostate cancer, the physiological impacts of ADT result in functional decline and enhanced risk of chronic disease and metabolic syndrome. The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is a single-blind, randomized, pilot trial comparing the effects of a group-mediated, cognitive-behavioral (GMCB) exercise and dietary intervention (EX+D) with those of a standard-of-care (SC) control during the treatment of prostate cancer patients undergoing ADT. A total of 32 prostate cancer patients (M age = 66.28, SD = 7.79) undergoing ADT were randomly assigned to the 12-week EX+D intervention (n = 16) or control (n = 16). The primary outcome in IDEA-P was change in mobility performance with secondary outcomes including body composition and muscular strength. Blinded assessment of outcomes were obtained at baseline and at 2- and 3-month follow-ups. Favorable adherence and retention rates were observed, and no serious intervention-related adverse events were documented. Intent-to-treat ANCOVA controlling for baseline value and ADT duration demonstrated that EX+D resulted in significantly greater improvements in mobility performance (p < .02), muscular strength (p < .01), body fat percentage (p < .05), and fat mass (p < .03) at 3-month follow-up, relative to control. Findings from the IDEA-P trial suggest that a GMCB-based EX+D intervention resulted in significant, clinically meaningful improvements in mobility performance, muscular strength, and body composition, relative to controls. Collectively, these results suggest that the EX+D was a safe and well-tolerated intervention for prostate cancer patients on ADT. The utility of implementing this approach in the treatment of prostate cancer patients on ADT should be evaluated in future large-scale efficacy trials. NCT02050906.

Improving Urban African Americans’ Blood Pressure Control through Multi-level Interventions in the Achieving Blood Pressure Control Together (ACT) Study: A Randomized Clinical Trial

PubMed Central

Ephraim, Patti L.; Hill-Briggs, Felicia; Roter, Debra; Bone, Lee; Wolff, Jennifer; Lewis-Boyer, LaPricia; Levine, David; Aboumatar, Hanan; Cooper, Lisa A; Fitzpatrick, Stephanie; Gudzune, Kimberly; Albert, Michael; Monroe, Dwyan; Simmons, Michelle; Hickman, Debra; Purnell, Leon; Fisher, Annette; Matens, Richard; Noronha, Gary; Fagan, Peter; Ramamurthi, Hema; Ameling, Jessica; Charlston, Jeanne; Sam, Tanyka; Carson, Kathryn A.; Wang, Nae-Yuh; Crews, Deidra; Greer, Raquel; Sneed, Valerie; Flynn, Sarah J.; DePasquale, Nicole; Boulware, L. Ebony

2014-01-01

Background Given their high rates of uncontrolled blood pressure, urban African Americans comprise a particularly vulnerable subgroup of persons with hypertension. Substantial evidence has demonstrated the important role of family and community support in improving patients’ management of a variety of chronic illnesses. However, studies of multilevel interventions designed specifically to improve urban African American patients’ blood pressure self-management by simultaneously leveraging patient, family, and community strengths are lacking. Methods/Design We report the protocol of the Achieving Blood Pressure Control Together (ACT) study, a randomized controlled trial designed to study the effectiveness of interventions that engage patient, family, and community-level resources to facilitate urban African American hypertensive patients’ improved hypertension self-management and subsequent hypertension control. African American patients with uncontrolled hypertension receiving health care in an urban primary care clinic will be randomly assigned to receive 1) an educational intervention led by a community health worker alone, 2) the community health worker intervention plus a patient and family communication activation intervention, or 3) the community health worker intervention plus a problem-solving intervention. All participants enrolled in the study will receive and be trained to use a digital home blood pressure machine. The primary outcome of the randomized controlled trial will be patients’ blood pressure control at 12 months. Discussion Results from the ACT study will provide needed evidence on the effectiveness of comprehensive multi-level interventions to improve urban African American patients’ hypertension control. PMID:24956323

Improving urban African Americans' blood pressure control through multi-level interventions in the Achieving Blood Pressure Control Together (ACT) study: a randomized clinical trial.

PubMed

Ephraim, Patti L; Hill-Briggs, Felicia; Roter, Debra L; Bone, Lee R; Wolff, Jennifer L; Lewis-Boyer, LaPricia; Levine, David M; Aboumatar, Hanan J; Cooper, Lisa A; Fitzpatrick, Stephanie J; Gudzune, Kimberly A; Albert, Michael C; Monroe, Dwyan; Simmons, Michelle; Hickman, Debra; Purnell, Leon; Fisher, Annette; Matens, Richard; Noronha, Gary J; Fagan, Peter J; Ramamurthi, Hema C; Ameling, Jessica M; Charlston, Jeanne; Sam, Tanyka S; Carson, Kathryn A; Wang, Nae-Yuh; Crews, Deidra C; Greer, Raquel C; Sneed, Valerie; Flynn, Sarah J; DePasquale, Nicole; Boulware, L Ebony

2014-07-01

Given their high rates of uncontrolled blood pressure, urban African Americans comprise a particularly vulnerable subgroup of persons with hypertension. Substantial evidence has demonstrated the important role of family and community support in improving patients' management of a variety of chronic illnesses. However, studies of multi-level interventions designed specifically to improve urban African American patients' blood pressure self-management by simultaneously leveraging patient, family, and community strengths are lacking. We report the protocol of the Achieving Blood Pressure Control Together (ACT) study, a randomized controlled trial designed to study the effectiveness of interventions that engage patient, family, and community-level resources to facilitate urban African American hypertensive patients' improved hypertension self-management and subsequent hypertension control. African American patients with uncontrolled hypertension receiving health care in an urban primary care clinic will be randomly assigned to receive 1) an educational intervention led by a community health worker alone, 2) the community health worker intervention plus a patient and family communication activation intervention, or 3) the community health worker intervention plus a problem-solving intervention. All participants enrolled in the study will receive and be trained to use a digital home blood pressure machine. The primary outcome of the randomized controlled trial will be patients' blood pressure control at 12months. Results from the ACT study will provide needed evidence on the effectiveness of comprehensive multi-level interventions to improve urban African American patients' hypertension control. Copyright © 2014 Elsevier Inc. All rights reserved.

Safety and immunogenicity of a live attenuated mumps vaccine: a phase I clinical trial.

PubMed

Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, JingJing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan

2014-01-01

Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16-60 years, 5-16 years, 2-5 years and 8-24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control.

Chimpanzees (Pan troglodytes) Transfer Tokens Repeatedly with a Partner to Accumulate Rewards in a Self-Control Task

PubMed Central

Parrish, Audrey E.; Perdue, Bonnie M.; Evans, Theodore A.; Beran, Michael J.

2013-01-01

There has been extensive research investigating self-control in humans and nonhuman animals, yet we know surprisingly little about how one’s social environment influences self-control. The present study examined the self-control of chimpanzees in a task that required active engagement with conspecifics. The task consisted of transferring a token back and forth with a partner animal in order to accumulate food rewards, one item per token transfer. Self-control was required because at any point in the trial, either chimpanzee could obtain their accumulated rewards, but doing so discontinued the food accumulation and ended the trial for both individuals. Chimpanzees readily engaged the task and accumulated the majority of available rewards before ending each trial, and they did so across a number of conditions that varied the identity of the partner, the presence/absence of the experimenter, and the means by which they could obtain rewards. A second experiment examined chimpanzees’ self-control when given the choice between immediately available food items and a potentially larger amount of rewards that could be obtained by engaging the token transfer task with a partner. Chimpanzees were flexible in their decision-making in this test, typically choosing the option representing the largest amount of food, even if it involved delayed accumulation of the rewards via the token transfer task. These results demonstrate that chimpanzees can exhibit self-control in situations involving social interactions, and they encourage further research into this important aspect of the self-control scenario. PMID:23381691

Motivational Modulation of Self-Initiated and Externally Triggered Movement Speed Induced by Threat of Shock: Experimental Evidence for Paradoxical Kinesis in Parkinson’s Disease

PubMed Central

McDonald, Louise M.; Griffin, Harry J.; Angeli, Aikaterini; Torkamani, Mariam; Georgiev, Dejan; Jahanshahi, Marjan

2015-01-01

Background Paradoxical kinesis has been observed in bradykinetic people with Parkinson’s disease. Paradoxical kinesis occurs in situations where an individual is strongly motivated or influenced by relevant external cues. Our aim was to induce paradoxical kinesis in the laboratory. We tested whether the motivation of avoiding a mild electric shock was sufficient to induce paradoxical kinesis in externally-triggered and self-initiated conditions in people with Parkinson’s disease tested on medication and in age-matched controls. Methods Participants completed a shock avoidance behavioural paradigm in which half of the trials could result in a mild electric shock if the participant did not move fast enough. Half of the trials of each type were self-initiated and half were externally-triggered. The criterion for avoiding shock was a maximum movement time, adjusted according to each participant’s performance on previous trials using a staircase tracking procedure. Results On trials with threat of shock, both patients with Parkinson’s disease and controls had faster movement times compared to no potential shock trials, in both self-initiated and externally-triggered conditions. The magnitude of improvement of movement time from no potential shock to potential shock trials was positively correlated with anxiety ratings. Conclusions When motivated to avoid mild electric shock, patients with Parkinson’s disease, similar to healthy controls, showed significant speeding of movement execution. This was observed in both self-initiated and externally-triggered versions of the task. Nevertheless, in the ET condition the improvement of reaction times induced by motivation to avoid shocks was greater for the PD patients than controls, highlighting the value of external cues for movement initiation in PD patients. The magnitude of improvement from the no potential shock to the potential shock trials was associated with the threat-induced anxiety. This demonstration of paradoxical kinesis in the laboratory under both self-initiated and externally-triggered conditions has implications for motivational and attentional enhancement of movement speed in Parkinson’s disease. PMID:26284366

Self-Management and Clinical Decision Support for Patients With Complex Chronic Conditions Through the Use of Smartphone-Based Telemonitoring: Randomized Controlled Trial Protocol

PubMed Central

Ware, Patrick; Logan, Alexander G; Cafazzo, Joseph A; Chapman, Kenneth R; Segal, Phillip; Ross, Heather J

2017-01-01

Background The rising prevalence of chronic illnesses hinders the sustainability of the health care system because of the high cost of frequent hospitalizations of patients with complex chronic conditions. Clinical trials have demonstrated that telemonitoring can improve health outcomes, but they have generally been limited to single conditions such as diabetes, hypertension, or heart failure. Few studies have examined the impact of telemonitoring on complex patients with multiple chronic conditions, although these patients may benefit the most from this technology. Objective The aim of this study is to investigate the impact of a smartphone-based telemonitoring system on the clinical care and health outcomes of complex patients across several chronic conditions. Methods A mixed-methods, 6-month randomized controlled trial (RCT) of a smartphone-based telemonitoring system is being conducted in specialty clinics. The study will include patients who have been diagnosed with one or more of any of the following conditions: heart failure, chronic obstructive pulmonary disease, chronic kidney disease, uncontrolled hypertension, or insulin-requiring diabetes. The primary outcome will be the health status of patients as measured with SF-36. Patients will be randomly assigned to either the control group receiving usual care (n=73) or the group using the smartphone-based telemonitoring system in addition to usual care (n=73). Results Participants are currently being recruited for the trial. Data collection is anticipated to be completed by the fall of 2018. Conclusions This RCT will be among the first trials to provide evidence of the impact of telemonitoring on costs and health outcomes of complex patients who may have multiple chronic conditions. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 41238563; http://www.isrctn.com/ISRCTN41238563 (Archived by WebCite at http://www.webcitation.org/6ug2Sk0af) and Clinicaltrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852 (Archived by WebCite at http://www.webcitation.org/6uvjNosBC) PMID:29162557

Management of Hypertension in Diabetic Nephropathy: How Low Should We Go?

PubMed

Sternlicht, Hillel; Bakris, George L

2016-01-01

Hypertension is a frequent comorbidity often following the development of diabetic nephropathy among individuals with type 1 diabetes and affecting most patients with type 2 diabetes at the time of diagnosis. Multiple prospective randomized placebo-controlled trials demonstrate that tight blood pressure control among patients with diabetic nephropathy reduces the rates of macrovascular and microvascular complications. While randomized trials exist and support a blood pressure goal of <140/90 mm Hg for patients with nondiabetic kidney disease, there are no prospective data regarding a specific blood pressure goal on progression of diabetic nephropathy. Retrospective data analyses from trials show a linear relationship between either baseline or achieved study blood pressure and progression of nephropathy. Very high albuminuria is a hallmark of diabetic nephropathy with reductions by either angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blocker (ARB) monotherapy associated with slowed nephropathy progression. However, combination antihypertensive therapy, while decreasing proteinuria, augments the risk of hyperkalemia, hypotension, and kidney dysfunction. Given the lack of trial data for a BP goal among patients with diabetic nephropathy, prospective trials are needed to define the optimal blood pressure necessary to preserve kidney function. At present, guideline blood pressure goals of less than 140/90 mm Hg and the use of ACEi or ARB therapy for those with more than 300 mg of albuminuria are mandated. © 2016 S. Karger AG, Basel.

[Psychostimulants for late life depression].

PubMed

Delsalle, P; Schuster, J-P; von Gunten, A; Limosin, F

2017-11-28

The use of psychostimulants in the treatment of depressive disorders is receiving renewed interest. Recent publications suggest a particular interest of psychostimulants in the treatment of depression in the elderly. The aim of this article is to review the literature on the role of psychostimulants in the treatment of depression in older adults. The literature review focused on efficacy and tolerability studies of psychostimulants in the treatment of depression for the elderly that were published between 1980 and 2016. The only inclusion criterion applied was an average age of the sample studied greater than or equal to 60 years. Overall, 12 trials were selected: 3 controlled trials and 9 uncontrolled trials. Of the 3 controlled trials, one compared parallel groups and the other two were cross-tests. Among the psychostimulants, methylphenidate was the most studied molecule. The trials demonstrate an efficacy of this molecule in particular as an add-on therapy in old-age depression but for the most part with a level of proof that remains insufficient. The small size of the samples and the methodological limitations of the studies obviate the possibility of extracting definitive conclusions concerning the place of psychostimulants in the treatment of depression in the elderly. Further studies are required in particular in the treatment of resistant depressive episodes. Copyright © 2017 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.