Kernel PLS Estimation of Single-trial Event-related Potentials

NASA Technical Reports Server (NTRS)

Rosipal, Roman; Trejo, Leonard J.

2004-01-01

Nonlinear kernel partial least squaes (KPLS) regressior, is a novel smoothing approach to nonparametric regression curve fitting. We have developed a KPLS approach to the estimation of single-trial event related potentials (ERPs). For improved accuracy of estimation, we also developed a local KPLS method for situations in which there exists prior knowledge about the approximate latency of individual ERP components. To assess the utility of the KPLS approach, we compared non-local KPLS and local KPLS smoothing with other nonparametric signal processing and smoothing methods. In particular, we examined wavelet denoising, smoothing splines, and localized smoothing splines. We applied these methods to the estimation of simulated mixtures of human ERPs and ongoing electroencephalogram (EEG) activity using a dipole simulator (BESA). In this scenario we considered ongoing EEG to represent spatially and temporally correlated noise added to the ERPs. This simulation provided a reasonable but simplified model of real-world ERP measurements. For estimation of the simulated single-trial ERPs, local KPLS provided a level of accuracy that was comparable with or better than the other methods. We also applied the local KPLS method to the estimation of human ERPs recorded in an experiment on co,onitive fatigue. For these data, the local KPLS method provided a clear improvement in visualization of single-trial ERPs as well as their averages. The local KPLS method may serve as a new alternative to the estimation of single-trial ERPs and improvement of ERP averages.

F157. HIERARCHICAL PREDICTION ERRORS DURING AUDITORY MISMATCH UNDER PHARMACOLOGICAL MANIPULATIONS: A COMPUTATIONAL SINGLE-TRIAL EEG ANALYSIS

PubMed Central

Weber, Lilian; Diaconescu, Andreea; Tomiello, Sara; Schöbi, Dario; Iglesias, Sandra; Mathys, Christoph; Haker, Helene; Stefanics, Gabor; Schmidt, André; Kometer, Michael; Vollenweider, Franz X; Stephan, Klaas Enno

2018-01-01

Abstract Background A central theme of contemporary neuroscience is the notion that the brain embodies a generative model of its sensory inputs to infer on the underlying environmental causes, and that it uses hierarchical prediction errors (PEs) to continuously update this model. In two pharmacological EEG studies, we investigate trial-wise hierarchical PEs during the auditory mismatch negativity (MMN), an electrophysiological response to unexpected events, which depends on NMDA-receptor mediated plasticity and has repeatedly been shown to be reduced in schizophrenia. Methods Study1: Reanalysis of 64 channel EEG data from a previously published MMN study (Schmidt et al., 2012) using a placebo-controlled, within-subject design (N=19) to examine the effect of S-ketamine. Study2: 64 channel EEG data recorded during MMN (between subjects, double-blind, placebo-controlled design, N=73), to examine the effects of amisulpride and biperiden. Using the Hierarchical Gaussian Filter, a Bayesian learning model, we extracted trial-by-trial PE estimates on two hierarchical levels. These served as regressors in a GLM of trial-wise EEG signals at the sensor level. Results We find strong correlations of EEG with both PEs in both samples: lower-level PEs show effects early on (Study1: 133ms post-stimulus, Study2: 177ms), higher-level PEs later (Study1: 240ms, Study2: 450ms). The temporal order of these signatures thus mimics the hierarchical relationship of the PEs, as proposed by our computational model, where lower level beliefs need to be updated before learning can ensue on higher levels. Ketamine significantly reduced the representation of the higher-level PE in Study1. (Study2 has not been unblinded.) Discussion These studies present first evidence for hierarchical PEs during MMN and demonstrate that single-trial analyses guided by a computational model can distinguish different types (levels) of PEs, which are differentially linked to neuromodulators of demonstrated relevance for schizophrenia. Our analysis approach thus provides better mechanistic interpretability of pharmacological MMN studies, which will hopefully support the development of computational assays for diagnosis and treatment predictions in schizophrenia.

Global signal modulation of single-trial fMRI response variability: Effect on positive vs negative BOLD response relationship.

PubMed

Mayhew, S D; Mullinger, K J; Ostwald, D; Porcaro, C; Bowtell, R; Bagshaw, A P; Francis, S T

2016-06-01

In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR-NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of average responses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of BCAA, arginine and carbohydrate combined drink on post-exercise biochemical response and psychological condition.

PubMed

Hsu, Mei-Chich; Chien, Kuei-Yu; Hsu, Cheng-Chen; Chung, Chia-Jung; Chan, Kuei-Hui; Su, Borcherng

2011-04-30

This study investigated the effects of BCAA, arginine and carbohydrate combined beverage (BCAA Drink) on biochemical responses and psychological conditions during recovery after a single bout of exhaustive exercise. Fourteen healthy males were assigned to drink either BCAA Drink (BA trial) or placebo (PL trial) on two sessions separated by 2 weeks. Blood samples of each subject were collected before exercise, 0, 10, 20, 40, 60, 120 min and 24 h after exercise. No significant differences in the levels of lactate, ammonia, creatine kinase and glycerol between the two groups were observed at any of the time points. However, the levels of glucose and insulin were significantly higher in the BA trial as compared to those in the PL trial at the 40 and 60 min recovery points. Furthermore, the testosterone-to-cortisol ratio at the 120 min recovery point was significantly higher in the BA trial as compared to that in the PL trial. The results indicate the occurrence of anabolic response during the recovery period. The benefit of BCAA Drink was also performed by Profile of Mood States to assess the psychological condition. Fatigue score increased immediately at exhaustion in both groups, but the decrease in the fatigue score at 120 min recovery point was significant only in BA trial. These data indicate that a single bout of exhaustive exercise enhanced the feeling of fatigue. The detrimental consequence was reduced by an ingestion of BCAA Drink.

Spatiotemporal dynamics of random stimuli account for trial-to-trial variability in perceptual decision making

PubMed Central

Park, Hame; Lueckmann, Jan-Matthis; von Kriegstein, Katharina; Bitzer, Sebastian; Kiebel, Stefan J.

2016-01-01

Decisions in everyday life are prone to error. Standard models typically assume that errors during perceptual decisions are due to noise. However, it is unclear how noise in the sensory input affects the decision. Here we show that there are experimental tasks for which one can analyse the exact spatio-temporal details of a dynamic sensory noise and better understand variability in human perceptual decisions. Using a new experimental visual tracking task and a novel Bayesian decision making model, we found that the spatio-temporal noise fluctuations in the input of single trials explain a significant part of the observed responses. Our results show that modelling the precise internal representations of human participants helps predict when perceptual decisions go wrong. Furthermore, by modelling precisely the stimuli at the single-trial level, we were able to identify the underlying mechanism of perceptual decision making in more detail than standard models. PMID:26752272

Intradiscal Platelet-Rich Plasma Injection for Chronic Discogenic Low Back Pain: Preliminary Results from a Prospective Trial.

PubMed

Levi, David; Horn, Scott; Tyszko, Sara; Levin, Josh; Hecht-Leavitt, Charles; Walko, Edward

2016-06-01

Platelet-rich plasma (PRP) has been found to be effective for a variety of musculoskeletal conditions. The treatment of discogenic pain with PRP is under investigation. To assess changes in pain and function in patients with discogenic low back pain after an intradiscal injection of PRP. Prospective trial. Patients were diagnosed with discogenic low back pain by clinical means, imaging, and exclusion of other structures. Provocation discography was used in a minority of the patients. Patients underwent a single treatment of intradiscal injection of PRP at one or multiple levels. Patients were considered a categorical success if they achieved at least 50% improvement in the visual analog score and 30% decrease in the Oswestry Disability Index at 1, 2, and 6 months post-treatment. 22 patients underwent intradiscal PRP. Nine patients underwent a single level injection, ten at 2 levels, two at 3 levels, and one at 5 levels. Categorical success rates were as follows: 1 month: 3/22 = 14% (95% CI 0% to 28%), 2 months: 7/22 = 32% (95% CI 12% to 51%), 6 months: 9/19 = 47% (95% CI 25% to 70%). This trial demonstrates encouraging preliminary 6 month findings, using strict categorical success criteria, for intradiscal PRP as a treatment for presumed discogenic low back pain. Randomized placebo controlled trials are needed to further evaluate the efficacy of this treatment. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Summary of Meta-Analyses Dealing with Single-Row versus Double-Row Repair Techniques for Rotator Cuff Tears

PubMed Central

Spiegl, U.J.; Euler, S.A.; Millett, P.J.; Hepp, P.

2016-01-01

Background: Several meta-analyses of randomized clinical trials have been performed to analyze whether double-row (DR) rotator cuff repair (RCR) provides superior clinical outcomes and structural healing compared to single-row (SR) repair. The purpose of this study was to sum up the results of meta-analysis comparing SR and DR repair with respect on clinical outcomes and re-tear rates. Methods: A literature search was undertaken to identify all meta-analyses dealing with randomized controlled trials comparing clinical und structural outcomes after SR versus DR RCR. Results: Eight meta-analyses met the eligibility criteria: two including Level I studies only, five including both Level I and Level II studies, and one including additional Level III studies. Four meta-analyses found no differences between SR and DR RCR for patient outcomes, whereas four favored DR RCR for tears greater than 3 cm. Two meta-analyses found no structural healing differences between SR and DR RCR, whereas six found DR repair to be superior for tears greater than 3 cm tears. Conclusion: No clinical differences are seen between single-row and double-row repair for small and medium rotator cuff tears after a short-term follow-up period with a higher re-tear rate following single-row repairs. There seems to be a trend to superior results with double-row repair in large to massive tear sizes. PMID:27708735

Task-dependent response conflict monitoring and cognitive control in anterior cingulate and dorsolateral prefrontal cortices.

PubMed

Kim, Chobok; Chung, Chongwook; Kim, Jeounghoon

2013-11-06

Previous experience affects our behavior in terms of adjustments. It has been suggested that the conflict monitor-controller system implemented in the prefrontal cortex plays a critical role in such adjustments. Previous studies suggested that there exists multiple conflict monitor-controller systems associated with the level of information (i.e., stimulus and response levels). In this study, we sought to test whether different types of conflicts occur at the same information processing level (i.e., response level) are independently processed. For this purpose, we designed a task paradigm to measure two different types of response conflicts using color-based and location-based conflict stimuli and measured the conflict adaptation effects associated with the two types of conflicts either independently (i.e., single conflict conditions) or simultaneously (i.e., a double-conflict condition). The behavioral results demonstrated that performance on current incongruent trials was faster only when the preceding trial was the same type of response conflict regardless of whether they included a single- or double-conflict. Imaging data also showed that anterior cingulate and dorsolateral prefrontal cortices operate in a task-specific manner. These findings suggest that there may be multiple monitor-controller loops for color-based and location-based conflicts even at the same response level. Importantly, our results suggest that double-conflict processing is qualitatively different from single-conflict processing although double-conflict shares the same sources of conflict with two single-conflict conditions. © 2013 Published by Elsevier B.V.

Insulin and oral agents for managing cystic fibrosis-related diabetes.

PubMed

Onady, Gary M; Stolfi, Adrienne

2016-04-18

The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or oral glucose tolerance tests greater than 11.11 mmol/liter (200 mg/deciliter) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%. To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 18 February 2016. Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes. Two authors independently extracted data and assessed the risk of bias in the included studies. The searches identified 22 trials (34 references). Four trials (200 participants) are included: one short-term single-center trial (n = 7) comparing insulin with oral repaglinide and no medication in people with cystic fibrosis-related diabetes and normal fasting glucose; one long-term multicenter trial (n = 100, 74 of whom had cystic fibrosis-related diabetes) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (n = 73) comparing insulin with oral repaglinide; and one 12-week single-center trial (n = 20) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin.Two trials with data for the comparison of insulin to placebo did not report any significant differences between groups for the primary outcomes of blood glucose levels, lung function and nutritional status. This was also true for the single trial with data for the comparison of repaglinide to placebo. Two trials (one lasting one year and one lasting two years) contributed data for the comparison of insulin versus repaglinide. There were no significant differences for the primary outcomes at any time point, except at one year (in the two-year trial) when the insulin group had significant improvement in z score for body mass index compared to the repaglinide group. The single trial comparing glargine to neutral protamine Hagedorn insulin also did not report any significant differences in the review's primary outcomes. A few cases of hypoglycemia were seen in three out of the four trials (none in the longest trial), but these events resolved without further treatment.There was an unclear risk of bias from randomization and allocation concealment in two of the four included trials as the authors did not report any details; in the remaining two studies details for randomization led to a low risk of bias, but only one had sufficient details on allocation concealment to allow a low risk judgement, the second was unclear. There was a high risk from blinding for all trials (except for the comparison of oral repaglinide versus placebo) due to the nature of the interventions. Complete data for all outcomes were not available from any trial leading to a high risk of reporting bias. The amounts of insulin and repaglinide administered were not comparable and this may lead to bias in the results. None of the included trials were powered to show a significant improvement in lung function. This review has not found any significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycemic agents have a distinct advantage over one another in controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority.There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further trials need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy.

Knowledge translation studies in paediatric emergency medicine: A systematic review of the literature.

PubMed

Wilson, Catherine L; Johnson, David; Oakley, Ed

2016-02-01

Systematic review of knowledge translation studies focused on paediatric emergency care to describe and assess the interventions used in emergency department settings. Electronic databases were searched for knowledge translation studies conducted in the emergency department that included the care of children. Two researchers independently reviewed the studies. From 1305 publications identified, 15 studies of varied design were included. Four were cluster-controlled trials, two patient-level randomised controlled trials, two interrupted time series, one descriptive study and six before and after intervention studies. Knowledge translation interventions were predominantly aimed at the treating clinician, with some targeting the organisation. Studies assessed effectiveness of interventions over 6-12 months in before and after studies, and 3-28 months in cluster or patient level controlled trials. Changes in clinical practice were variable, with studies on single disease and single treatments in a single site showing greater improvement. Evidence for effective methods to translate knowledge into practice in paediatric emergency medicine is fairly limited. More optimal study designs with more explicit descriptions of interventions are needed to facilitate other groups to effectively apply these procedures in their own setting. © 2016 The Authors Journal of Paediatrics and Child Health © 2016 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Long-term Evaluation of Cervical Disc Arthroplasty with the Mobi-C© Cervical Disc: A Randomized, Prospective, Multicenter Clinical Trial with Seven-Year Follow-up.

PubMed

Radcliff, Kris; Davis, Reginald J; Hisey, Michael S; Nunley, Pierce D; Hoffman, Gregory A; Jackson, Robert J; Bae, Hyun W; Albert, Todd; Coric, Dom

2017-01-01

Cervical total disc replacement (TDR) is an increasingly accepted procedure for the treatment of symptomatic cervical degenerative disc disease. Multiple Level I evidence clinical trials have established cervical TDR to be a safe and effective procedure in the short-term. The objective of this study is to provide a long-term assessment of TDR versus anterior discectomy and fusion for the treatment of one- and two-level disc disease. This study was a continuation of a prospective, multicenter, randomized, US FDA IDE clinical trial comparing cervical TDR with the Mobi-C © Cervical Disc versus ACDF through 7 years follow-up. Inclusion criteria included a diagnosis of symptomatic cervical degenerative disc disease at one or two cervical levels. TDR patients were treated using a Mobi-C © artificial disc (Zimmer Biomet, Austin TX, USA). ACDF with allograft and anterior plate was used as a control treatment. Outcome measures were collected preoperatively and postoperatively at 6 weeks, at 3, 6, 12, 18 months, annually through 60 months, and at 84 months. Measured outcomes included Overall success, Neck Disability Index (NDI), VAS neck and arm pain, segmental range of motion (ROM), patient satisfaction, SF-12 MCS/PCS, major complications, and subsequent surgery rate. The primary endpoint was an FDA composite definition of success comprising clinical improvement and an absence of major complications and secondary surgery events. A total of 599 patients were enrolled and treated, with 164 treated with one-level TDR, 225 treated with two-level TDR, 81 treated with one-level ACDF, and 105 treated with two-level ACDF. At seven years, follow-up rates ranged from 73.5% to 84.4% (overall 80.2%).The overall success rates of two level TDR and ACDF patients were 60.8% and 34.2%, respectively (p<0.0001). The overall success rates of one level TDR and ACDF patients were 55.2% and 50%, respectively (p>0.05). Both the single and two level TDR and ACDF groups showed significant improvement from baseline NDI scores, VAS neck and arm pain scores, and SF-12 MCS/PCS scores (p<0.0001). In the single level cohort, there was an increased percentage of TDR patients who reported themselves as "very satisfied" (TDR 90.9% vs ACDF 77.8%; p= 0.028). There was a lower rate of adjacent level secondary surgery in the single level TDR patients (3.7%) versus the ACDF patients (13.6%; p = 0.007).In the two level TDR group, the NDI success rate was significantly greater in the TDR group (TDR: 79.0% vs. ACDF: 58.0%; p=0.001). There was significantly more improvement in NDI change score at 7 years in the TDR patients versus ACDF. The TDR group had a significantly higher rate of patients who were "very satisfied" with their treatment compared to the ACDF group (TDR: 85.9% vs. ACDF: 73.9%). The rate of subsequent surgery at the index level was significantly lower in the TDR group compared to the ACDF group (TDR: 4.4% vs. ACDF: 16.2%; p=0.001). The rate of adjacent level secondary surgery was significantly lower in the two level TDR (4.4%) patients compared to the ACDF (11.3%; p=0.03) patients. In both single and two level cohorts, the percentage of patients with worse NDI (2.5%-3.8% of two level surgeries and 1.2%-2.5% of single level surgeries) or worse neck pain (5%-6.8% of the two level surgeries and 1.3% - 3.8% of the single level surgeries) was strikingly low in both groups but trended lower in the TDR patients. At seven years, the composite success analysis demonstrated clinical superiority of two level TDR over ACDF and non-inferiority of single level TDR versus ACDF. There were lower rates of secondary surgery and higher adjacent level disc survivorship in both groups. Both surgeries were remarkably effective in alleviating pain relative to baseline and the rate of patients with worse disability or neck pain was surprisingly low. Overall, greater than 95% of patients (from both groups) who underwent TDR and 88% of patients who underwent ACDF were "very satisfied" at seven years. The differences in clinical effectiveness of TDR versus ACDF becomes more apparent as treatment increases from one to two levels, indicating a significant benefit for TDR over ACDF for two-level procedures. The Mobi-C Clinical Trial (ClinicalTrials.gov registration number: NCT00389597) was conducted at 24 sites in the US and was approved by the Institutional Review Board, Research Ethics Committee, or local equivalent of each participating site. 1.

Methods for Synthesizing Findings on Moderation Effects Across Multiple Randomized Trials

PubMed Central

Brown, C Hendricks; Sloboda, Zili; Faggiano, Fabrizio; Teasdale, Brent; Keller, Ferdinand; Burkhart, Gregor; Vigna-Taglianti, Federica; Howe, George; Masyn, Katherine; Wang, Wei; Muthén, Bengt; Stephens, Peggy; Grey, Scott; Perrino, Tatiana

2011-01-01

This paper presents new methods for synthesizing results from subgroup and moderation analyses across different randomized trials. We demonstrate that such a synthesis generally results in additional power to detect significant moderation findings above what one would find in a single trial. Three general methods for conducting synthesis analyses are discussed, with two methods, integrative data analysis, and parallel analyses, sharing a large advantage over traditional methods available in meta-analysis. We present a broad class of analytic models to examine moderation effects across trials that can be used to assess their overall effect and explain sources of heterogeneity, and present ways to disentangle differences across trials due to individual differences, contextual level differences, intervention, and trial design. PMID:21360061

Methods for synthesizing findings on moderation effects across multiple randomized trials.

PubMed

Brown, C Hendricks; Sloboda, Zili; Faggiano, Fabrizio; Teasdale, Brent; Keller, Ferdinand; Burkhart, Gregor; Vigna-Taglianti, Federica; Howe, George; Masyn, Katherine; Wang, Wei; Muthén, Bengt; Stephens, Peggy; Grey, Scott; Perrino, Tatiana

2013-04-01

This paper presents new methods for synthesizing results from subgroup and moderation analyses across different randomized trials. We demonstrate that such a synthesis generally results in additional power to detect significant moderation findings above what one would find in a single trial. Three general methods for conducting synthesis analyses are discussed, with two methods, integrative data analysis and parallel analyses, sharing a large advantage over traditional methods available in meta-analysis. We present a broad class of analytic models to examine moderation effects across trials that can be used to assess their overall effect and explain sources of heterogeneity, and present ways to disentangle differences across trials due to individual differences, contextual level differences, intervention, and trial design.

Techniques for extracting single-trial activity patterns from large-scale neural recordings

PubMed Central

Churchland, Mark M; Yu, Byron M; Sahani, Maneesh; Shenoy, Krishna V

2008-01-01

Summary Large, chronically-implanted arrays of microelectrodes are an increasingly common tool for recording from primate cortex, and can provide extracellular recordings from many (order of 100) neurons. While the desire for cortically-based motor prostheses has helped drive their development, such arrays also offer great potential to advance basic neuroscience research. Here we discuss the utility of array recording for the study of neural dynamics. Neural activity often has dynamics beyond that driven directly by the stimulus. While governed by those dynamics, neural responses may nevertheless unfold differently for nominally identical trials, rendering many traditional analysis methods ineffective. We review recent studies – some employing simultaneous recording, some not – indicating that such variability is indeed present both during movement generation, and during the preceding premotor computations. In such cases, large-scale simultaneous recordings have the potential to provide an unprecedented view of neural dynamics at the level of single trials. However, this enterprise will depend not only on techniques for simultaneous recording, but also on the use and further development of analysis techniques that can appropriately reduce the dimensionality of the data, and allow visualization of single-trial neural behavior. PMID:18093826

Spinal cord stimulation for axial low back pain: a prospective, controlled trial comparing dual with single percutaneous electrodes.

PubMed

North, Richard B; Kidd, David H; Olin, John; Sieracki, Jeffrey M; Farrokhi, Farrokh; Petrucci, Loredana; Cutchis, Protagoras N

2005-06-15

A prospective, controlled, clinical trial comparing single and dual percutaneous electrodes in the treatment of axial low back pain from failed back surgery syndrome. To clarify technical requirements and test the hypothesis that placing two linear arrays in parallel, thereby doubling the number of contacts, improves outcome. Technical improvements have enhanced outcomes of spinal cord stimulation for chronic axial low back pain. Dual, parallel electrodes reportedly improve these outcomes. Acting as their own controls, 20 patients who passed screening with single, 4-contact electrodes received permanent dual, 4-contact electrodes with 7- or 10-mm intercontact distances at the same vertebral level(s). We quantified and compared the technical and clinical results of the single and dual electrodes, adjusting stimulation parameters to specific psychophysical thresholds. Single electrodes provided significant (P < 0.01) advantages in patient- and computer-calculated ratings of pain coverage by paresthesias and in the scaled amplitude necessary to cover the low back, compared with dual 7-mm electrodes. Slight advantages without statistical significance were observed for the single over the dual 10-mm electrodes. Amplitude requirements were significantly lower for the single electrode than for either dual electrode. At long-term follow-up, 53% of patients met the criteria for clinical success. While we observed disadvantages for dual electrodes in treating axial low back pain, we achieved technical success with single or dual electrodes in most patients and maintained this success clinically with dual electrodes in 53%.

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

PubMed

Ray, Kausik K; Landmesser, Ulf; Leiter, Lawrence A; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P T; Turner, Traci; Visseren, Frank L J; Wijngaard, Peter; Wright, R Scott; Kastelein, John J P

2017-04-13

In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers. We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240. A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg inclisiran regimen produced the greatest reduction in LDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran. In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company; ORION-1 ClinicalTrials.gov number, NCT02597127 .).

Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview.

PubMed

Woolacott, Nerys; Corbett, Mark; Jones-Diette, Julie; Hodgson, Robert

2017-10-01

Regulatory authorities are approving innovative therapies with limited evidence. Although this level of data is sufficient for the regulator to establish an acceptable risk-benefit balance, it is problematic for downstream health technology assessment, where assessment of cost-effectiveness requires reliable estimates of effectiveness relative to existing clinical practice. Some key issues associated with a limited evidence base include using data, from nonrandomized studies, from small single-arm trials, or from single-center trials; and using surrogate end points. We examined these methodological challenges through a pragmatic review of the available literature. Methods to adjust nonrandomized studies for confounding are imperfect. The relative treatment effect generated from single-arm trials is uncertain and may be optimistic. Single-center trial results may not be generalizable. Surrogate end points, on average, overestimate treatment effects. Current methods for analyzing such data are limited, and effectiveness claims based on these suboptimal forms of evidence are likely to be subject to significant uncertainty. Assessments of cost-effectiveness, based on the modeling of such data, are likely to be subject to considerable uncertainty. This uncertainty must not be underestimated by decision makers: methods for its quantification are required and schemes to protect payers from the cost of uncertainty should be implemented. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Double versus single high-dose melphalan 200 mg/m2 and autologous stem cell transplantation for multiple myeloma: a region-based study in 484 patients from the Nordic area

PubMed Central

Björkstrand, Bo; Klausen, Tobias W.; Remes, Kari; Gruber, Astrid; Knudsen, Lene M.; Bergmann, Olav J.; Lenhoff, Stig; Johnsen, Hans E.

2009-01-01

Autologous stem cell transplantation is still considered the standard of care in young patients with multiple myeloma (MM). This disease is the most common indication for high-dose therapy (HDT) supported by hematopoietic stem cell transplantation and much data support the benefit of this procedure. Results of randomized studies are in favor of tandem autologous transplantation although the effect on overall survival is unclear. Based on sequential registration trials in the Nordic area, we aimed to evaluate the outcome of conventional single or double HDT. During 1994–2000 we registered a total of 484 previously untreated patients under the age of 60 years at diagnosis who on a regional basis initially were treated with single [Trial NMSG #5/94 and #7/98 (N=383)] or double [Trial Huddinge Karolinska Turku Herlev (N=101)] high-dose melphalan (200 mg/m2) therapy supported by autologous stem cell transplantation. A complete or very good partial response was achieved by 40% of patients in the single transplant group and 60% of patients in the double transplant group (p=0.0006). The probability of surviving progression free for five years after the diagnosis was 25% (95% CL 18–32%) in the singletransplant group and 46% (95% CL 33–55%) in the double transplant group (p=0.0014). The estimated overall five-year survival rate was 60% in the single transplant group and 64% in the doubletransplant (p=0.9). In a multivariate analysis of variables, including single versus double transplantation, β2 microglobulin level, age, sex and disease stage, only β2 microglobulin level was predictive for overall survival (p>0.0001) and progression free survival (p=0.001). In accordance with these results, a 1:1 case-control matched comparison between double and single transplantation did not identify significant differences in overall and progression free survival. In this retrospective analysis up front double transplantation with melphalan (200 mg/m2) as compared to single transplantation did not seem to improve the final outcome among patients in the Nordic area. These data are in accordance with recent publications from the Bologna 96 trial indicating that a second transplant should not be recommended up front as standard care.

Mental workload during n-back task-quantified in the prefrontal cortex using fNIRS.

PubMed

Herff, Christian; Heger, Dominic; Fortmann, Ole; Hennrich, Johannes; Putze, Felix; Schultz, Tanja

2013-01-01

When interacting with technical systems, users experience mental workload. Particularly in multitasking scenarios (e.g., interacting with the car navigation system while driving) it is desired to not distract the users from their primary task. For such purposes, human-machine interfaces (HCIs) are desirable which continuously monitor the users' workload and dynamically adapt the behavior of the interface to the measured workload. While memory tasks have been shown to elicit hemodynamic responses in the brain when averaging over multiple trials, a robust single trial classification is a crucial prerequisite for the purpose of dynamically adapting HCIs to the workload of its user. The prefrontal cortex (PFC) plays an important role in the processing of memory and the associated workload. In this study of 10 subjects, we used functional Near-Infrared Spectroscopy (fNIRS), a non-invasive imaging modality, to sample workload activity in the PFC. The results show up to 78% accuracy for single-trial discrimination of three levels of workload from each other. We use an n-back task (n ∈ {1, 2, 3}) to induce different levels of workload, forcing subjects to continuously remember the last one, two, or three of rapidly changing items. Our experimental results show that measuring hemodynamic responses in the PFC with fNIRS, can be used to robustly quantify and classify mental workload. Single trial analysis is still a young field that suffers from a general lack of standards. To increase comparability of fNIRS methods and results, the data corpus for this study is made available online.

Mental workload during n-back task—quantified in the prefrontal cortex using fNIRS

PubMed Central

Herff, Christian; Heger, Dominic; Fortmann, Ole; Hennrich, Johannes; Putze, Felix; Schultz, Tanja

2014-01-01

When interacting with technical systems, users experience mental workload. Particularly in multitasking scenarios (e.g., interacting with the car navigation system while driving) it is desired to not distract the users from their primary task. For such purposes, human-machine interfaces (HCIs) are desirable which continuously monitor the users' workload and dynamically adapt the behavior of the interface to the measured workload. While memory tasks have been shown to elicit hemodynamic responses in the brain when averaging over multiple trials, a robust single trial classification is a crucial prerequisite for the purpose of dynamically adapting HCIs to the workload of its user. The prefrontal cortex (PFC) plays an important role in the processing of memory and the associated workload. In this study of 10 subjects, we used functional Near-Infrared Spectroscopy (fNIRS), a non-invasive imaging modality, to sample workload activity in the PFC. The results show up to 78% accuracy for single-trial discrimination of three levels of workload from each other. We use an n-back task (n ∈ {1, 2, 3}) to induce different levels of workload, forcing subjects to continuously remember the last one, two, or three of rapidly changing items. Our experimental results show that measuring hemodynamic responses in the PFC with fNIRS, can be used to robustly quantify and classify mental workload. Single trial analysis is still a young field that suffers from a general lack of standards. To increase comparability of fNIRS methods and results, the data corpus for this study is made available online. PMID:24474913

A clinical trial of single dose rectal and oral administration of diazepam for the prevention of serial seizures in adult epileptic patients.

PubMed Central

Milligan, N M; Dhillon, S; Griffiths, A; Oxley, J; Richens, A

1984-01-01

The clinical anticonvulsant efficacy of single dose rectal and oral administration of diazepam 20 mg was examined in two double-blind placebo-controlled trials in adult epileptic patients. All subjects suffered from drug resistant epilepsy and frequently experienced serial seizures. Diazepam was administered rectally as a new experimental suppository formulation immediately after a seizure and was highly effective in preventing recurrent fits within a 24 h observation period (p less than 0.001). Pharmacokinetic studies revealed a wide range of serum diazepam concentrations 60 min after administration of the suppository (mean serum diazepam level 190 +/- 73 (SD ng/ml). In a similar study oral administration of diazepam 20 mg significantly reduced the incidence of serial seizures compared with a placebo (p less than 0.01) and the mean 60 min serum diazepam level was 273 +/- 190 (SD) ng/ml. PMID:6368753

Conflict processing in the anterior cingulate cortex constrains response priming.

PubMed

Pastötter, Bernhard; Hanslmayr, Simon; Bäuml, Karl-Heinz T

2010-05-01

A prominent function of the anterior cingulate cortex (ACC) is to process conflict between competing response options. In this study, we investigated the role of conflict processing in a response-priming task in which manual responses were either validly or invalidly cued. Examining electrophysiological measurements of oscillatory brain activity on the source level, we found response priming to be related to a beta power decrease in the premotor cortex and conflict processing to be linked to a theta power increase in the ACC. In particular, correlation of oscillatory brain activities in the ACC and the premotor cortex showed that conflict processing reduces response priming by slowing response time in valid trials and lowering response errors in invalid trials. This relationship emerged on a between subjects level as well as within subjects, on a single trial level. These findings suggest that conflict processing in the ACC constrains the automatic priming process. 2010 Elsevier Inc. All rights reserved.

The brain’s response to pleasant touch: an EEG investigation of tactile caressing

PubMed Central

Singh, Harsimrat; Bauer, Markus; Chowanski, Wojtek; Sui, Yi; Atkinson, Douglas; Baurley, Sharon; Fry, Martin; Evans, Joe; Bianchi-Berthouze, Nadia

2014-01-01

Somatosensation as a proximal sense can have a strong impact on our attitude toward physical objects and other human beings. However, relatively little is known about how hedonic valence of touch is processed at the cortical level. Here we investigated the electrophysiological correlates of affective tactile sensation during caressing of the right forearm with pleasant and unpleasant textile fabrics. We show dissociation between more physically driven differential brain responses to the different fabrics in early somatosensory cortex – the well-known mu-suppression (10–20 Hz) – and a beta-band response (25–30 Hz) in presumably higher-order somatosensory areas in the right hemisphere that correlated well with the subjective valence of tactile caressing. Importantly, when using single trial classification techniques, beta-power significantly distinguished between pleasant and unpleasant stimulation on a single trial basis with high accuracy. Our results therefore suggest a dissociation of the sensory and affective aspects of touch in the somatosensory system and may provide features that may be used for single trial decoding of affective mental states from simple electroencephalographic measurements. PMID:25426047

Addressing standards of care in resource-limited settings.

PubMed

Dawson, Liza; Klingman, Karin L; Marrazzo, Jeanne

2014-01-01

: The choice between "best-known" standards of care (SOC) or "best available" standards as the control arm in a clinical trial is a fundamental dilemma in clinical research in resource-limited settings (RLS). When the health system is delivering less than an optimal level of care, using highest standard of care in a clinical trial may produce results that cannot be implemented or sustained locally. On the other hand, using interventions that are more feasible in the local setting may involve suboptimal care, and clinical outcomes may be affected. The need for improved standards in health systems in RLS, and the difficulty in securing them, has led many researchers advocate for policy changes at the national or international level to improve clinical care more systemically. SOC decisions in a clinical trial affect the level of benefit provided to study participants and the policy implications of the trial findings. SOC choices should provide high-quality care to help advance the health care system in host countries participating in the trial, but balancing the scientific and ethical objectives of SOC choices is difficult, and there is no single formula for selecting the appropriate SOC. Despite the challenges, well-designed and conducted clinical trials can and should make significant contributions to health systems in RLS.

Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care.

PubMed

Khunti, Kamlesh; Gray, Laura J; Skinner, Timothy; Carey, Marian E; Realf, Kathryn; Dallosso, Helen; Fisher, Harriet; Campbell, Michael; Heller, Simon; Davies, Melanie J

2012-04-26

To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years. Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level. 207 general practices in 13 primary care sites in the United Kingdom. 731 of the 824 participants included in the original trial were eligible for follow-up. Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants. A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care. The primary outcome was glycated haemoglobin (HbA(1c)) levels. The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years. HbA(1c) levels at three years had decreased in both groups. After adjusting for baseline and cluster the difference was not significant (difference -0.02, 95% confidence interval -0.22 to 0.17). The groups did not differ for the other biomedical and lifestyle outcomes and drug use. The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P<0.01). Depression scores and quality of life did not differ at three years. A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs. Current Controlled Trials ISRCTN17844016.

There's Waldo! A Normalization Model of Visual Search Predicts Single-Trial Human Fixations in an Object Search Task

PubMed Central

Miconi, Thomas; Groomes, Laura; Kreiman, Gabriel

2016-01-01

When searching for an object in a scene, how does the brain decide where to look next? Visual search theories suggest the existence of a global “priority map” that integrates bottom-up visual information with top-down, target-specific signals. We propose a mechanistic model of visual search that is consistent with recent neurophysiological evidence, can localize targets in cluttered images, and predicts single-trial behavior in a search task. This model posits that a high-level retinotopic area selective for shape features receives global, target-specific modulation and implements local normalization through divisive inhibition. The normalization step is critical to prevent highly salient bottom-up features from monopolizing attention. The resulting activity pattern constitues a priority map that tracks the correlation between local input and target features. The maximum of this priority map is selected as the locus of attention. The visual input is then spatially enhanced around the selected location, allowing object-selective visual areas to determine whether the target is present at this location. This model can localize objects both in array images and when objects are pasted in natural scenes. The model can also predict single-trial human fixations, including those in error and target-absent trials, in a search task involving complex objects. PMID:26092221

A single-blinded, single-centre, controlled study in healthy adult smokers to identify the effects of a reduced toxicant prototype cigarette on biomarkers of exposure and of biological effect versus commercial cigarettes

PubMed Central

2013-01-01

Background Despite universal acceptance that smoking is harmful, a substantial number of adults continue to smoke. The development of potential reduced exposure products (more recently termed modified risk tobacco products) has been suggested as a way to reduce the risks of tobacco smoking. This trial is designed to investigate whether changes in toxicant exposure after switching from a commercial to reduced toxicant prototype (RTP) cigarette (7 mg International Organisation for Standardisation (ISO) tar yield) can be assessed by measurement of biomarkers and other factors. The primary objective is to descriptively assess changes in selected biomarkers of exposure (BoE) and biomarkers of biological effect (BoBE) within participants and within and between groups after switching. Secondary objectives are to assess similarly changes in other biomarkers, quality of life, smoking behaviours, physiological measures, mouth-level exposure to toxicants and sensory perception. Methods/design This trial will assess current smokers, ex-smokers and never-smokers in a single-centre single-blind, controlled clinical trial with a forced-switching design and in-clinic (residential) and ambulatory (non-residential) periods. Smokers will be aged 23–55 years (minimum legal smoking age plus 5 years) and non-smokers 28–55 years (minimum legal smoking age plus 5 years, plus minimum 5 years since last smoked). Smokers will be allowed to smoke freely at all times. We will assess changes in selected BoE and BoBE and effective dose in urine and blood after switching. Creatinine concentrations in serum, creatinine clearance in urine, cotinine concentration in saliva, diaries and collection of spent cigarette filters will be used to assess compliance with the study protocol. Mouth-level exposure to toxins will be assessed by filter analysis. Discussion Data from this study are expected to improve scientific understanding of the effects of RTP cigarettes on BoE and BoBE, and give insights into study design for clinical assessment of potential MRTPs. Trial registration The study was registered in the Current Controlled Trials database under the reference ISRCTN81286286. PMID:23895296

Long-term Evaluation of Cervical Disc Arthroplasty with the Mobi-C© Cervical Disc: A Randomized, Prospective, Multicenter Clinical Trial with Seven-Year Follow-up

PubMed Central

Davis, Reginald J.; Hisey, Michael S.; Nunley, Pierce D.; Hoffman, Gregory A.; Jackson, Robert J.; Bae, Hyun W.; Albert, Todd; Coric, Dom

2017-01-01

Background Cervical total disc replacement (TDR) is an increasingly accepted procedure for the treatment of symptomatic cervical degenerative disc disease. Multiple Level I evidence clinical trials have established cervical TDR to be a safe and effective procedure in the short-term. The objective of this study is to provide a long-term assessment of TDR versus anterior discectomy and fusion for the treatment of one- and two-level disc disease. Methods This study was a continuation of a prospective, multicenter, randomized, US FDA IDE clinical trial comparing cervical TDR with the Mobi-C© Cervical Disc versus ACDF through 7 years follow-up. Inclusion criteria included a diagnosis of symptomatic cervical degenerative disc disease at one or two cervical levels. TDR patients were treated using a Mobi-C© artificial disc (Zimmer Biomet, Austin TX, USA). ACDF with allograft and anterior plate was used as a control treatment. Outcome measures were collected preoperatively and postoperatively at 6 weeks, at 3, 6, 12, 18 months, annually through 60 months, and at 84 months. Measured outcomes included Overall success, Neck Disability Index (NDI), VAS neck and arm pain, segmental range of motion (ROM), patient satisfaction, SF-12 MCS/PCS, major complications, and subsequent surgery rate. The primary endpoint was an FDA composite definition of success comprising clinical improvement and an absence of major complications and secondary surgery events. Results A total of 599 patients were enrolled and treated, with 164 treated with one-level TDR, 225 treated with two-level TDR, 81 treated with one-level ACDF, and 105 treated with two-level ACDF. At seven years, follow-up rates ranged from 73.5% to 84.4% (overall 80.2%). The overall success rates of two level TDR and ACDF patients were 60.8% and 34.2%, respectively (p<0.0001). The overall success rates of one level TDR and ACDF patients were 55.2% and 50%, respectively (p>0.05). Both the single and two level TDR and ACDF groups showed significant improvement from baseline NDI scores, VAS neck and arm pain scores, and SF-12 MCS/PCS scores (p<0.0001). In the single level cohort, there was an increased percentage of TDR patients who reported themselves as “very satisfied” (TDR 90.9% vs ACDF 77.8%; p= 0.028). There was a lower rate of adjacent level secondary surgery in the single level TDR patients (3.7%) versus the ACDF patients (13.6%; p = 0.007). In the two level TDR group, the NDI success rate was significantly greater in the TDR group (TDR: 79.0% vs. ACDF: 58.0%; p=0.001). There was significantly more improvement in NDI change score at 7 years in the TDR patients versus ACDF. The TDR group had a significantly higher rate of patients who were “very satisfied” with their treatment compared to the ACDF group (TDR: 85.9% vs. ACDF: 73.9%). The rate of subsequent surgery at the index level was significantly lower in the TDR group compared to the ACDF group (TDR: 4.4% vs. ACDF: 16.2%; p=0.001). The rate of adjacent level secondary surgery was significantly lower in the two level TDR (4.4%) patients compared to the ACDF (11.3%; p=0.03) patients. In both single and two level cohorts, the percentage of patients with worse NDI (2.5%-3.8% of two level surgeries and 1.2%-2.5% of single level surgeries) or worse neck pain (5%-6.8% of the two level surgeries and 1.3% - 3.8% of the single level surgeries) was strikingly low in both groups but trended lower in the TDR patients. Conclusions At seven years, the composite success analysis demonstrated clinical superiority of two level TDR over ACDF and non-inferiority of single level TDR versus ACDF. There were lower rates of secondary surgery and higher adjacent level disc survivorship in both groups. Both surgeries were remarkably effective in alleviating pain relative to baseline and the rate of patients with worse disability or neck pain was surprisingly low. Overall, greater than 95% of patients (from both groups) who underwent TDR and 88% of patients who underwent ACDF were “very satisfied” at seven years. The differences in clinical effectiveness of TDR versus ACDF becomes more apparent as treatment increases from one to two levels, indicating a significant benefit for TDR over ACDF for two-level procedures. Ethical Standards The Mobi-C Clinical Trial (ClinicalTrials.gov registration number: NCT00389597) was conducted at 24 sites in the US and was approved by the Institutional Review Board, Research Ethics Committee, or local equivalent of each participating site. Level of Evidence 1. PMID:29372135

A randomized clinical trial of the efficacy of single versus double-daily dose of oral iron for prevention of iron deficiency anemia in women with twin gestations.

PubMed

Ali, Mohammed K; Abbas, Ahmed M; Abdelmagied, Ahmed M; Mohammed, Ghada E; Abdalmageed, Osama S

2017-12-01

The study aims to assess the efficacy of single versus double-daily oral iron dose on prevention of iron deficiency anemia in women with twin gestations. A randomized controlled trial (NCT02858505) conducted at Woman's Health Hospital, Assiut, Egypt, between August 2015 and June 2016 included 120 non-anemic pregnant women with twin gestations in the first trimester. Women were randomly assigned to either group I (27 mg elemental iron) or group II (54 mg elemental iron) daily starting from 12 weeks of pregnancy till 36 weeks. The primary outcomes included the mean level of hemoglobin, hematocrit and serum ferritin at 36 weeks' gestation. Both iron doses maintained the mean hemoglobin and hematocrit within the normal level from 12 weeks to 36 weeks (p = 0.378 and p = 0.244, respectively). However, the mean serum ferritin level was higher in group II than group I (p = 0.000) at 36 weeks' gestation. Moreover, women in group II reported more side effects than group I at 36 weeks' gestation. Doubling the prophylactic iron dose is comparable to single dose in the prevention of iron deficiency anemia among women with twin gestations with more side effects.

Metabolic effects of propranolol and hydroflumethiazide treatment in Kenyans with mild to moderate essential hypertension.

PubMed

Yonga, G O; Ogola, E N; Orinda, D A

1993-11-01

In a prospective single-blind comparative trial, sixty newly diagnosed mild to moderate hypertensives were randomly assigned to either propranolol or hydroflumethiazide monotherapy. Baseline fasting serum glucose lipid profiles, serum uric acid and potassium levels, were determined at the beginning of the trial. Repeat levels were determined at completion of twelve weeks of treatment. Propranolol treatment significantly reduced HDL-cholesterol (p < 0.02) and increased both VLDL and total serum triglycerides (p < 0.01). Hydroflumethiazide significantly increased total and LDL-chole-sterol, fasting serum glucose and uric acid levels (p < 0.01); potassium levels were significantly lowered (p < 0.01). Treatment with either propranolol or hydroflumethiazide is associated with significant metabolic side-effects which require regular monitoring and intervention as appropriate.

Multiple imputation methods for bivariate outcomes in cluster randomised trials.

PubMed

DiazOrdaz, K; Kenward, M G; Gomes, M; Grieve, R

2016-09-10

Missing observations are common in cluster randomised trials. The problem is exacerbated when modelling bivariate outcomes jointly, as the proportion of complete cases is often considerably smaller than the proportion having either of the outcomes fully observed. Approaches taken to handling such missing data include the following: complete case analysis, single-level multiple imputation that ignores the clustering, multiple imputation with a fixed effect for each cluster and multilevel multiple imputation. We contrasted the alternative approaches to handling missing data in a cost-effectiveness analysis that uses data from a cluster randomised trial to evaluate an exercise intervention for care home residents. We then conducted a simulation study to assess the performance of these approaches on bivariate continuous outcomes, in terms of confidence interval coverage and empirical bias in the estimated treatment effects. Missing-at-random clustered data scenarios were simulated following a full-factorial design. Across all the missing data mechanisms considered, the multiple imputation methods provided estimators with negligible bias, while complete case analysis resulted in biased treatment effect estimates in scenarios where the randomised treatment arm was associated with missingness. Confidence interval coverage was generally in excess of nominal levels (up to 99.8%) following fixed-effects multiple imputation and too low following single-level multiple imputation. Multilevel multiple imputation led to coverage levels of approximately 95% throughout. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Acute effects of traditional Thai massage on cortisol levels, arterial blood pressure and stress perception in academic stress condition: A single blind randomised controlled trial.

PubMed

Bennett, Surussawadi; Bennett, Michael John; Chatchawan, Uraiwon; Jenjaiwit, Patcharaporn; Pantumethakul, Rungthip; Kunhasura, Soontorn; Eungpinichpong, Wichai

2016-04-01

Traditional Thai massage (TTM) has been applied widely to promote relaxation. However, there is little evidence to support its efficacy on academic stress. A randomised controlled trial was performed to examine the acute effects of TTM on cortisol level, blood pressure, heart rate and stress perception in academic stress. This prospective trial included 36 physiotherapy students with a self perceived stress score of between 3 and 5. They were randomly allocated into the TTM (18 people) group or the control group (18 people). Saliva cortisol level, blood pressure, heart rate and stress perception rating were measured before and after the intervention. Both groups showed a significant reduction in cortisol level and heart rate when compared with baseline (p < 0.001). There were no significant differences in cortisol level between the two groups. The results suggest the need for further study into other possible physiological effects on stress of TTM. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antennal tactile learning in the honeybee: effect of nicotinic antagonists on memory dynamics.

PubMed

Dacher, M; Lagarrigue, A; Gauthier, M

2005-01-01

Restrained worker honeybees (Apis mellifera L.) are able to learn to associate antennal-scanning of a metal plate with a sucrose reinforcement delivered to the mouthparts. Learning occurs reliably in a single association of the two sensory stimuli. The involvement of nicotinic pathways in memory formation and retrieval processes was tested by injecting, into the whole brain through the median ocellus, either mecamylamine (0.6 microg per bee) or alpha-bungarotoxin (2.4 ng per bee). Saline served as a control. Mecamylamine injected 10 min before the retrieval test impairs the retention level tested 3 h and 24 h after single- or multi-trial learning. Retrieval tests performed at various times after the injection show that the blocking effect of mecamylamine lasts about 1 h. The drug has no effect on the reconsolidation or extinction processes. Mecamylamine injected 10 min before conditioning impairs single-trial learning but has no effect on five-trial learning and on the consolidation process. By contrast, alpha-bungarotoxin only impairs the formation of long-term memory (24 h) induced by the five-trial learning and has no effect on medium-term memory (3 h), on single-trial learning or on the retrieval process. Hence, owing to previous data, at least two kinds of nicotinic receptors seem to be involved in honeybee memory, an alpha-bungarotoxin-sensitive and an alpha-bungarotoxin-insensitive receptor. Our results extend to antennal mechanosensory conditioning the role of the cholinergic system that we had previously described for olfactory conditioning in the honeybee. Moreover, we describe here in this insect a pharmacological dissociation between alpha-bungarotoxin sensitive long-term memory and alpha-bungarotoxin insensitive medium-term memory, the last one being affected by mecamylamine.

An Intelligent Man-Machine Interface—Multi-Robot Control Adapted for Task Engagement Based on Single-Trial Detectability of P300

PubMed Central

Kirchner, Elsa A.; Kim, Su K.; Tabie, Marc; Wöhrle, Hendrik; Maurus, Michael; Kirchner, Frank

2016-01-01

Advanced man-machine interfaces (MMIs) are being developed for teleoperating robots at remote and hardly accessible places. Such MMIs make use of a virtual environment and can therefore make the operator immerse him-/herself into the environment of the robot. In this paper, we present our developed MMI for multi-robot control. Our MMI can adapt to changes in task load and task engagement online. Applying our approach of embedded Brain Reading we improve user support and efficiency of interaction. The level of task engagement was inferred from the single-trial detectability of P300-related brain activity that was naturally evoked during interaction. With our approach no secondary task is needed to measure task load. It is based on research results on the single-stimulus paradigm, distribution of brain resources and its effect on the P300 event-related component. It further considers effects of the modulation caused by a delayed reaction time on the P300 component evoked by complex responses to task-relevant messages. We prove our concept using single-trial based machine learning analysis, analysis of averaged event-related potentials and behavioral analysis. As main results we show (1) a significant improvement of runtime needed to perform the interaction tasks compared to a setting in which all subjects could easily perform the tasks. We show that (2) the single-trial detectability of the event-related potential P300 can be used to measure the changes in task load and task engagement during complex interaction while also being sensitive to the level of experience of the operator and (3) can be used to adapt the MMI individually to the different needs of users without increasing total workload. Our online adaptation of the proposed MMI is based on a continuous supervision of the operator's cognitive resources by means of embedded Brain Reading. Operators with different qualifications or capabilities receive only as many tasks as they can perform to avoid mental overload as well as mental underload. PMID:27445742

The potential for improvement of outcomes by personalized insulin treatment of type 1 diabetes as assessed by analysis of single-patient data from a randomized controlled cross-over insulin trial.

PubMed

Pedersen-Bjergaard, Ulrik; Kristensen, Peter L; Beck-Nielsen, Henning; Nørgaard, Kirsten; Perrild, Hans; Christiansen, Jens S; Jensen, Tonny; Parving, Hans-Henrik; Thorsteinsson, Birger; Tarnow, Lise

2017-01-01

The evidence for optimal insulin treatment in type 1 diabetes is mainly based on randomised controlled trials applying a parallel-group design. Such trials yield robust general results but crucial individual treatment effects cannot be extracted. We aimed to assess the potential for further improvement of outcomes by personalized insulin therapy by analyzing data from a cross-over trial at individual level. Post hoc analysis of data from a two-year multicentre, prospective, randomised, open, blinded endpoint (PROBE) trial (the HypoAna trial). In a cross-over design 114 patients with type 1 diabetes and recurrent severe hypoglycemia were treated with basal-bolus therapy based on analog (detemir/aspart) or human (NPH/regular) insulin aiming at maintenance of baseline HbA1c levels. For each patient a superior outcome was defined as fewer events of severe hypoglycemia defined by need for third party treatment assistance or a more than 0.4% (4.4mmol/mol) lower HbA1c. Only one quarter had comparable outcome of the two treatments in terms of rate of severe hypoglycemia or HbA1c. Twice as many patients had superior outcome of analog-based as compared to human insulin-based insulin treatment. The rate of severe hypoglycemia with the superior treatment was lower compared to the rates obtained with analog insulin and with human insulin (0.67, 1.09, and 1.57 episode per patient-year, respectively (p<0.0001)). Personalized insulin treatment of type 1 diabetes based on single-patient evidence may improve outcomes significantly compared to a general treatment approach. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A theory-based online health behaviour intervention for new university students (U@Uni:LifeGuide): results from a repeat randomized controlled trial.

PubMed

Cameron, David; Epton, Tracy; Norman, Paul; Sheeran, Paschal; Harris, Peter R; Webb, Thomas L; Julious, Steven A; Brennan, Alan; Thomas, Chloe; Petroczi, Andrea; Naughton, Declan; Shah, Iltaf

2015-12-07

This paper reports the results of a repeat trial assessing the effectiveness of an online theory-based intervention to promote healthy lifestyle behaviours in new university students. The original trial found that the intervention reduced the number of smokers at 6-month follow-up compared with the control condition, but had non-significant effects on the other targeted health behaviours. However, the original trial suffered from low levels of engagement, which the repeat trial sought to rectify. Three weeks before staring university, all incoming undergraduate students at a large university in the UK were sent an email inviting them to participate in the study. After completing a baseline questionnaire, participants were randomly allocated to intervention or control conditions. The intervention consisted of a self-affirmation manipulation, health messages based on the theory of planned behaviour and implementation intention tasks. Participants were followed-up 1 and 6 months after starting university. The primary outcome measures were portions of fruit and vegetables consumed, physical activity levels, units of alcohol consumed and smoking status at 6-month follow-up. The study recruited 2,621 students (intervention n=1346, control n=1275), of whom 1495 completed at least one follow-up (intervention n=696, control n=799). Intention-to-treat analyses indicated that the intervention had a non-significant effect on the primary outcomes, although the effect of the intervention on fruit and vegetable intake was significant in the per-protocol analyses. Secondary analyses revealed that the intervention had significant effects on having smoked at university (self-report) and on a biochemical marker of alcohol use. Despite successfully increasing levels of engagement, the intervention did not have a significant effect on the primary outcome measures. The relatively weak effects of the intervention, found in both the original and repeat trials, may be due to the focus on multiple versus single health behaviours. Future interventions targeting the health behaviour of new university students should therefore focus on single health behaviours. Current Controlled Trials ISRCTN07407344 .

Single-case experimental design yielded an effect estimate corresponding to a randomized controlled trial.

PubMed

Shadish, William R; Rindskopf, David M; Boyajian, Jonathan G

2016-08-01

We reanalyzed data from a previous randomized crossover design that administered high or low doses of intravenous immunoglobulin (IgG) to 12 patients with hypogammaglobulinaemia over 12 time points, with crossover after time 6. The objective was to see if results corresponded when analyzed as a set of single-case experimental designs vs. as a usual randomized controlled trial (RCT). Two blinded statisticians independently analyzed results. One analyzed the RCT comparing mean outcomes of group A (high dose IgG) to group B (low dose IgG) at the usual trial end point (time 6 in this case). The other analyzed all 12 time points for the group B patients as six single-case experimental designs analyzed together in a Bayesian nonlinear framework. In the randomized trial, group A [M = 794.93; standard deviation (SD) = 90.48] had significantly higher serum IgG levels at time six than group B (M = 283.89; SD = 71.10) (t = 10.88; df = 10; P < 0.001), yielding a mean difference of MD = 511.05 [standard error (SE) = 46.98]. For the single-case experimental designs, the effect from an intrinsically nonlinear regression was also significant and comparable in size with overlapping confidence intervals: MD = 495.00, SE = 54.41, and t = 495.00/54.41 = 9.10. Subsequent exploratory analyses indicated that how trend was modeled made a difference to these conclusions. The results of single-case experimental designs accurately approximated results from an RCT, although more work is needed to understand the conditions under which this holds. Copyright © 2016 Elsevier Inc. All rights reserved.

The informational role of knowledge of results in motor learning.

PubMed

Blackwell, J R; Newell, K M

1996-07-01

An experiment is reported that was set-up to examine the informational role of knowledge of results (KR) in the learning of a single-limb movement timing task. A group with KR practiced 200 trials a day for 5 days prior to receiving a sixth day of practice without KR. The performance of this group was contrasted to another group that practiced 200 trials without KR for one day. Traditional movement error and time series analyses revealed that KR serves to calibrate the movement outcome to the task demands and modulate the performance outcome relation between trials. The degree of systematic trial-to-trial modulation was strongly dependent upon the degree of error exhibited on any given trial, and was enhanced under no-KR conditions. Information in KR has both immediate and persistent influences on learning and performance that are dependent upon the task constraints and the skill level of the performer.

Change in blood levels of eicosapentaenoic acid and posttraumatic stress symptom: A secondary analysis of data from a placebo-controlled trial of omega3 supplements.

PubMed

Matsuoka, Yutaka J; Hamazaki, Kei; Nishi, Daisuke; Hamazaki, Tomohito

2016-11-15

Eicosapentaenoic acid (EPA) is suggested to be protective against posttraumatic stress disorder (PTSD) from two observational studies. We previously conducted a randomized controlled trial and found no effect of docosahexaenoic acid (DHA) for prevention of PTSD. This secondary analysis aimed to determine whether change in blood levels of EPA is associated with PTSD symptoms. The percentages of EPA, DHA, and arachidonic acid (AA) were measured in erythrocyte membranes at baseline and posttreatment in 110 participants with severe physical injury who were randomly assigned to receive either a daily dose of 1,470mg DHA and 147mg EPA or of placebo for 12 weeks. Associations between change in erythrocyte fatty acid levels during the trial controlling for each baseline level and PTSD severity at 12 weeks were analyzed by treatment arm. In the omega3 supplements arm, changes in EPA+DHA (p=.023) and EPA (p=.001) as well as the EPA:AA ratio (p=.000) and EPA: DHA ratio (p=.013) were inversely correlated with PTSD severity. Change in AA was positively correlated with PTSD severity (p=.001). This trial was conducted at a single-center in Japan and PTSD symptoms in most participants were not serious. Increased erythrocyte level of EPA during the trial was associated with low severity of PTSD symptoms in patients receiving omega3 supplements. Copyright © 2016 Elsevier B.V. All rights reserved.

Meta-analysis of five photodisinfection clinical trials for periodontitis

NASA Astrophysics Data System (ADS)

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

2009-06-01

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

Single-trial dynamics of motor cortex and their applications to brain-machine interfaces

PubMed Central

Kao, Jonathan C.; Nuyujukian, Paul; Ryu, Stephen I.; Churchland, Mark M.; Cunningham, John P.; Shenoy, Krishna V.

2015-01-01

Increasing evidence suggests that neural population responses have their own internal drive, or dynamics, that describe how the neural population evolves through time. An important prediction of neural dynamical models is that previously observed neural activity is informative of noisy yet-to-be-observed activity on single-trials, and may thus have a denoising effect. To investigate this prediction, we built and characterized dynamical models of single-trial motor cortical activity. We find these models capture salient dynamical features of the neural population and are informative of future neural activity on single trials. To assess how neural dynamics may beneficially denoise single-trial neural activity, we incorporate neural dynamics into a brain–machine interface (BMI). In online experiments, we find that a neural dynamical BMI achieves substantially higher performance than its non-dynamical counterpart. These results provide evidence that neural dynamics beneficially inform the temporal evolution of neural activity on single trials and may directly impact the performance of BMIs. PMID:26220660

Passenger train emergency systems : single-level commuter rail car egress experiments

DOT National Transportation Integrated Search

2015-04-01

Under FRA sponsorship, a series of three experimental egress trials was conducted in 2005 and 2006 to obtain human factors data relating to the amount of time necessary for individuals to exit from a passenger rail car. This final report describes th...

Single-arm phase II trial design under parametric cure models.

PubMed

Wu, Jianrong

2015-01-01

The current practice of designing single-arm phase II survival trials is limited under the exponential model. Trial design under the exponential model may not be appropriate when a portion of patients are cured. There is no literature available for designing single-arm phase II trials under the parametric cure model. In this paper, a test statistic is proposed, and a sample size formula is derived for designing single-arm phase II trials under a class of parametric cure models. Extensive simulations showed that the proposed test and sample size formula perform very well under different scenarios. Copyright © 2015 John Wiley & Sons, Ltd.

Cost-effective treatment solutions for rural areas: design and operation of a new package treatment plant for single households.

PubMed

Daude, D; Stephenson, T

2003-01-01

The design approach and operation of a newly developed package plant treating domestic sewage from single households were evaluated. Combining submerged aerated filter (SAF) technology with jet aeration and incorporating both into a compact and shallow tank resulted in a cost-effective treatment solution. A trial unit was permanently installed at a rural site, serving a single household. Jet aeration proved to be the best aeration method for the shallow bioreactor design. Further trials revealed a 50% reduction in suspended solids (SS) through the use of a static effluent filter and found that annual plant maintenance was vital to sustain stable operating conditions. Despite high variations in influent conditions, the trial unit produced good effluent quality during steady-state operation. Average effluent BOD5, COD and SS values were 19.6 mg l(-1), 98 mg l(-1) and 32 mg l(-1) achieving overall removal efficiencies of 94.2%, 85.9% and 87.6% respectively. However, effluent ammonia nitrogen (NH4-N) levels were found to be inconsistent varying from 9 mg l(-1) to over 60 mg l(-1).

Discrimination of communication vocalizations by single neurons and groups of neurons in the auditory midbrain.

PubMed

Schneider, David M; Woolley, Sarah M N

2010-06-01

Many social animals including songbirds use communication vocalizations for individual recognition. The perception of vocalizations depends on the encoding of complex sounds by neurons in the ascending auditory system, each of which is tuned to a particular subset of acoustic features. Here, we examined how well the responses of single auditory neurons could be used to discriminate among bird songs and we compared discriminability to spectrotemporal tuning. We then used biologically realistic models of pooled neural responses to test whether the responses of groups of neurons discriminated among songs better than the responses of single neurons and whether discrimination by groups of neurons was related to spectrotemporal tuning and trial-to-trial response variability. The responses of single auditory midbrain neurons could be used to discriminate among vocalizations with a wide range of abilities, ranging from chance to 100%. The ability to discriminate among songs using single neuron responses was not correlated with spectrotemporal tuning. Pooling the responses of pairs of neurons generally led to better discrimination than the average of the two inputs and the most discriminating input. Pooling the responses of three to five single neurons continued to improve neural discrimination. The increase in discriminability was largest for groups of neurons with similar spectrotemporal tuning. Further, we found that groups of neurons with correlated spike trains achieved the largest gains in discriminability. We simulated neurons with varying levels of temporal precision and measured the discriminability of responses from single simulated neurons and groups of simulated neurons. Simulated neurons with biologically observed levels of temporal precision benefited more from pooling correlated inputs than did neurons with highly precise or imprecise spike trains. These findings suggest that pooling correlated neural responses with the levels of precision observed in the auditory midbrain increases neural discrimination of complex vocalizations.

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

PubMed Central

Fitzgerald, Kevin; White, Suellen; Borodovsky, Anna; Bettencourt, Brian R.; Strahs, Andrew; Clausen, Valerie; Wijngaard, Peter; Horton, Jay D.; Taubel, Jorg; Brooks, Ashley; Fernando, Chamikara; Kauffman, Robert S.; Kallend, David; Vaishnaw, Akshay; Simon, Amy

2018-01-01

BACKGROUND Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. METHODS In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442.) PMID:27959715

Effect of single-dose low-level helium-neon laser irradiation on orthodontic pain: a split-mouth single-blind placebo-controlled randomized clinical trial.

PubMed

Sobouti, Farhad; Khatami, Maziar; Chiniforush, Nasim; Rakhshan, Vahid; Shariati, Mahsa

2015-01-01

Pain is the most common complication of orthodontic treatment. Low-level laser therapy (LLLT) has been suggested as a new analgesic treatment free of the adverse effects of analgesic medications. However, it is not studied thoroughly, and the available studies are quite controversial. Moreover, helium neon (He-Ne) laser has not been assessed before. This split-mouth placebo-controlled randomized clinical trial was performed on 16 male and 14 female orthodontic patients requiring bilateral upper canine retraction. The study was performed at a private clinic in Sari, Iran, in 2014. It was single blind: patients, orthodontist, and personnel were blinded of the allocations, but the laser operator (periodontist) was not blinded. Once canine retractor was activated, a randomly selected maxillary quarter received a single dose of He-Ne laser irradiation (632.8 nm, 10 mw, 6 j/cm(2) density). The other quarter served as the placebo side, treated by the same device but powered off. In the first, second, fourth, and seventh days, blinded patients rated their pain sensed on each side at home using visual analog scale (VAS) questionnaires. There was no harm identified during or after the study. Pain changes were analyzed using two- and one-way repeated-measures ANOVA, Bonferroni, and t-test (α = 0.01, β > 0.99). This trial was not registered. It was self-funded by the authors. Sixteen males and 11 females remained in the study (aged 12-21). Average pain scores sensed in all 4 intervals on control and laser sides were 4.06 ± 2.85 and 2.35 ± 1.77, respectively (t-test P < 0.0001). One-way ANOVA showed significant pain declines over time, in each group (P < 0.0001). Two-way ANOVA showed significant effects for LLLT (P < 0.0001) and time (P = <0.0001). Single-dose He-Ne laser therapy might reduce orthodontic pain caused by retracting maxillary canines.

Monitoring of hormonal drug effect in a single breast cancer cell using an estrogen responsive GFP reporter vector delivered by a nanoneedle.

PubMed

Han, Sung-Woong; Nakamura, Chikashi; Imai, Yosuke; Nakamura, Noriyuki; Miyake, Jun

2009-01-01

In this study, we have evaluated a sensor system for a hormonal drug effect in a single cell level using a novel low invasive single cell DNA delivery technology using a nanoneedle. An estrogen responsive GFP reporter vector (pEREGFP9) was constructed and its estrogenic response activity was confirmed in breast cancer cells (MCF-7) using lipofection as the means of transferring the vector to the cells. The pEREGFP9 vector was delivered to a single MCF-7 using a nanoneedle and the effect of ICI 182,780, which is an antagonist of estrogen, was observed using the GFP expression level. By ICI 182,780 treatment, the fluorescence intensity of the GFP was decreased by 30-50% within 24h. This technology is the very first trial of single cell diagnosis and we are looking forward to applying it to precious single cell diagnosis in medical fields.

[Topiramate in substance-related and addictive disorders].

PubMed

Cohen, Johan; Dervaux, Alain; Laqueille, Xavier

2014-09-01

Drug treatments used in substance use disorders are not effective in all patients. To assess the effectiveness of topiramate use in the treatment of substance use disorders. Medline database from January 1966 to December 2013, Cochrane database and clinicaltrials.gov. We used keywords topiramate, addiction, substance abuse, alcohol, tobacco, nicotine, cocaine, methamphetamine, opiate, heroin, benzodiazepine, cannabis, bulimia nervosa, binge eating disorder, gambling. All clinical trials were included. Animal trials, laboratory tests, reviews, answers to writers, case-reports, case series and publications unrelated to the topic were excluded. Twenty-eight articles investigating the efficacy of topiramate in substance use were included. In alcohol-related disorder, several trials and a meta-analysis showed a reduction of days of consumption. In a single-center trial on tobacco-related disorder, topiramate was not found effective in reducing the carbon monoxide expired. In cocaine-related disorder, one single-center trial showed a reduction of days of consumption and two single-center trials have found a trend in favour of topiramate. In alcohol and cocaine co-dependency, a single-center trial found a trend in favour of topiramate. In methamphetamine-related disorder, a multicenter trial found a trend in favour of topiramate. In bulimia nervosa, two single-center trials showed a reduction in binge eating and compensatory behaviours. In binge eating disorder, several trials showed a reduction of binge eating and weight. In gambling, one single-center trial did not show any significant results. There were no randomized controlled trials found in opioid-related disorder, benzodiazepines-related disorder, and cannabis-related disorder. Definition of abstinence and methods to assess the efficacy of topiramate differed between trials. The methodological quality of included trials was variable, especially with no double-blind procedure in eight trials. Topiramate showed interest mainly in alcoholism, binge eating disorder and bulimia nervosa. No definitive conclusions can be reached for other substance use disorders such as nicotine dependence, cocaine dependence, amphetamine dependence or cannabis dependence and for gambling. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Brain-behavioral adaptability predicts response to cognitive behavioral therapy for emotional disorders: A person-centered event-related potential study.

PubMed

Stange, Jonathan P; MacNamara, Annmarie; Kennedy, Amy E; Hajcak, Greg; Phan, K Luan; Klumpp, Heide

2017-06-23

Single-trial-level analyses afford the ability to link neural indices of elaborative attention (such as the late positive potential [LPP], an event-related potential) with downstream markers of attentional processing (such as reaction time [RT]). This approach can provide useful information about individual differences in information processing, such as the ability to adapt behavior based on attentional demands ("brain-behavioral adaptability"). Anxiety and depression are associated with maladaptive information processing implicating aberrant cognition-emotion interactions, but whether brain-behavioral adaptability predicts response to psychotherapy is not known. We used a novel person-centered, trial-level analysis approach to link neural indices of stimulus processing to behavioral responses and to predict treatment outcome. Thirty-nine patients with anxiety and/or depression received 12 weeks of cognitive behavioral therapy (CBT). Prior to treatment, patients performed a speeded reaction-time task involving briefly-presented pairs of aversive and neutral pictures while electroencephalography was recorded. Multilevel modeling demonstrated that larger LPPs predicted slower responses on subsequent trials, suggesting that increased attention to the task-irrelevant nature of pictures interfered with reaction time on subsequent trials. Whereas using LPP and RT averages did not distinguish CBT responders from nonresponders, in trial-level analyses individuals who demonstrated greater ability to benefit behaviorally (i.e., faster RT) from smaller LPPs on the previous trial (greater brain-behavioral adaptability) were more likely to respond to treatment and showed greater improvements in depressive symptoms. These results highlight the utility of trial-level analyses to elucidate variability in within-subjects, brain-behavioral attentional coupling in the context of emotion processing, in predicting response to CBT for emotional disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy.

PubMed

Lin, Amy M; Rini, Brian I; Weinberg, Vivian; Fong, Kristen; Ryan, Charles J; Rosenberg, Jonathan E; Fong, Lawrence; Small, Eric J

2006-10-01

To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy. Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly. In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity. Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.

Estimating Single-Trial Responses in EEG

NASA Technical Reports Server (NTRS)

Shah, A. S.; Knuth, K. H.; Truccolo, W. A.; Mehta, A. D.; Fu, K. G.; Johnston, T. A.; Ding, M.; Bressler, S. L.; Schroeder, C. E.; Clancy, Daniel (Technical Monitor)

2002-01-01

Accurate characterization of single-trial field potential responses is critical from a number of perspectives. For example, it allows differentiation of an evoked response from ongoing EEG. We previously developed the multiple component Event Related Potential (mcERP) algorithm to improve resolution of the single-trial evoked response. The mcERP model states that multiple components, each specified by a stereotypic waveform varying in latency and amplitude from trial to trial, comprise the evoked response. Application of the mcERP algorithm to simulated data with three independent, synthetic components has shown that the model is capable of separating these components and estimating their variability. Application of the model to single trial, visual evoked potentials recorded simultaneously from all V1 laminae in an awake, fixating macaque yielded local and far-field components. Certain local components estimated by the model were distributed in both granular and supragranular laminae. This suggests a linear coupling between the responses of thalamo-recipient neuronal ensembles and subsequent responses of supragranular neuronal ensembles, as predicted by the feedforward anatomy of V1. Our results indicate that the mcERP algorithm provides a valid estimation of single-trial responses. This will enable analyses that depend on trial-to-trial variations and those that require separation of the evoked response from background EEG rhythms

Tumor response and progression-free survival as potential surrogate endpoints for overall survival in extensive stage small-cell lung cancer: findings on the basis of North Central Cancer Treatment Group trials.

PubMed

Foster, Nathan R; Qi, Yingwei; Shi, Qian; Krook, James E; Kugler, John W; Jett, James R; Molina, Julian R; Schild, Steven E; Adjei, Alex A; Mandrekar, Sumithra J

2011-03-15

The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS. Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial-level surrogacy measures included: R(2) from weighted least squares regression model, Spearman correlation coefficient, and R(2) from bivariate survival model (Copula R(2) ). Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1-10.0) and 5.5 (95% CI, 5.2-5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35-0.51; concordance index 0.63; P < .01), with 6-month PFS being the strongest (HR, 0.41; 95% CI, 0.35-0.49; concordance index, 0.66, P < .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squares R(2) = 0.79; Copula R(2) = 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squares R(2) ≤0.48). PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials. Copyright © 2010 American Cancer Society.

One-trial overshadowing: Evidence for fast specific fear learning in humans.

PubMed

Haesen, Kim; Beckers, Tom; Baeyens, Frank; Vervliet, Bram

2017-03-01

Adaptive defensive actions necessitate a fear learning system that is both fast and specific. Fast learning serves to minimize the number of threat confrontations, while specific learning ensures that the acquired fears are tied to threat-relevant cues only. In Pavlovian fear conditioning, fear acquisition is typically studied via repetitive pairings of a single cue with an aversive experience, which is not optimal for the examination of fast specific fear learning. In this study, we adopted the one-trial overshadowing procedure from basic learning research, in which a combination of two visual cues is presented once and paired with an aversive electrical stimulation. Using on-line shock expectancy ratings, skin conductance reactivity and startle reflex modulation as indices of fear learning, we found evidence of strong fear after a single conditioning trial (fast learning) as well as attenuated fear responding when only half of the trained stimulus combination was presented (specific learning). Moreover, specificity of fear responding tended to correlate with levels of state and trait anxiety. These results suggest that one-trial overshadowing can be used as a model to study fast specific fear learning in humans and individual differences therein. Copyright © 2016 Elsevier Ltd. All rights reserved.

Timing of an Adolescent Booster after Single Primary Meningococcal Serogroup C Conjugate Immunization at Young Age; An Intervention Study among Dutch Teenagers

PubMed Central

Stoof, Susanne P.; van der Klis, Fiona R. M.; van Rooijen, Debbie M.; Knol, Mirjam J.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.

2014-01-01

Background Meningococcal serogroup C (MenC) specific antibody levels decline rapidly after a single primary MenC conjugate (MenCC) vaccination in preschool children. A second MenCC vaccination during (pre)adolescence might attain longer lasting individual and herd protection. We aimed to establish an appropriate age for a (pre)adolescent MenCC booster vaccination. Methods A phase-IV trial with healthy 10-year-olds (n = 91), 12-year-olds (n = 91) and 15-year-olds (n = 86) who were primed with a MenCC vaccine nine years earlier. All participants received a booster vaccination with the same vaccine. Serum bactericidal antibody assay titers (SBA, using baby rabbit complement), MenC-polysaccharide (MenC-PS) specific IgG, IgG subclass and avidity and tetanus-specific IgG levels were measured prior to (T0) and 1 month (T1) and 1 year (T2) after the booster. An SBA titer ≥8 was the correlate of protection. Results 258 (96.3%) participants completed all three study visits. At T0, 19% of the 10-year-olds still had an SBA titer ≥8, compared to 34% of the 12-year-olds (P = 0.057) and 45% of the 15-year-olds (P<0.001). All participants developed high SBA titers (GMTs>30,000 in all age groups) and MenC-PS specific IgG levels at T1. IgG levels mainly consisted of IgG1, but the contribution of IgG2 increased with age. At T2, 100% of participants still had an SBA titer ≥8, but the 15-year-olds showed the highest protective antibody levels and the lowest decay. Conclusion Nine years after primary MenCC vaccination adolescents develop high protective antibody levels in response to a booster and are still sufficiently protected one year later. Our results suggest that persistence of individual - and herd - protection increases with the age at which an adolescent booster is administered. Trial Registration EU Clinical Trials Database 2011-000375-13 Dutch Trial Register NTR3521 PMID:24963638

Pharmacokinetics and pharmacodynamics of safinamide, a neuroprotectant with antiparkinsonian and anticonvulsant activity.

PubMed

Marzo, Antonio; Dal Bo, Lorenzo; Monti, Nunzia Ceppi; Crivelli, Fabrizio; Ismaili, Shevqet; Caccia, Carla; Cattaneo, Carlo; Fariello, Ruggero G

2004-07-01

This paper describes the pharmacokinetics and the pharmacodynamics, in terms of monoamino oxidase type B (MAO-B) inhibition, in male healthy volunteers of orally administered safinamide, a new neuroprotectant that in experimental models has demonstrated strong anticonvulsant and antiparkinson activities. Four clinical trials covering the dose range of 25-10,000 microg/kg were carried out to describe pharmacokinetics, pharmacodynamics and tolerability of safinamide, administered in single or repeated dose regimen to steady state, including a food interaction trial. All the above trials were carried out after the Ethics Committee's approval and signature of the consent form by the volunteers. In single dose trials blood sampling covered a 24 h-period in pharmacodynamic trials, 48 h-period in pharmacokinetic trials. In the case of repeated dose regimen to steady state a pre-dose sample was drawn on the first six study days, whereas the curve was explored on the 7th study day, prolonging blood sampling over a 48 h-period after the last dosing. Safinamide level was determined in plasma by a very sensitive and specific LC-MS-MS method, with a low limit of quantification of 0.5 ng/ml of plasma. Pharmacokinetic analysis was carried out with non-compartmental method and, in one case, also with the two-compartmental method. Monoamine oxidase activity of both types A and B (MAO-A and MAO-B) was determined in plasma at different times (MAO-B) and correlated to safinamide levels, or in urine (MAO-A). Pharmacokinetics of safinamide proved to be linearly and proportionally related to the administered doses. The absorption of safinamide was rapid with peak plasma concentrations ranging from 2 to 4 h. Food prolonged the rate and did not affect the extent of absorption of safinamide. In repeat dose regimen once daily, the steady state was reached on the 5th study day with a marginal accumulation factor of 1.5-1.7. The drug was cleared with a t(1/2) of about 22 h. Safinamide reversibly inhibited MAO-B enzyme. Full inhibition was observed with single doses >/= 600 microg/kg, and a relevant, dose dependent, progressive inhibition was encountered with doses starting from 25 microg/kg. Even at the highest single dose of 10 mg/kg no evidence of MAO-A inhibition was observed. Enteral absorption of the drug is linear and proportional to the doses administered. The drug is cleared from the body with a t(1/2) of approximately equal to 22 h, without producing any clinically relevant accumulation at steady state. The MAO-B inhibitory activity, without affecting MAO-A, is useful to prevent a dopamine bioinactivation in patients suffering from Parkinson's disease. Safinamide tolerability in the four clinical trials proved to be good.

Cervical spine disease may result in a negative lumbar spinal drainage trial in normal pressure hydrocephalus: case report.

PubMed

Komotar, Ricardo J; Zacharia, Brad E; Mocco, J; Kaiser, Michael G; Frucht, Stephen J; McKhann, Guy M

2008-10-01

In this case report, we present a patient with normal pressure hydrocephalus in whom a lumbar drainage trial yielded a false-negative result secondary to cervical spondylosis. An 80-year-old woman presented with classic symptoms of normal pressure hydrocephalus as well as evidence of cervical myelopathy. Magnetic resonance imaging of the brain and spine showed enlarged ventricles and single-level cervical canal narrowing. An initial lumbar drainage trial was performed, which revealed negative results. The patient then underwent cervical decompression and fusion. Despite this procedure, the patient's symptoms continued to worsen. A repeat lumbar drainage trial was performed with positive results. Subsequently, a ventriculoperitoneal shunt was placed, resulting in significant improvement of her symptoms. This case report illustrates how altered cerebrospinal fluid flow dynamics may impact the accuracy of the lumbar spinal drainage trial in patients with normal pressure hydrocephalus.

A single-blinded, single-centre, controlled study in healthy adult smokers to identify the effects of a reduced toxicant prototype cigarette on biomarkers of exposure and of biological effect versus commercial cigarettes.

PubMed

Shepperd, Christopher J; Newland, Nik; Eldridge, Alison; Graff, Don; Meyer, Ingo

2013-07-29

Despite universal acceptance that smoking is harmful, a substantial number of adults continue to smoke. The development of potential reduced exposure products (more recently termed modified risk tobacco products) has been suggested as a way to reduce the risks of tobacco smoking. This trial is designed to investigate whether changes in toxicant exposure after switching from a commercial to reduced toxicant prototype (RTP) cigarette (7 mg International Organisation for Standardisation (ISO) tar yield) can be assessed by measurement of biomarkers and other factors. The primary objective is to descriptively assess changes in selected biomarkers of exposure (BoE) and biomarkers of biological effect (BoBE) within participants and within and between groups after switching. Secondary objectives are to assess similarly changes in other biomarkers, quality of life, smoking behaviours, physiological measures, mouth-level exposure to toxicants and sensory perception. This trial will assess current smokers, ex-smokers and never-smokers in a single-centre single-blind, controlled clinical trial with a forced-switching design and in-clinic (residential) and ambulatory (non-residential) periods. Smokers will be aged 23-55 years (minimum legal smoking age plus 5 years) and non-smokers 28-55 years (minimum legal smoking age plus 5 years, plus minimum 5 years since last smoked). Smokers will be allowed to smoke freely at all times. We will assess changes in selected BoE and BoBE and effective dose in urine and blood after switching. Creatinine concentrations in serum, creatinine clearance in urine, cotinine concentration in saliva, diaries and collection of spent cigarette filters will be used to assess compliance with the study protocol. Mouth-level exposure to toxins will be assessed by filter analysis. Data from this study are expected to improve scientific understanding of the effects of RTP cigarettes on BoE and BoBE, and give insights into study design for clinical assessment of potential MRTPs. The study was registered in the Current Controlled Trials database under the reference ISRCTN81286286.

Comparison of the Effect of Sensory-Level and Conventional Motor-Level Neuromuscular Electrical Stimulations on Quadriceps Strength After Total Knee Arthroplasty: A Prospective Randomized Single-Blind Trial.

PubMed

Yoshida, Yosuke; Ikuno, Koki; Shomoto, Koji

2017-12-01

To compare sensory-level neuromuscular electrical stimulation (NMES) and conventional motor-level NMES in patients after total knee arthroplasty. Prospective randomized single-blind trial. Hospital total arthroplasty center: inpatients. Patients with osteoarthritis (N=66; mean age, 73.5±6.3y; 85% women) were randomized to receive either sensory-level NMES applied to the quadriceps (the sensory-level NMES group), motor-level NMES (the motor-level NMES group), or no stimulation (the control group) in addition to a standard rehabilitation program. Each type of NMES was applied in 45-minute sessions, 5d/wk, for 2 weeks. Data for the quadriceps maximum voluntary isometric contraction, the leg skeletal muscle mass determined using multiple-frequency bioelectrical impedance analysis, the timed Up and Go test, the 2-minute walk test, the visual analog scale, and the range of motion of the knee were measured preoperatively and at 2 and 4 weeks after total knee arthroplasty. The motor-level NMES (P=.001) and sensory-level NMES (P=.028) groups achieved better maximum voluntary isometric contraction results than did the control group. The motor-level NMES (P=.003) and sensory-level NMES (P=.046) groups achieved better 2-minute walk test results than did the control group. Some patients in the motor-level NMES group dropped out of the experiment because of discomfort. Motor-level NMES significantly improved muscle strength and functional performance more than did the standard program alone. Motor-level NMES was uncomfortable for some patients. Sensory-level NMES was comfortable and improved muscle strength and functional performance more than did the standard program alone. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Warp-averaging event-related potentials.

PubMed

Wang, K; Begleiter, H; Porjesz, B

2001-10-01

To align the repeated single trials of the event-related potential (ERP) in order to get an improved estimate of the ERP. A new implementation of the dynamic time warping is applied to compute a warp-average of the single trials. The trilinear modeling method is applied to filter the single trials prior to alignment. Alignment is based on normalized signals and their estimated derivatives. These features reduce the misalignment due to aligning the random alpha waves, explaining amplitude differences in latency differences, or the seemingly small amplitudes of some components. Simulations and applications to visually evoked potentials show significant improvement over some commonly used methods. The new implementation of the dynamic time warping can be used to align the major components (P1, N1, P2, N2, P3) of the repeated single trials. The average of the aligned single trials is an improved estimate of the ERP. This could lead to more accurate results in subsequent analysis.

Efficacy and Safety of Combined vs. Single Renin–Angiotensin–Aldosterone System Blockade in Chronic Kidney Disease: A Meta-Analysis

PubMed Central

2013-01-01

BACKGROUND Although dual blockade of the renin–angiotensin–aldosterone system (RAAS) has gained popularity for the treatment of kidney disease, its benefits and potential risks have not been fully elucidated. We conducted a meta-analysis of all randomized controlled trials comparing the efficacy and safety of combined vs. single RAAS blockade therapy in chronic kidney disease (CKD). METHODS We performed a literature search using MEDLINE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, scientific abstracts from meetings, and bibliographies of retrieved articles. We used random-effects models to compute net changes and rate differences in variables. RESULTS Fifty-nine (25 crossover and 34 parallel-arm) randomized controlled trials (RCTs) comparing the efficacy and safety of combined vs. single RAAS blockade therapy in CKD were identified (4,975 patients). Combined RAAS blockade therapy was associated with a significant net decrease in glomerular filtration rate (GFR) (–1.8ml/min or ml/min/1.73 m2; P = 0.005), albuminuria (–90mg/g of creatinine; P = 0.001 or –32mg/day; P = 0.03), and proteinuria (–291mg/g; P = 0.003 or –363mg/day; P < 0.001). Combined RAAS blockade therapy was associated with a 9.4% higher rate of regression to normoalbuminuria and a 5% higher rate of achieving the blood pressure (BP) goal (as defined in individual trials). However, combined RAAS blockade therapy was associated with a significant net increase in serum potassium level, a 3.4% higher rate of hyperkalemia, and a 4.6% higher rate of hypotension. There was no effect on doubling of the serum creatinine level, hospitalization, or mortality. CONCLUSIONS Although combined RAAS blockade therapy in CKD is associated with a decrease in albuminuria and proteinuria, it is associated with a decrease in GFR and a higher incidence of hyperkalemia and hypotension relative to monotherapy. The potential long-term kidney benefits of combined RAAS blockade therapy require further study. PMID:23382494

Pushing typists back on the learning curve: Memory chunking in the hierarchical control of skilled typewriting.

PubMed

Yamaguchi, Motonori; Logan, Gordon D

2016-12-01

Hierarchical control of skilled performance depends on the ability of higher level control to process several lower level units as a single chunk. The present study investigated the development of hierarchical control of skilled typewriting, focusing on the process of memory chunking. In the first 3 experiments, skilled typists typed words or nonwords under concurrent memory load. Memory chunks developed and consolidated into long-term memory when the same typing materials were repeated in 6 consecutive trials, but chunks did not develop when repetitions were spaced. However, when concurrent memory load was removed during training, memory chunks developed more efficiently with longer lags between repetitions than shorter lags. From these results, it is proposed that memory chunking requires 2 representations of the same letter string to be maintained simultaneously in short-term memory: 1 representation from the current trial, and the other from an earlier trial that is either retained from the immediately preceding trial or retrieved from long-term memory (i.e., study state retrieval). (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Analysis of the three United States Food and Drug Administration investigational device exemption cervical arthroplasty trials.

PubMed

Upadhyaya, Cheerag D; Wu, Jau-Ching; Trost, Gregory; Haid, Regis W; Traynelis, Vincent C; Tay, Bobby; Coric, Domagoj; Mummaneni, Praveen V

2012-03-01

There are now 3 randomized, multicenter, US FDA investigational device exemption, industry-sponsored studies comparing arthroplasty with anterior cervical discectomy and fusion (ACDF) for single-level cervical disease with 2 years of follow-up. These 3 studies evaluated the Prestige ST, Bryan, and ProDisc-C artificial discs. The authors analyzed the combined results of these trials. A total of 1213 patients with symptomatic, single-level cervical disc disease were randomized into 2 treatment arms in the 3 randomized trials. Six hundred twenty-one patients received an artificial cervical disc, and 592 patients were treated with ACDF. In the three trials, 94% of the arthroplasty group and 87% of the ACDF group have completed 2 years of follow-up. The authors analyzed the 2-year data from these 3 trials including previously unpublished source data. Statistical analysis was performed with fixed and random effects models. The authors' analysis revealed that segmental sagittal motion was preserved with arthroplasty (preoperatively 7.26° and postoperatively 8.14°) at the 2-year time point. The fusion rate for ACDF at 2 years was 95%. The Neck Disability Index, 36-Item Short Form Health Survey Mental, and Physical Component Summaries, neck pain, and arm pain scores were not statistically different between the groups at the 24-month follow-up. The arthroplasty group demonstrated superior results at 24 months in neurological success (RR 0.595, I(2) = 0%, p = 0.006). The arthroplasty group had a lower rate of secondary surgeries at the 2-year time point (RR 0.44, I(2) = 0%, p = 0.004). At the 2-year time point, the reoperation rate for adjacent-level disease was lower for the arthroplasty group when the authors analyzed the combined data set using a fixed effects model (RR 0.460, I(2) = 2.9%, p = 0.030), but this finding was not significant using a random effects model. Adverse event reporting was too heterogeneous between the 3 trials to combine for analysis. Both anterior cervical discectomy and fusion as well as arthroplasty demonstrate excellent 2-year surgical results for the treatment of 1-level cervical disc disease with radiculopathy. Arthroplasty is associated with a lower rate of secondary surgery and a higher rate of neurological success at 2 years. Arthroplasty may be associated with a lower rate of adjacent-level disease at 2 years, but further follow-up and analysis are needed to confirm this finding.

Coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone improves postprandial endothelial dysfunction in patients with borderline and stage 1 hypertension.

PubMed

Kajikawa, Masato; Maruhashi, Tatsuya; Hidaka, Takayuki; Nakano, Yukiko; Kurisu, Satoshi; Matsumoto, Takeshi; Iwamoto, Yumiko; Kishimoto, Shinji; Matsui, Shogo; Aibara, Yoshiki; Yusoff, Farina Mohamad; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Noma, Kensuke; Nakashima, Ayumu; Watanabe, Takuya; Tone, Hiroshi; Hibi, Masanobu; Osaki, Noriko; Katsuragi, Yoshihisa; Higashi, Yukihito

2018-01-12

The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for Clinical Trial: UMIN000013283.

[Rosiglitazone (BRL-49653)].

PubMed

Kameda, N; Okuya, S; Oka, Y

2000-02-01

Rosiglitazone, a thiazolidinedion antidiabetic agent, improves insulin resistance in patients with type 2 diabetes mellitus. Rosiglitazone binds to PPAR-gamma with high affinity and the in vivo antidiabetic potency of rosiglitazone is correlated with its high biding affinity. In animal models of insulin resistence, rosiglitazone decreased plasma glucose, triglyceride and insulin levels and also prevented diabetic nephropathy and pancreatic islet cell degeneration. In clinical trials in patients with type 2 diabetes mellitus, rosiglitazone, 2 to 12 mg/day (as a single daily dose or 2 divided daily doses), improved glycemic control as demonstrated, by decreases in fasting plasma glucose and HbA1C levels. Rosiglitazone did not appear to increase the risk of hypoglycemia and there was no evidence of hepatotoxicity in pre-clinical trials.

Carryover effects associated with the single-trial passive avoidance learning task in the young chick.

PubMed

Crowe, Simon F; Hale, Matthew W

2002-09-01

The single-trial passive avoidance task is a useful procedure for examining learning and memory in the young chick. However, it has recently been suggested that discrepant results reported by different laboratories are due to differences in training procedure. The present study investigated a number of parameters surrounding the passive avoidance task, using day-old White Leghorn, Black Australorp cockerels. The results suggested that presentation of a water-dipped bead immediately after the aversive bead significantly altered retention levels. In addition, when the water-dipped bead was presented after the aversive bead, chicks failed to discriminate between beads for a period of 10 min following exposure to the aversant experience. A novel variant of the passive avoidance procedure, involving pretraining with a water-dipped red bead, training with an aversant-coated red bead, and testing with a dry red bead, was evaluated. A measure of avoidance was calculated using all three trials. It is suggested that the use of a single bead, measured both before and after the training experience and using both aversant- and water-trained controls, results in the most concise characterization of memory-related phenomena in the chick which is not contaminated by a carryover effect from the aversive training experience to the nonaversive bead.

An automated and fast approach to detect single-trial visual evoked potentials with application to brain-computer interface.

PubMed

Tu, Yiheng; Hung, Yeung Sam; Hu, Li; Huang, Gan; Hu, Yong; Zhang, Zhiguo

2014-12-01

This study aims (1) to develop an automated and fast approach for detecting visual evoked potentials (VEPs) in single trials and (2) to apply the single-trial VEP detection approach in designing a real-time and high-performance brain-computer interface (BCI) system. The single-trial VEP detection approach uses common spatial pattern (CSP) as a spatial filter and wavelet filtering (WF) a temporal-spectral filter to jointly enhance the signal-to-noise ratio (SNR) of single-trial VEPs. The performance of the joint spatial-temporal-spectral filtering approach was assessed in a four-command VEP-based BCI system. The offline classification accuracy of the BCI system was significantly improved from 67.6±12.5% (raw data) to 97.3±2.1% (data filtered by CSP and WF). The proposed approach was successfully implemented in an online BCI system, where subjects could make 20 decisions in one minute with classification accuracy of 90%. The proposed single-trial detection approach is able to obtain robust and reliable VEP waveform in an automatic and fast way and it is applicable in VEP based online BCI systems. This approach provides a real-time and automated solution for single-trial detection of evoked potentials or event-related potentials (EPs/ERPs) in various paradigms, which could benefit many applications such as BCI and intraoperative monitoring. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The impact of alternate weekly collections on waste arisings.

PubMed

Williams, I D; Cole, C

2013-02-15

Residual waste is commonly collected separately from recyclable and organic materials. Different forms of collection and disposal are used internationally since regional or municipal authorities have to adapt to their own circumstances. Many authorities have adopted an alternate weekly collection (AWC) of residual waste and recyclables to force/encourage householders to recycle; however, the degree to which they achieve waste reduction has yet to be reliably quantified. This study reports on how the introduction of AWCs affects household waste arisings. The paper evaluates single and dual stream collection methods and compares their performance with the previous system. Household waste collection trials were conducted between March and June 2009 in England (Lichfield). The trials examined changes to frequency of collection, type of container issued, amounts of sorting required of residents, household participation and productivity levels. A survey of households was completed before any changes were implemented. The quantity of recyclates collected was examined for 2008/2009 and 2009/2010. The study showed that the AWC scheme positively impacted on recycling rates and household behaviour, with no adverse impacts on public participation, household waste arisings or the local environment. No public health problems were reported. Both trials saw an increase in the quantities of recyclates collected per household during the trial period compared to the same period of time in the previous year. The dual stream performed better than the single stream, collecting an average of 5.94 kg/hh/week compared to an average of 5.63 kg/hh/week. The single stream system showed a greater increase in the weight of material collected (0.53 kg/hh/week vs. 0.48 kg/hh/week). Participation and set-out rates showed an increase during the trial period. The single stream option (comingled materials in one container) outperformed the dual stream service. The reduction in costs and improved productivity were the principal reasons used for extending the trial and making changes to the district's waste collections. The study clearly demonstrates the benefits of local authorities and universities collaborating and identifies practical logistical and operational issues that need to be anticipated. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2018-01-01

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. Key points Single-leg balance demonstrated acceptable inter-trial and inter-test reliability. Single-leg landing demonstrated good inter-trial and inter-test reliability for measures of relative peak landing force and relative impulse, but not time to stabilization. Of the variables investigated, sway velocity and relative landing impulse are the most reliable measures of single-leg balance and landing respectively, and should considered for monitoring changes in postural control. PMID:29769817

Post-Learning Arousal Change and Long-Term Retention.

ERIC Educational Resources Information Center

Kumar, V.K.; Farley, Frank H.

This study examined the effects on long-term retention of variations in intensity and of temporal parameters of arousal following a single learning trial in a paired-associate task. The subjects were 56 female university students. Intensity of arousal was manipulated by using two levels of white noise--75 decibels and 90 decibels sound pressure…

The effect of high total ammonia concentration on the survival of channel catfish experimentally infected with Flavobacterium columnare

USDA-ARS?s Scientific Manuscript database

Although it is generally accepted that elevated ammonia levels in the water increase mortalities of Flavobacterium columnare infected fish, recent observation at our laboratory indicated otherwise. Two trials were conducted to determine the effect of a single immersion flush treatment of total ammo...

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial.

PubMed

Bluth, T; Teichmann, R; Kiss, T; Bobek, I; Canet, J; Cinnella, G; De Baerdemaeker, L; Gregoretti, C; Hedenstierna, G; Hemmes, S N; Hiesmayr, M; Hollmann, M W; Jaber, S; Laffey, J G; Licker, M J; Markstaller, K; Matot, I; Müller, G; Mills, G H; Mulier, J P; Putensen, C; Rossaint, R; Schmitt, J; Senturk, M; Serpa Neto, A; Severgnini, P; Sprung, J; Vidal Melo, M F; Wrigge, H; Schultz, M J; Pelosi, P; Gama de Abreu, M

2017-04-28

Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m 2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH 2 O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH 2 O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016.

Initiating change locally in bullying and aggression through the school environment (INCLUSIVE) trial: update to cluster randomised controlled trial protocol.

PubMed

Bonell, Chris; Mathiot, Anne; Allen, Elizabeth; Bevilacqua, Leonardo; Christie, Deborah; Elbourne, Diana; Fletcher, Adam; Grieve, Richard; Legood, Rosa; Scott, Stephen; Warren, Emily; Wiggins, Meg; Viner, Russell M

2017-05-25

Systematic reviews suggest that multi-component interventions are effective in reducing bullying victimisation and perpetration. We are undertaking a phase III randomised trial of the INCLUSIVE multi-component intervention. This trial aims to assess the effectiveness and cost-effectiveness of the INCLUSIVE intervention in reducing aggression and bullying victimisation in English secondary schools. This paper updates the original trial protocol published in 2014 (Trials 15:381, 2014) and presents the changes in the process evaluation protocol and the secondary outcome data collection. The methods are summarised as follows. cluster randomised trial. 40 state secondary schools. Outcomes assessed among the cohort of students at the end of year 7 (n = 6667) at baseline. INCLUSIVE is a multi-component school intervention including a social and emotional learning curriculum, changes to school environment (an action group comprising staff and students reviews local data on needs to review rules and policies and determine other local actions) and staff training in restorative practice. The intervention will be delivered by schools supported in the first two years by educational facilitators independent of the research team, with a third intervention year involving no external facilitation but all other elements. Comparator: normal practice. Primary: Two primary outcomes at student level assessed at baseline and at 36 months: 1. Aggressive behaviours in school: Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale (ESYTC) 2. Bullying and victimisation: Gatehouse Bullying Scale (GBS) Secondary outcomes assessed at baseline, 24 and 36 months will include measures relating to the economic evaluation, psychosocial outcomes in students and staff and school-level truancy and exclusion rates. 20 schools per arm will provide 90% power to identify an effect size of 0.25 SD with a 5% significance level. Randomisation: eligible consenting schools were randomised stratified for single-sex versus mixed-sex schools, school-level deprivation and measures of school attainment. The trial involves independent research and intervention teams and is supervised by a Trial Steering Committee and a Data Monitoring Committee. Current Controlled Trials, ISRCTN10751359 . Registered on 11 March 2014.

Effects of age on cognitive control during semantic categorization.

PubMed

Mudar, Raksha A; Chiang, Hsueh-Sheng; Maguire, Mandy J; Spence, Jeffrey S; Eroh, Justin; Kraut, Michael A; Hart, John

2015-01-01

We used event-related potentials (ERPs) to study age effects of perceptual (basic-level) vs. perceptual-semantic (superordinate-level) categorization on cognitive control using the go/nogo paradigm. Twenty-two younger (11 M; 21 ± 2.2 years) and 22 older adults (9 M; 63 ± 5.8 years) completed two visual go/nogo tasks. In the single-car task (SiC) (basic), go/nogo responses were made based on single exemplars of a car (go) and a dog (nogo). In the object animal task (ObA) (superordinate), responses were based on multiple exemplars of objects (go) and animals (nogo). Each task consisted of 200 trials: 160 (80%) 'go' trials that required a response through button pressing and 40 (20%) 'nogo' trials that required inhibition/withholding of a response. ERP data revealed significantly reduced nogo-N2 and nogo-P3 amplitudes in older compared to younger adults, whereas go-N2 and go-P3 amplitudes were comparable in both groups during both categorization tasks. Although the effects of categorization levels on behavioral data and P3 measures were similar in both groups with longer response times, lower accuracy scores, longer P3 latencies, and lower P3 amplitudes in ObA compared to SiC, N2 latency revealed age group differences moderated by the task. Older adults had longer N2 latency for ObA compared to SiC, in contrast, younger adults showed no N2 latency difference between SiC and ObA. Overall, these findings suggest that age differentially affects neural processing related to cognitive control during semantic categorization. Furthermore, in older adults, unlike in younger adults, levels of categorization modulate neural processing related to cognitive control even at the early stages (N2). Published by Elsevier B.V.

Is dibotermin alfa a cost-effective substitute for autologous iliac crest bone graft in single level lumbar interbody spine fusion?

PubMed

Svedbom, Axel; Paech, Daniel; Leonard, Catherine; Donnell, David; Song, Fujian; Boszcyk, Bronek; Rothenfluh, Dominique A; Lloyd, Andrew; Borgman, Benny

2015-11-01

To evaluate the cost-effectiveness of dibotermin alfa compared with autologous iliac crest bone graft (ICBG) for patients undergoing single level lumbar interbody spinal fusion in a UK hospital setting. An individual patient data (IPD) meta-analysis of six randomized controlled clinical trials and two single arm trials compared dibotermin alfa on an absorbable collagen implantation matrix (ACIM) (n = 456) and ICBG (n = 244) on resource use, re-operation rates, and SF-6D (Short form 6-dimension) health utility (total N = 700). Failure-related second surgery, operating time, post-operative hospital stay, and quality-adjusted life years (QALYs) derived from the IPD meta-analysis were included as inputs in an economic evaluation undertaken to assess the cost-effectiveness of dibotermin alfa/ACIM versus ICBG for patients undergoing single level lumbar interbody spinal fusion. A four year time horizon and the United Kingdom (UK) National Health Service (NHS) and Personal Social Services (PSS) perspective was adopted in the base case, with sensitivity analyses performed to gauge parameter uncertainty. In the base case analysis, patients treated using dibotermin alfa/ACIM (12 mg pack) accrued 0.055 incremental QALYs at an incremental cost of £ 737, compared with patients treated with ICBG. This resulted in an incremental cost-effectiveness ratio (ICER) of £ 13,523, indicating that at a willingness-to-pay threshold of £ 20,000, dibotermin alfa/ACIM is a cost-effective intervention relative to ICBG from the NHS and PSS perspective. In a UK hospital setting, dibotermin alfa/ACIM is a cost-effective substitute for ICBG for patients who require lumbar interbody arthrodesis.

Meta-analyses and adaptive group sequential designs in the clinical development process.

PubMed

Jennison, Christopher; Turnbull, Bruce W

2005-01-01

The clinical development process can be viewed as a succession of trials, possibly overlapping in calendar time. The design of each trial may be influenced by results from previous studies and other currently proceeding trials, as well as by external information. Results from all of these trials must be considered together in order to assess the efficacy and safety of the proposed new treatment. Meta-analysis techniques provide a formal way of combining the information. We examine how such methods can be used in combining results from: (1) a collection of separate studies, (2) a sequence of studies in an organized development program, and (3) stages within a single study using a (possibly adaptive) group sequential design. We present two examples. The first example concerns the combining of results from a Phase IIb trial using several dose levels or treatment arms with those of the Phase III trial comparing the treatment selected in Phase IIb against a control This enables a "seamless transition" from Phase IIb to Phase III. The second example examines the use of combination tests to analyze data from an adaptive group sequential trial.

Preventing falls in older multifocal glasses wearers by providing single-lens distance glasses: the protocol for the VISIBLE randomised controlled trial

PubMed Central

Haran, Mark J; Lord, Stephen R; Cameron, Ian D; Ivers, Rebecca Q; Simpson, Judy M; Lee, Bonsan B; Porwal, Mamta; Kwan, Marcella MS; Severino, Connie

2009-01-01

Background Recent research has shown that wearing multifocal glasses increases the risk of trips and falls in older people. The aim of this study is to determine whether the provision of single-lens distance glasses to older multifocal glasses wearers, with recommendations for wearing them for walking and outdoor activities, can prevent falls. We will also measure the effect of the intervention on health status, lifestyle activities and fear of falling, as well as the extent of adherence to the program. Methods/Design Approximately 580 older people who are regular wearers of multifocal glasses people will be recruited. Participants will be randomly allocated to either an intervention group (provision of single lens glasses, with counselling and advice about appropriate use) or a control group (usual care). The primary outcome measure will be falls (measured with 13 monthly calendars). Secondary measures will be quality of life, falls efficacy, physical activity levels and adverse events. Discussions The study will determine the impact of providing single-lens glasses, with advice about appropriate use, on preventing falls in older regular wearers of multifocal glasses. This pragmatic intervention, if found to be effective, will guide practitioners with regard to recommending appropriate glasses for minimising the risk of falls in older people. Trial Registration The protocol for this study was registered with the Clinical Trials.gov Protocol Registration System on June 7th 2006 (#350855). PMID:19321012

Intradiskal methylene blue treatment for diskogenic low back pain.

PubMed

Levi, David S; Horn, Scott; Walko, Edward

2014-11-01

Low back pain is a leading cause of pain and disability. The intervertebral disk has been identified as the most common source of chronic low back pain. Although prior treatments directed at intervertebral disks have been disappointing, recent studies show promising improvement of pain and function after a single intradiskal injection of methylene blue. To assess changes in pain and function in patients with diskogenic low back pain, diagnosed by diskography, after an intradiskal injection of methylene blue. Prospective trial. Patients diagnosed with diskogenic pain by diskography underwent a single treatment of intradiskal injection of methylene blue, determined by prior provocation diskography. Pain and function measurements were completed at baseline and 1, 2, and 6 months after treatment. Treatment was considered a categorical success based on a 30% improvement in pain according to a visual analog scale (VAS) and function on the Oswestry Disability Index (ODI). Treatment was considered a categorical failure if less than 30% improvement in pain and function was achieved or if the patient pursued other invasive treatment options during the trial period. Sixteen patients received the intradiskal methylene blue injection. Eleven patients received a single-level injection, 4 patients received a 2-level injection, and one patient received injections at 3 levels. For the VAS, at 1, 2, and 6 months after the injection, the categorical success rates were 25%, 21%, and 25%, respectively. For the ODI, at 1, 2 and 6 months after the injection, the categorical success rates were 25%, 21%, and 33%, respectively. The overall categorical success rates at 1, 2, and 6 months after the injection were 19%, 21%, and 25%, respectively. This small trial did not demonstrate overall clinical success of intradiskal methylene blue injection for patients diagnosed with diskogenic pain by diskography. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework

PubMed Central

Jull, J; Whitehead, M; Petticrew, M; Kristjansson, E; Gough, D; Petkovic, J; Volmink, J; Weijer, C; Taljaard, M; Edwards, S; Mbuagbaw, L; Cookson, R; McGowan, J; Lyddiatt, A; Boyer, Y; Cuervo, L G; Armstrong, R; White, H; Yoganathan, M; Pantoja, T; Shea, B; Pottie, K; Norheim, O; Baird, S; Robberstad, B; Sommerfelt, H; Asada, Y; Wells, G; Tugwell, P; Welch, V

2017-01-01

Background Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. Methods An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. Results A randomised trial can usefully be classified as ‘health equity relevant’ if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as ‘health equity relevant’ may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. Conclusion The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity. PMID:28951402

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

PubMed

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

2018-06-29

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

Single trial prediction of self-paced reaching directions from EEG signals.

PubMed

Lew, Eileen Y L; Chavarriaga, Ricardo; Silvoni, Stefano; Millán, José Del R

2014-01-01

Early detection of movement intention could possibly minimize the delays in the activation of neuroprosthetic devices. As yet, single trial analysis using non-invasive approaches for understanding such movement preparation remains a challenging task. We studied the feasibility of predicting movement directions in self-paced upper limb center-out reaching tasks, i.e., spontaneous movements executed without an external cue that can better reflect natural motor behavior in humans. We reported results of non-invasive electroencephalography (EEG) recorded from mild stroke patients and able-bodied participants. Previous studies have shown that low frequency EEG oscillations are modulated by the intent to move and therefore, can be decoded prior to the movement execution. Motivated by these results, we investigated whether slow cortical potentials (SCPs) preceding movement onset can be used to classify reaching directions and evaluated the performance using 5-fold cross-validation. For able-bodied subjects, we obtained an average decoding accuracy of 76% (chance level of 25%) at 62.5 ms before onset using the amplitude of on-going SCPs with above chance level performances between 875 to 437.5 ms prior to onset. The decoding accuracy for the stroke patients was on average 47% with their paretic arms. Comparison of the decoding accuracy across different frequency ranges (i.e., SCPs, delta, theta, alpha, and gamma) yielded the best accuracy using SCPs filtered between 0.1 to 1 Hz. Across all the subjects, including stroke subjects, the best selected features were obtained mostly from the fronto-parietal regions, hence consistent with previous neurophysiological studies on arm reaching tasks. In summary, we concluded that SCPs allow the possibility of single trial decoding of reaching directions at least 312.5 ms before onset of reach.

Minimizing Adverse Events While Maintaining Clinical Improvement in a Pediatric Attention-Deficit/Hyperactivity Disorder Crossover Trial with Dextroamphetamine and Methylphenidate

PubMed Central

Aabech, Henning S.; Sundet, Kjetil

2014-01-01

Abstract Objective: The purpose of this study was to investigate whether the availability of both dextroamphetamine and methylphenidate provides an opportunity to minimize adverse events in a pediatric attention-deficit/hyperactivity disorder (ADHD) stimulant trial. Methods: Thirty-six medication-naïve children 9–14 years of age, diagnosed with ADHD, were enrolled for 6 weeks in a crossover trial, with 2 weeks of methylphenidate, dextroamphetamine, and a placebo in a randomly assigned, counterbalanced sequence. Barkley's Side-Effect Rating Scale (SERS), rated by parents, was used to assess adverse events. SERS were available for 34 children, and data were analyzed both at the group and the single-subject level. Results: The side-effect profiles of dextroamphetamine and methylphenidate appeared similar at the group level. Overall, insomnia and decreased appetite were the only adverse events associated with the stimulants as compared with placebo. No significant increase from placebo to stimulant conditions was detected on SERS items reflecting emotional symptoms. Furthermore, dextroamphetamine and methylphenidate did not differ from each other on any SERS item, except that dextroamphetamine was associated with higher severity of “insomnia” and a higher prevalence of “unusually happy.” Single-subject analyses showed that one or more adverse events were reported in 14 children (41%), and were evenly distributed between those with dextroamphetamine as the drug that showed the greatest reduction in their ADHD symptoms (“best drug”) and those with methylphenidate as their best drug. Among children in whom both stimulants were associated with a decrease in ADHD symptoms, a clinically valid difference between the two stimulants in total adverse events score was found in 7 (39%) of the 18 cases. In these children, the availability of both stimulants provided an opportunity to minimize adverse events, while maintaining a reduction in ADHD symptoms. Conclusions: The availability of both dextroamphetamine and methylphenidate may contribute to minimize adverse events in a subsample of children in pediatric ADHD stimulant trials. Clinical Trials Registry: The study was first registered in clinical trials September 28, 2010. Clinical Trials.gov Identifier: NCT01220440. PMID:24666268

European Marketing Authorizations Granted Based on a Single Pivotal Clinical Trial: The Rule or the Exception?

PubMed

Morant, Anne Vinther; Vestergaard, Henrik Tang

2018-07-01

A minimum of two positive, adequate, and well-controlled clinical trials has historically been the gold standard for providing substantial evidence to support regulatory approval of a new medicine. Nevertheless, the present analysis of European Marketing Authorizations granted between 2012 and 2016 showed that 45% of new active substances were approved based on a single pivotal clinical trial. For therapeutic areas such as oncology and cardiovascular diseases, approvals based on a single pivotal trial are the rule rather than the exception, whereas new medicines within the nervous system area were generally supported by two or more pivotal trials. While overall similar trends have been observed in the US, the recent US Food and Drug Administration approvals of nervous system medicines based on a single pivotal trial suggest that a case-by-case scientific evaluation of the totality of evidence is increasingly applied to facilitate faster access of new medicines to patients suffering from serious diseases. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Acute effects of single and multiple level thoracic manipulations on chronic mechanical neck pain: a randomized controlled trial

PubMed Central

Puntumetakul, Rungthip; Suvarnnato, Thavatchai; Werasirirat, Phurichaya; Uthaikhup, Sureeporn; Yamauchi, Junichiro; Boucaut, Rose

2015-01-01

Background Thoracic spine manipulation has become a popular alternative to local cervical manipulative therapy for mechanical neck pain. This study investigated the acute effects of single-level and multiple-level thoracic manipulations on chronic mechanical neck pain (CMNP). Methods Forty-eight patients with CMNP were randomly allocated to single-level thoracic manipulation (STM) at T6–T7 or multiple-level thoracic manipulation (MTM), or to a control group (prone lying). Cervical range of motion (CROM), visual analog scale (VAS), and the Thai version of the Neck Disability Index (NDI-TH) scores were measured at baseline, and at 24-hour and at 1-week follow-up. Results At 24-hour and 1-week follow-up, neck disability and pain levels were significantly (P<0.05) improved in the STM and MTM groups compared with the control group. CROM in flexion and left lateral flexion were increased significantly (P<0.05) in the STM group when compared with the control group at 1-week follow-up. The CROM in right rotation was increased significantly after MTM compared to the control group (P<0.05) at 24-hour follow-up. There were no statistically significant differences in neck disability, pain level at rest, and CROM between the STM and MTM groups. Conclusion These results suggest that both single-level and multiple-level thoracic manipulation improve neck disability, pain levels, and CROM at 24-hour and 1-week follow-up in patients with CMNP. PMID:25624764

Intrarater and interrater reliability of assessment of lumbar multifidus muscle thickness using rehabilitative ultrasound imaging.

PubMed

Wallwork, Tracy L; Hides, Julie A; Stanton, Warren R

2007-10-01

Within-session intrarater and interrater reliability study. To establish the intrarater and interrater reliability of thickness measurements of the multifidus muscle in a parasagittal plane, conducted by an experienced ultrasound operator and a novice assessor. There is considerable evidence for the important role of the multifidus muscle in segmental stabilization of the lumbar spine. The cross-sectional area of the multifidus muscle has been assessed in healthy subjects and patients with low back pain using real-time ultrasound imaging. However, few studies have measured the thickness of the multifidus muscle using a parasagittal view. The thickness of the multifidus muscle was measured at rest, using real-time ultrasound imaging, in 10 subjects without a history of low back pain, at the levels of the L2-3 and L4-5 zygapophyseal joints. The measure was carried out 3 times at each level by 2 assessors (1 experienced, 1 novice). Intrarater (model 3) and interrater (model 2) reliability was assessed by calculation of an F statistic (analysis of variance), the intraclass correlation coefficient (ICC), and the standard error of measurement (SEM). On the basis of an average of 3 trials, the 2 operators showed very high interrater agreement on the measurement of thicknesses at the L2-3 level (ICC2,3 = 0.96; 95% CI: 0.84 to 0.99) and the L4-5 vertebral level (ICC2,3 = 0.97; 95% CI: 0.87 to 0.99), with no systematic differences in muscle size across operators (P > .05). Interrater reliability was relatively lower for the L2-3 level (ICC2,1 = 0.85; 95% CI: 0.51 to 0.96) than the L4-5 level (ICC2,1 = 0.87; 95% CI: 0.52 to 0.97) when a single trial per rater was used, but these values still indicated a high level of agreement. In addition, the novice and experienced operator produced reliable intrarater measurements at L2-3 (ICC3,1 = 0.89; 95% CI: 0.72 to 0.97 and 0.94; 95% CI: 0.86 to 0.99) and at L4-5 (ICC3,1 = 0.88; 95% CI: 0.68 to 0.97 and 0.95; 95% CI: 0.86 to 0.99), with no systematic differences in muscle size across trials (P > .05). The consistently low SEM values also indicate low measurement error. A novice and an experienced assessor were both able to reliably perform this measure at rest for 2 vertebral levels using real-time ultrasound imaging. An average of 3 trials produced higher interrater reliability scores, though using a single trial per rater was also reliable.

Existing data sources for clinical epidemiology: Aarhus University Clinical Trial Candidate Database, Denmark.

PubMed

Nørrelund, Helene; Mazin, Wiktor; Pedersen, Lars

2014-01-01

Denmark is facing a reduction in clinical trial activity as the pharmaceutical industry has moved trials to low-cost emerging economies. Competitiveness in industry-sponsored clinical research depends on speed, quality, and cost. Because Denmark is widely recognized as a region that generates high quality data, an enhanced ability to attract future trials could be achieved if speed can be improved by taking advantage of the comprehensive national and regional registries. A "single point-of-entry" system has been established to support collaboration between hospitals and industry. When assisting industry in early-stage feasibility assessments, potential trial participants are identified by use of registries to shorten the clinical trial startup times. The Aarhus University Clinical Trial Candidate Database consists of encrypted data from the Danish National Registry of Patients allowing an immediate estimation of the number of patients with a specific discharge diagnosis in each hospital department or outpatient specialist clinic in the Central Denmark Region. The free access to health care, thorough monitoring of patients who are in contact with the health service, completeness of registration at the hospital level, and ability to link all databases are competitive advantages in an increasingly complex clinical trial environment.

Tilmicosin as a single injection treatment for respiratory disease of feedlot cattle

PubMed Central

Gorham, Paul E.; Carroll, Lamar H.; McAskill, Jack W.; Watkins, Lee E.; Ose, Earl E.; Tonkinson, Lealon V.; Merrill, John K.

1990-01-01

Tilmicosin, a new semi-synthetic macrolide antibiotic, was evaluated in eight field trials as a single subcutaneous injection at dosages of 0 (placebo), 5, 10 and 20 mg/kg for the treatment of naturally occurring respiratory disease in feedlot cattle. Animals for these trials were selected from large groups of recently-shipped feeder cattle at the time clinical signs of respiratory disease and body temperature of 40.6°C or higher were observed. Treated animals were evaluated daily for 10 days and finally at day 28. Each animal was weighed on the first day and again on day 28. Animals that died were necropsied. All treatment dosages were effective in significantly lowering mortality, improving weight gains, lowering body temperature, and reducing the severity of clinical signs when compared to the placebo-treated controls. Body temperature was the only variable with statistically significant differences among the dose levels. PMID:17423706

Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

PubMed

Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand

2014-05-01

In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

Group-Level EEG-Processing Pipeline for Flexible Single Trial-Based Analyses Including Linear Mixed Models.

PubMed

Frömer, Romy; Maier, Martin; Abdel Rahman, Rasha

2018-01-01

Here we present an application of an EEG processing pipeline customizing EEGLAB and FieldTrip functions, specifically optimized to flexibly analyze EEG data based on single trial information. The key component of our approach is to create a comprehensive 3-D EEG data structure including all trials and all participants maintaining the original order of recording. This allows straightforward access to subsets of the data based on any information available in a behavioral data structure matched with the EEG data (experimental conditions, but also performance indicators, such accuracy or RTs of single trials). In the present study we exploit this structure to compute linear mixed models (LMMs, using lmer in R) including random intercepts and slopes for items. This information can easily be read out from the matched behavioral data, whereas it might not be accessible in traditional ERP approaches without substantial effort. We further provide easily adaptable scripts for performing cluster-based permutation tests (as implemented in FieldTrip), as a more robust alternative to traditional omnibus ANOVAs. Our approach is particularly advantageous for data with parametric within-subject covariates (e.g., performance) and/or multiple complex stimuli (such as words, faces or objects) that vary in features affecting cognitive processes and ERPs (such as word frequency, salience or familiarity), which are sometimes hard to control experimentally or might themselves constitute variables of interest. The present dataset was recorded from 40 participants who performed a visual search task on previously unfamiliar objects, presented either visually intact or blurred. MATLAB as well as R scripts are provided that can be adapted to different datasets.

On the Agreement between Manual and Automated Methods for Single-Trial Detection and Estimation of Features from Event-Related Potentials

PubMed Central

Biurrun Manresa, José A.; Arguissain, Federico G.; Medina Redondo, David E.; Mørch, Carsten D.; Andersen, Ole K.

2015-01-01

The agreement between humans and algorithms on whether an event-related potential (ERP) is present or not and the level of variation in the estimated values of its relevant features are largely unknown. Thus, the aim of this study was to determine the categorical and quantitative agreement between manual and automated methods for single-trial detection and estimation of ERP features. To this end, ERPs were elicited in sixteen healthy volunteers using electrical stimulation at graded intensities below and above the nociceptive withdrawal reflex threshold. Presence/absence of an ERP peak (categorical outcome) and its amplitude and latency (quantitative outcome) in each single-trial were evaluated independently by two human observers and two automated algorithms taken from existing literature. Categorical agreement was assessed using percentage positive and negative agreement and Cohen’s κ, whereas quantitative agreement was evaluated using Bland-Altman analysis and the coefficient of variation. Typical values for the categorical agreement between manual and automated methods were derived, as well as reference values for the average and maximum differences that can be expected if one method is used instead of the others. Results showed that the human observers presented the highest categorical and quantitative agreement, and there were significantly large differences between detection and estimation of quantitative features among methods. In conclusion, substantial care should be taken in the selection of the detection/estimation approach, since factors like stimulation intensity and expected number of trials with/without response can play a significant role in the outcome of a study. PMID:26258532

Prediction of successful memory encoding based on single-trial rhinal and hippocampal phase information.

PubMed

Höhne, Marlene; Jahanbekam, Amirhossein; Bauckhage, Christian; Axmacher, Nikolai; Fell, Juergen

2016-10-01

Mediotemporal EEG characteristics are closely related to long-term memory formation. It has been reported that rhinal and hippocampal EEG measures reflecting the stability of phases across trials are better suited to distinguish subsequently remembered from forgotten trials than event-related potentials or amplitude-based measures. Theoretical models suggest that the phase of EEG oscillations reflects neural excitability and influences cellular plasticity. However, while previous studies have shown that the stability of phase values across trials is indeed a relevant predictor of subsequent memory performance, the effect of absolute single-trial phase values has been little explored. Here, we reanalyzed intracranial EEG recordings from the mediotemporal lobe of 27 epilepsy patients performing a continuous word recognition paradigm. Two-class classification using a support vector machine was performed to predict subsequently remembered vs. forgotten trials based on individually selected frequencies and time points. We demonstrate that it is possible to successfully predict single-trial memory formation in the majority of patients (23 out of 27) based on only three single-trial phase values given by a rhinal phase, a hippocampal phase, and a rhinal-hippocampal phase difference. Overall classification accuracy across all subjects was 69.2% choosing frequencies from the range between 0.5 and 50Hz and time points from the interval between -0.5s and 2s. For 19 patients, above chance prediction of subsequent memory was possible even when choosing only time points from the prestimulus interval (overall accuracy: 65.2%). Furthermore, prediction accuracies based on single-trial phase surpassed those based on single-trial power. Our results confirm the functional relevance of mediotemporal EEG phase for long-term memory operations and suggest that phase information may be utilized for memory enhancement applications based on deep brain stimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of Safety and Effectiveness of the Extracorporeal Continuous-Flow Ventricular Assist Device (BR16010) Use as a Bridge-to-Decision Therapy for Severe Heart Failure or Refractory Cardiogenic Shock: Study Protocol for Single-Arm Non-randomized, Uncontrolled, and Investigator-Initiated Clinical Trial.

PubMed

Fukushima, Norihide; Tatsumi, Eisuke; Seguchi, Osamu; Takewa, Yoshiaki; Hamasaki, Toshimitsu; Onda, Kaori; Yamamoto, Haruko; Hayashi, Teruyuki; Fujita, Tomoyuki; Kobayashi, Junjiro

2018-06-08

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. The purpose of this study (NCVC-BTD_01, National Cerebral and Cardiovascular Center-Bridge to Dicision_01) is to assess the safety and effectiveness of the newly developed extracorporeal continuous-flow ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing (BR16010) use as a bridge-to-decision therapy for patients with severe heart failure or refractory cardiogenic shock. NCVC-BTD_01 is a single-center, single-arm, open-label, exploratory, medical device, investigator-initiated clinical study. It is conducted at the National Cerebral and Cardiovascular Center in Japan. A total of nine patients will be enrolled in the study. The study was planned using Simon's minimax two-stage phase design. The primary endpoint is a composite of survival free of device-related serious adverse events and complications during device support. For left ventricular assistance, withdrawal of a trial device due to cardiac function recovery or exchange to other ventricular assist devices (VADs) for the purpose of bridge to transplantation (BTT) during 30 days after implantation will be considered study successes. For right ventricular assistance, withdrawal of tal device due to right ventricular function recovery within 30 days after implantation will be considered a study success. Secondary objectives include changes in brain natriuretic peptide levels (7 days after implantation of a trial device and the day of withdrawal of a trial device), period of mechanical ventricular support, changes in left ventricular ejection fraction (7 days after implantation of a trial device and the day of withdrawal of a trial device), and changes in left ventricular diastolic dimension (7 days after implantation of a trial device and the day of withdrawal of a trial device). We will disseminate the findings through regional, national, and international conferences and through peer-reviewed journals. UMIN Clinical Trials Registry (UMIN-CTR; R000033243) registered on 8 September 2017.

The evolution of anti-ulcer therapy with cimetidine. Is a single large nocturnal dose of cimetidine the right therapy for duodenal ulcer?

PubMed

Barbara, L; Corinaldesi, B; Stanghellini, V; Paternicò, A; Fabbri, L; Sacco, T

1986-01-01

Peptic ulcer results from the prevalence of agents causing endoluminal lesions over the defence mechanisms of the mucosa of the upper GI tract. Particularly, in the case of duodenal ulcer, the pathogenetic relevance of non-buffered acid secretion of the early nighttime period has been emphasized. This is indeed confirmed by the fact that a single night dose of 800 mg cimetidine has apparently been proved able--in numerous controlled clinical trials--to provide results that are similar to those obtained with the classic dose of 1 g daily or 400 mg twice daily. Our centre carried out a crossover double-blind controlled trial aimed at evaluating titrable acidity and pH during the 24-h period in seven patients with active duodenal ulcer. The single nighttime dose of cimetidine resulted in a significant and long-lasting inhibition of acid secretion during the entire night. During the day, secretory values returned to levels similar to those obtained with placebo, hence allowing normal digestive functions.

Somatosensory spatial attention modulates amplitudes, latencies, and latency jitter of laser-evoked brain potentials.

PubMed

Franz, Marcel; Nickel, Moritz M; Ritter, Alexander; Miltner, Wolfgang H R; Weiss, Thomas

2015-04-01

Several studies provided evidence that the amplitudes of laser-evoked potentials (LEPs) are modulated by attention. However, previous reports were based on across-trial averaging of LEP responses at the expense of losing information about intertrial variability related to attentional modulation. The aim of this study was to investigate the effects of somatosensory spatial attention on single-trial parameters (i.e., amplitudes, latencies, and latency jitter) of LEP components (N2 and P2). Twelve subjects participated in a sustained spatial attention paradigm while noxious laser stimuli (left hand) and noxious electrical stimuli (right hand) were sequentially delivered to the dorsum of the respective hand with nonnoxious air puffs randomly interspersed within the sequence of noxious stimuli. Participants were instructed to mentally count all stimuli (i.e., noxious and nonnoxious) applied to the attended location. Laser stimuli, presented to the attended hand (ALS), elicited larger single-trial amplitudes of the N2 component compared with unattended laser stimuli (ULS). In contrast, single-trial amplitudes of the P2 component were not significantly affected by spatial attention. Single-trial latencies of the N2 and P2 were significantly smaller for ALS vs. ULS. Additionally, the across-trial latency jitter of the N2 component was reduced for ALS. Conversely, the latency jitter of the P2 component was smaller for ULS compared with ALS. With the use of single-trial analysis, the study provided new insights into brain dynamics of LEPs related to spatial attention. Our results indicate that single-trial parameters of LEP components are differentially modulated by spatial attention. Copyright © 2015 the American Physiological Society.

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

PubMed

2015-07-27

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

Classification of Hand Grasp Kinetics and Types Using Movement-Related Cortical Potentials and EEG Rhythms.

PubMed

Jochumsen, Mads; Rovsing, Cecilie; Rovsing, Helene; Niazi, Imran Khan; Dremstrup, Kim; Kamavuako, Ernest Nlandu

2017-01-01

Detection of single-trial movement intentions from EEG is paramount for brain-computer interfacing in neurorehabilitation. These movement intentions contain task-related information and if this is decoded, the neurorehabilitation could potentially be optimized. The aim of this study was to classify single-trial movement intentions associated with two levels of force and speed and three different grasp types using EEG rhythms and components of the movement-related cortical potential (MRCP) as features. The feature importance was used to estimate encoding of discriminative information. Two data sets were used. 29 healthy subjects executed and imagined different hand movements, while EEG was recorded over the contralateral sensorimotor cortex. The following features were extracted: delta, theta, mu/alpha, beta, and gamma rhythms, readiness potential, negative slope, and motor potential of the MRCP. Sequential forward selection was performed, and classification was performed using linear discriminant analysis and support vector machines. Limited classification accuracies were obtained from the EEG rhythms and MRCP-components: 0.48 ± 0.05 (grasp types), 0.41 ± 0.07 (kinetic profiles, motor execution), and 0.39 ± 0.08 (kinetic profiles, motor imagination). Delta activity contributed the most but all features provided discriminative information. These findings suggest that information from the entire EEG spectrum is needed to discriminate between task-related parameters from single-trial movement intentions.

Single-Trial Normalization for Event-Related Spectral Decomposition Reduces Sensitivity to Noisy Trials

PubMed Central

Grandchamp, Romain; Delorme, Arnaud

2011-01-01

In electroencephalography, the classical event-related potential model often proves to be a limited method to study complex brain dynamics. For this reason, spectral techniques adapted from signal processing such as event-related spectral perturbation (ERSP) – and its variant event-related synchronization and event-related desynchronization – have been used over the past 20 years. They represent average spectral changes in response to a stimulus. These spectral methods do not have strong consensus for comparing pre- and post-stimulus activity. When computing ERSP, pre-stimulus baseline removal is usually performed after averaging the spectral estimate of multiple trials. Correcting the baseline of each single-trial prior to averaging spectral estimates is an alternative baseline correction method. However, we show that this method leads to positively skewed post-stimulus ERSP values. We eventually present new single-trial-based ERSP baseline correction methods that perform trial normalization or centering prior to applying classical baseline correction methods. We show that single-trial correction methods minimize the contribution of artifactual data trials with high-amplitude spectral estimates and are robust to outliers when performing statistical inference testing. We then characterize these methods in terms of their time–frequency responses and behavior compared to classical ERSP methods. PMID:21994498

How attention influences perceptual decision making: Single-trial EEG correlates of drift-diffusion model parameters

PubMed Central

Nunez, Michael D.; Vandekerckhove, Joachim; Srinivasan, Ramesh

2016-01-01

Perceptual decision making can be accounted for by drift-diffusion models, a class of decision-making models that assume a stochastic accumulation of evidence on each trial. Fitting response time and accuracy to a drift-diffusion model produces evidence accumulation rate and non-decision time parameter estimates that reflect cognitive processes. Our goal is to elucidate the effect of attention on visual decision making. In this study, we show that measures of attention obtained from simultaneous EEG recordings can explain per-trial evidence accumulation rates and perceptual preprocessing times during a visual decision making task. Models assuming linear relationships between diffusion model parameters and EEG measures as external inputs were fit in a single step in a hierarchical Bayesian framework. The EEG measures were features of the evoked potential (EP) to the onset of a masking noise and the onset of a task-relevant signal stimulus. Single-trial evoked EEG responses, P200s to the onsets of visual noise and N200s to the onsets of visual signal, explain single-trial evidence accumulation and preprocessing times. Within-trial evidence accumulation variance was not found to be influenced by attention to the signal or noise. Single-trial measures of attention lead to better out-of-sample predictions of accuracy and correct reaction time distributions for individual subjects. PMID:28435173

How attention influences perceptual decision making: Single-trial EEG correlates of drift-diffusion model parameters.

PubMed

Nunez, Michael D; Vandekerckhove, Joachim; Srinivasan, Ramesh

2017-02-01

Perceptual decision making can be accounted for by drift-diffusion models, a class of decision-making models that assume a stochastic accumulation of evidence on each trial. Fitting response time and accuracy to a drift-diffusion model produces evidence accumulation rate and non-decision time parameter estimates that reflect cognitive processes. Our goal is to elucidate the effect of attention on visual decision making. In this study, we show that measures of attention obtained from simultaneous EEG recordings can explain per-trial evidence accumulation rates and perceptual preprocessing times during a visual decision making task. Models assuming linear relationships between diffusion model parameters and EEG measures as external inputs were fit in a single step in a hierarchical Bayesian framework. The EEG measures were features of the evoked potential (EP) to the onset of a masking noise and the onset of a task-relevant signal stimulus. Single-trial evoked EEG responses, P200s to the onsets of visual noise and N200s to the onsets of visual signal, explain single-trial evidence accumulation and preprocessing times. Within-trial evidence accumulation variance was not found to be influenced by attention to the signal or noise. Single-trial measures of attention lead to better out-of-sample predictions of accuracy and correct reaction time distributions for individual subjects.

Micronutrient supplementation in adults with HIV infection

PubMed Central

Visser, Marianne E; Durao, Solange; Sinclair, David; Irlam, James H; Siegfried, Nandi

2017-01-01

Background Micronutrient deficiencies are common among adults living with HIV disease, particularly in low-income settings where the diet may be low in essential vitamins and minerals. Some micronutrients play critical roles in maintenance of the immune system, and routine supplementation could therefore be beneficial. This is an update of a Cochrane Review previously published in 2010. Objectives To assess whether micronutrient supplements are effective and safe in reducing mortality and HIV-related morbidity of HIV-positive adults (excluding pregnant women). Search methods We performed literature searches from January 2010 to 18 November 2016 for new randomized controlled trials (RCTs) of micronutrient supplements since the previous review included all trials identified from searches prior to 2010. We searched the CENTRAL (the Cochrane Library), Embase, and PubMed databases. Also we checked the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov trials registers. We also checked the reference lists of all new included trials. Selection criteria We included RCTs that compared supplements that contained either single, dual, or multiple micronutrients with placebo, no treatment, or other supplements. We excluded studies that were primarily designed to investigate the role of micronutrients for the treatment of HIV-positive participants with metabolic morbidity related to highly active antiretroviral therapy (HAART). Primary outcomes included all-cause mortality, morbidity, and disease progression. Data collection and analysis Two review authors independently selected trials for inclusion, and appraised trial quality for risk of bias. Where possible, we presented results as risk ratios (RR) for dichotomous variables, as hazard ratios (HRs) for time-to-event data, and as mean differences (MD) for continuous variables, each with 95% confidence intervals (CIs). Since we were often unable to pool the outcome data, we tabulated it for each comparison. We assessed the certainty of the evidence using the GRADE approach. Main results We included 33 trials with 10,325 participants, of which 17 trials were new trials. Ten trials compared a daily multiple micronutrient supplement to placebo in doses up to 20 times the dietary reference intake, and one trial compared a daily standard dose with a high daily dose of multivitamins. Nineteen trials compared supplementation with single or dual micronutrients (such as vitamins A and D, zinc, and selenium) to placebo, and three trials compared different dosages or combinations of micronutrients. Multiple micronutrients We conducted analyses across antiretroviral therapy (ART)-naive adults (3 trials, 1448 participants), adults on antiretroviral therapy (ART) (1 trial, 400 participants), and ART-naive adults with concurrent active tuberculosis (3 trials, 1429 participants). Routine multiple micronutrient supplementation may have little or no effect on mortality in adults living with HIV (RR 0.91, 95% CI 0.72 to 1.15; 7 trials, 2897 participants, low certainty evidence). Routine supplementation for up to two years may have little or no effect on the average of mean CD4+ cell count (MD 26.40 cells/mm³, 95% CI −22.91 to 75.70; 6 trials, 1581 participants, low certainty evidence), or the average of mean viral load (MD −0.1 log10viral copies, 95% CI −0.26 to 0.06; 4 trials, 840 participants, moderate certainty evidence). One additional trial in ART-naïve adults did report an increase in the time to reach a CD4+ cell count < 250 cells/mm³ after two years of high dose supplementation in Botswana (HR 0.48, 95% CI 0.26 to 0.88; 1 trial, 439 participants). However, the trial authors reported this effect only in the trial arm that received multiple micronutrients plus selenium (not either supplementation alone), which is inconsistent with the findings of other trials that used similar combinations of micronutrients and selenium. In one additional trial that compared high-dose multiple micronutrient supplementation with standard doses in people on ART, peripheral neuropathy was lower with high dose supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI 0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to increased adverse events (elevated alanine transaminase (ALT) levels) in the high dose group. Single or dual micronutrients None of the trials of single or dual micronutrient supplements were adequately powered to assess for effects on mortality or morbidity outcomes. No clinically significant changes in CD4 cell count (data not pooled, 14 trials, 2370 participants, very low or low certainty evidence) or viral load (data not pooled, seven studies, 1334 participants, very low or low certainty evidence), were reported. Supplementation probably does increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D: 4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty evidence) and may also increase blood concentrations of vitamin A (data not pooled, 3 trials, 495 participants, low certainty evidence), especially in those who are deficient. Authors' conclusions The analyses of the available trials have not revealed consistent clinically important benefits with routine multiple micronutrient supplementation in people living with HIV. Larger trials might reveal small but important effects. These findings should not be interpreted as a reason to deny micronutrient supplements for people living with HIV where specific deficiencies are found or where the person's diet is insufficient to meet the recommended daily allowance of vitamins and minerals. Micronutrient supplements for non-pregnant adults with HIV infection Cochrane researchers conducted a review of the effects of micronutrient supplements for people living with HIV. This is an update of a Cochrane Review previously published in 2010. After searching for relevant trials up to 18 November 2016, the review authors included 33 trials. Thirteen of these trials included people not on HIV treatment and were conducted in Thailand, Peru, and eight African countries. Nineteen trials included people on HIV treatment and were conducted in North America, Europe, Brazil, Singapore, Thailand, Botswana, and Uganda. One trial from China did not state whether people living with HIV were on treatment or not. Some trials looked at the effects of taking supplements with multiple micronutrients whereas others looked at supplementation with single vitamins or minerals. What are micronutrient supplements and how might they help people living with HIV? Micronutrient supplements contain vitamins or minerals, or both, that are essential to good health. Many of these vitamins play important roles in maintaining the human immune system, which helps to fight off infections. Infection with HIV causes a progressive destruction of the immune system, which leaves people vulnerable to frequent infections. Many people living with HIV, especially in low-income countries, are also undernourished and many consume diets deficient that these essential micronutrients. Supplementation could therefore help people living with HIV to stay healthy for longer by strengthening their immune system or assisting recovery from infections. What the research says Multiple micronutrients Providing a daily supplement that contains multiple vitamins and minerals may have little or no effect on reducing deaths in people living with HIV, whether they are taking antiretroviral drugs or not (low certainty evidence). Daily supplements may have little or no effect on HIV disease progression as measured by CD4 cell count (low certainty evidence) or HIV viral load (low or moderate certainty evidence). Single or dual micronutrients We do not know whether supplements that contain single vitamins or minerals reduce deaths (very low certainty evidence) or slow disease progression (very low/low certainty evidence) in people living with HIV. Supplementation with vitamin A, D, zinc, or selenium may improve the level of each vitamin in a person's blood, especially those with low levels before supplementation (low/moderate certainty evidence). These findings do not mean that an adequate dietary intake for people living with HIV is not important. It is also not a reason to deny micronutrient supplements for those in whom a deficiency has been clinically demonstrated, or who are unlikely to meet the recommended daily allowance of vitamins and minerals. PMID:28518221

Vitamin K for the primary prevention of cardiovascular disease.

PubMed

Hartley, Louise; Clar, Christine; Ghannam, Obadah; Flowers, Nadine; Stranges, Saverio; Rees, Karen

2015-09-21

A deficiency in vitamin K has been associated with increased calcium deposition and coronary artery calcification, which may lead to cardiovascular disease. To determine the effectiveness of vitamin K supplementation as a single nutrient supplement for the primary prevention of cardiovascular disease. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8 of 12, 2014); MEDLINE (Ovid, 1946 to September week 2 2014); EMBASE Classic + EMBASE (Ovid, 1947 to September 18 2014); Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index, Science (CPCI-S) (both 1990 to 17 September 2014) on Web of Science (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database (Issue 3 of 4, 2014). We searched trial registers and reference lists of reviews for further studies. We applied no language restrictions. We included randomised controlled trials of vitamin K supplementation as a single nutrient supplement, lasting at least three months, and involving healthy adults or adults at high risk of cardiovascular disease. The comparison group was no intervention or placebo. The outcomes of interest were cardiovascular disease clinical events and cardiovascular disease risk factors. Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias. We included only one small trial (60 participants randomised) which overall was judged to be at low risk of bias. The study examined two doses of menaquinone (vitamin K2) over 3 months in healthy participants aged 40 to 65 years. The primary focus of the trial was to examine the effects of menaquinone (subtype MK7) on different matrix Gla proteins (MGP - vitamin K dependent proteins in the vessel wall) at different doses, but the authors also reported blood pressure and lipid levels. The trial did not report on our primary outcomes (cardiovascular disease clinical events) as it was small, short term and conducted in healthy participants.In terms of cardiovascular disease risk factors, no effects were seen for vitamin K2 on blood pressure or lipid levels, although the trial was small and findings are limited. The trial did not report any of our other secondary outcomes. The very limited results of this review highlight the lack of evidence currently available to determine the effectiveness of vitamin K supplementation for the primary prevention of cardiovascular disease, and demonstrate the need for further high quality trials in this area.

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework.

PubMed

Jull, J; Whitehead, M; Petticrew, M; Kristjansson, E; Gough, D; Petkovic, J; Volmink, J; Weijer, C; Taljaard, M; Edwards, S; Mbuagbaw, L; Cookson, R; McGowan, J; Lyddiatt, A; Boyer, Y; Cuervo, L G; Armstrong, R; White, H; Yoganathan, M; Pantoja, T; Shea, B; Pottie, K; Norheim, O; Baird, S; Robberstad, B; Sommerfelt, H; Asada, Y; Wells, G; Tugwell, P; Welch, V

2017-09-25

Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. A randomised trial can usefully be classified as 'health equity relevant' if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as 'health equity relevant' may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Beta-adrenoreceptor blockade abolishes atomoxetine-induced risk taking.

PubMed

Yang, Fan Nils; Pan, Jing Samantha; Li, Xinwang

2016-01-01

Clinical studies have shown that patients with exaggerated risk-taking tendencies have high baseline levels of norepinephrine. In this work, we systemically manipulated norepinephrine levels in rats and studied their behavioral changes in a probabilistic discounting task, which is a paradigm for gauging risk taking. This study aims to explore the effects of the selective norepinephrine reuptake inhibitor (atomoxetine at doses of 0.6, 1.0 and 1.8 mg/kg), and receptor selective antagonists (propranolol at a single dose of 1.0/kg, and prazosin at a single dose of 0.1 mg/kg), on risk taking using a probabilistic discounting task. In this task, there were two levers available to rats: pressing the 'small/certain' lever guaranteed a single food pellet, and pressing the 'large/risky' lever yielded either four pellets or none. The probability of receiving four food pellets decreased across the four experimental blocks from 100% to 12.5%. Atomoxetine increased the tendency to choose the large/risky lever. It significantly reduced the lose-shift effect (i.e. pressing a different lever after losing a trial), but did not affect the win-stay effect (i.e. pressing the same lever after winning a trial). Furthermore, co-administration of beta-adrenoreceptor antagonist, propranolol, eliminated the effects of atomoxetine on risk taking and the lose-shift effect; but co-administration of alpha1-adrenoreceptor antagonist, prazosin, did not. Atomoxetine boosted NE levels and increased risk taking. This was because atomoxetine decreased rats' sensitivity to losses. These effects were likely mediated by beta-adrenoreceptor. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of fat on serum 25-hydroxyvitamin D levels after a single oral dose of vitamin D in young healthy adults: a double-blind randomized placebo-controlled study.

PubMed

Raimundo, Fabiana Viegas; Lang, Maria Augusta Britto; Scopel, Luciano; Marcondes, Natália Aydos; Araújo, Mirna Griselda Anocibar; Faulhaber, Gustavo Adolpho Moreira; Furlanetto, Tania Weber

2015-04-01

This double-blind placebo-controlled trial evaluated serum 25-hydroxyvitamin D [25(OH)D] levels after the oral intake of a single dose of cholecalciferol during one of the three meals, containing different amounts of fat or placebo. Sixty-four healthy medical residents or students of a university hospital in Porto Alegre, latitude 30° S, Brazil, were divided into four groups. Three groups received a single 50,000 IU oral dose of cholecalciferol during a meal containing 0 g (Group 1), 15 g (Group 2) or 30 g (Group 3) of fat, and one group received placebo (Group 4), according to randomization. Serum 25(OH)D, parathyroid hormone, total calcium, albumin, magnesium, and creatinine levels, and urinary calcium, magnesium, and creatinine levels were measured at baseline and after 14 days. Baseline mean serum 25(OH)D levels were low in all groups. Vitamin D given during breakfast increased the mean change of serum 25(OH)D levels, when compared to placebo. Furthermore, the intake of fat with vitamin D increased the mean change of serum 25(OH)D levels. A single oral dose of vitamin D given with food increased mean serum 25(OH)D levels, after 2 weeks, and the mean increase was larger, when the meal had at least 15 g of fat. These findings can have important implications to oral vitamin D supplementation.

Comparison of two independent systematic reviews of trials of recombinant human bone morphogenetic protein-2 (rhBMP-2): the Yale Open Data Access Medtronic Project.

PubMed

Low, Jeffrey; Ross, Joseph S; Ritchie, Jessica D; Gross, Cary P; Lehman, Richard; Lin, Haiqun; Fu, Rongwei; Stewart, Lesley A; Krumholz, Harlan M

2017-02-15

It is uncertain whether the replication of systematic reviews, particularly those with the same objectives and resources, would employ similar methods and/or arrive at identical findings. We compared the results and conclusions of two concurrent systematic reviews undertaken by two independent research teams provided with the same objectives, resources, and individual participant-level data. Two centers in the USA and UK were each provided with participant-level data on 17 multi-site clinical trials of recombinant human bone morphogenetic protein-2 (rhBMP-2). The teams were blinded to each other's methods and findings until after publication. We conducted a retrospective structured comparison of the results of the two systematic reviews. The main outcome measures included (1) trial inclusion criteria; (2) statistical methods; (3) summary efficacy and risk estimates; and (4) conclusions. The two research teams' meta-analyses inclusion criteria were broadly similar but differed slightly in trial inclusion and research methodology. They obtained similar results in summary estimates of most clinical outcomes and adverse events. Center A incorporated all trials into summary estimates of efficacy and harms, while Center B concentrated on analyses stratified by surgical approach. Center A found a statistically significant, but small, benefit whereas Center B reported no advantage. In the analysis of harms, neither showed an increased cancer risk at 48 months, although Center B reported a significant increase at 24 months. Conclusions reflected these differences in summary estimates of benefit balanced with small but potentially important risk of harm. Two independent groups given the same research objectives, data, resources, funding, and time produced broad general agreement but differed in several areas. These differences, the importance of which is debatable, indicate the value of the availability of data to allow for more than a single approach and a single interpretation of the data. PROSPERO CRD42012002040 and CRD42012001907 .

Assessing the Depth of Cognitive Processing as the Basis for Potential User-State Adaptation

PubMed Central

Nicolae, Irina-Emilia; Acqualagna, Laura; Blankertz, Benjamin

2017-01-01

Objective: Decoding neurocognitive processes on a single-trial basis with Brain-Computer Interface (BCI) techniques can reveal the user's internal interpretation of the current situation. Such information can potentially be exploited to make devices and interfaces more user aware. In this line of research, we took a further step by studying neural correlates of different levels of cognitive processes and developing a method that allows to quantify how deeply presented information is processed in the brain. Methods/Approach: Seventeen participants took part in an EEG study in which we evaluated different levels of cognitive processing (no processing, shallow, and deep processing) within three distinct domains (memory, language, and visual imagination). Our investigations showed gradual differences in the amplitudes of event-related potentials (ERPs) and in the extend and duration of event-related desynchronization (ERD) which both correlate with task difficulty. We performed multi-modal classification to map the measured correlates of neurocognitive processing to the corresponding level of processing. Results: Successful classification of the neural components was achieved, which reflects the level of cognitive processing performed by the participants. The results show performances above chance level for each participant and a mean performance of 70–90% for all conditions and classification pairs. Significance: The successful estimation of the level of cognition on a single-trial basis supports the feasibility of user-state adaptation based on ongoing neural activity. There is a variety of potential use cases such as: a user-friendly adaptive design of an interface or the development of assistance systems in safety critical workplaces. PMID:29046625

Assessing the Depth of Cognitive Processing as the Basis for Potential User-State Adaptation.

PubMed

Nicolae, Irina-Emilia; Acqualagna, Laura; Blankertz, Benjamin

2017-01-01

Objective: Decoding neurocognitive processes on a single-trial basis with Brain-Computer Interface (BCI) techniques can reveal the user's internal interpretation of the current situation. Such information can potentially be exploited to make devices and interfaces more user aware. In this line of research, we took a further step by studying neural correlates of different levels of cognitive processes and developing a method that allows to quantify how deeply presented information is processed in the brain. Methods/Approach: Seventeen participants took part in an EEG study in which we evaluated different levels of cognitive processing (no processing, shallow, and deep processing) within three distinct domains (memory, language, and visual imagination). Our investigations showed gradual differences in the amplitudes of event-related potentials (ERPs) and in the extend and duration of event-related desynchronization (ERD) which both correlate with task difficulty. We performed multi-modal classification to map the measured correlates of neurocognitive processing to the corresponding level of processing. Results: Successful classification of the neural components was achieved, which reflects the level of cognitive processing performed by the participants. The results show performances above chance level for each participant and a mean performance of 70-90% for all conditions and classification pairs. Significance: The successful estimation of the level of cognition on a single-trial basis supports the feasibility of user-state adaptation based on ongoing neural activity. There is a variety of potential use cases such as: a user-friendly adaptive design of an interface or the development of assistance systems in safety critical workplaces.

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.

Relationships between authorship contributions and authors' industry financial ties among oncology clinical trials.

PubMed

Rose, Susannah L; Krzyzanowska, Monika K; Joffe, Steven

2010-03-10

PURPOSE To test the hypothesis that authors who play key scientific roles in oncology clinical trials, and who therefore have increased influence over the design, analysis, interpretation or reporting of trials, are more likely than those who do not play such roles to have financial ties to industry. METHODS Data were abstracted from all trials (n = 235) of drugs or biologic agents published in the Journal of Clinical Oncology between January 1, 2006 and June 30, 2007. Article-level data included sponsorship, age group (adult v pediatric), phase, single versus multicenter, country (United States v other), and number of authors. Author-level data (n = 2,927) included financial ties (eg, employment, consulting) and performance of key scientific roles (ie, conception/design, analysis/interpretation, or manuscript writing). Associations between performance of key roles and financial ties, adjusting for article-level covariates, were examined using generalized linear mixed models. Results One thousand eight hundred eighty-one authors (64%) reported performing at least one key role, and 842 authors (29%) reported at least one financial tie. Authors who reported performing a key role were more likely than other authors to report financial ties to industry (adjusted odds ratio [OR], 4.3; 99% CI, 3.0 to 6.0; P < .0001). The association was stronger among trials with, compared with those without, industry funding (OR, 5.0 [99% CI, 3.4 to 7.5] v OR, 2.5 [99% CI, 1.3 to 4.8]), but was present regardless of sponsorship. CONCLUSION Authors who perform key roles in the conception and design, analysis, and interpretation, or reporting of oncology clinical trials are more likely than authors who do not perform such roles to have financial ties to industry.

Relationships Between Authorship Contributions and Authors' Industry Financial Ties Among Oncology Clinical Trials

PubMed Central

Rose, Susannah L.; Krzyzanowska, Monika K.; Joffe, Steven

2010-01-01

Purpose To test the hypothesis that authors who play key scientific roles in oncology clinical trials, and who therefore have increased influence over the design, analysis, interpretation or reporting of trials, are more likely than those who do not play such roles to have financial ties to industry. Methods Data were abstracted from all trials (n = 235) of drugs or biologic agents published in the Journal of Clinical Oncology between January 1, 2006 and June 30, 2007. Article-level data included sponsorship, age group (adult v pediatric), phase, single versus multicenter, country (United States v other), and number of authors. Author-level data (n = 2,927) included financial ties (eg, employment, consulting) and performance of key scientific roles (ie, conception/design, analysis/interpretation, or manuscript writing). Associations between performance of key roles and financial ties, adjusting for article-level covariates, were examined using generalized linear mixed models. Results One thousand eight hundred eighty-one authors (64%) reported performing at least one key role, and 842 authors (29%) reported at least one financial tie. Authors who reported performing a key role were more likely than other authors to report financial ties to industry (adjusted odds ratio [OR], 4.3; 99% CI, 3.0 to 6.0; P < .0001). The association was stronger among trials with, compared with those without, industry funding (OR, 5.0 [99% CI, 3.4 to 7.5] v OR, 2.5 [99% CI, 1.3 to 4.8]), but was present regardless of sponsorship. Conclusion Authors who perform key roles in the conception and design, analysis, and interpretation, or reporting of oncology clinical trials are more likely than authors who do not perform such roles to have financial ties to industry. PMID:20065190

Intravenous iron isomaltoside 1000 (Monofer®) reduces postoperative anaemia in preoperatively non-anaemic patients undergoing elective or subacute coronary artery bypass graft, valve replacement or a combination thereof: a randomized double-blind placebo-controlled clinical trial (the PROTECT trial).

PubMed

Johansson, P I; Rasmussen, A S; Thomsen, L L

2015-10-01

This trial explores whether intravenous iron isomaltoside 1000 (Monofer®) results in a better regeneration of haemoglobin levels and prevents anaemia compared to placebo in preoperative non-anaemic patients undergoing cardiac surgery. The trial is a prospective, double-blind, comparative, placebo-controlled trial of 60 non-anaemic patients undergoing cardiac surgery. The patients were randomized 1:1 to either 1000 mg intravenous iron isomaltoside 1000 administered perioperatively by infusion or placebo. Mean preoperative haemoglobin in the active treatment group was 14·3 g/dl vs. 14·0 g/dl in the placebo group. At discharge 5 days after surgery, haemoglobin levels were reduced to 10·7 and 10·5 g/dl, respectively. One month after surgery, haemoglobin concentration had increased to an average of 12·6 g/dl vs. 11·8 g/dl (p = 0·012) and significantly more patients were non-anaemic in the intravenous iron isomaltoside 1000-treated group compared to the placebo group (38·5% vs. 8·0%; p = 0·019). There were no differences in side-effects between the groups. A single perioperative 1000 mg dose of intravenous iron isomaltoside 1000 significantly increased the haemoglobin level and prevented anaemia 4 weeks after surgery, with a short-term safety profile similar to placebo. Future trials on potential clinical benefits of preoperative treatment with intravenous iron in non-anaemic patients are needed. © 2015 The Authors ISBT Science Series published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

Extensive but not Limited Repeated Trials in Passive Avoidance Task Induce Stress-like Symptoms and Affect Memory Function in Rats.

PubMed

Tabassum, Saiqa; Haider, Saida

2018-02-10

Stressful and emotionally arousing experiences are remembered, and previous reports show that repeated exposure to stressful condition enhances emotional learning. However, the usefulness of the repeated exposure depends on the intensity and duration. Although repeated training as a strategy to improve memory performance is receiving increased attention from researchers, repeated training may induce stressful effects that have not yet been considered. The present study investigated whether exposure to repetitive learning trials with limited or extensive durations in a passive avoidance task (PAT) would be beneficial or harmful to emotional memory performance in rats. Rats were exposed to repetitive learning trials for two different durations in the limited exposure (exposure to four repetitive trials) and extensive exposure groups (exposure to 16 repetitive trials) in a single day to compare the impact of both conditions on rat emotional memory performance. Alterations in corticosterone content and associated oxidative and neurochemical systems were assessed to explore the underlying mechanism responsible for changes in emotional memory. Following extensive exposure, a negative impact on emotional memory was observed compared with the limited exposure group. A lack of any further improvement in memory function following extensive training exposure was supported by increased corticosterone levels, decreased 5-hydroxytryptamine (5-HT) levels and abnormal oxidative stress levels, which may induce negative effects on memory consolidation. It is suggested that limited exposure to repetitive learning trials is more useful for studying improvement in emotional memory, whereas extensive exposure may produce chronic stress-like condition that can be detrimental and responsible for compromised memory performance. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Single-Level Degenerative Cervical Disc Disease and Driving Disability: Results from a Prospective, Randomized Trial

PubMed Central

Kelly, Michael P.; Mitchell, M. David; Hacker, Robert J.; Riew, K. Daniel; Sasso, Rick C.

2013-01-01

Study Design Post hoc analysis of prospective, randomized trial. Objective To investigate the disability associated with driving and single-level degenerative, cervical disc disease and to investigate the effect of surgery on driving disability. Methods Post hoc analysis of data obtained from three sites participating in a multicenter, randomized, controlled trial comparing cervical disc arthroplasty (TDA) with anterior cervical discectomy and fusion (ACDF). The driving subscale of the Neck Disability Index (NDI) was analyzed for all patients. A dichotomous severity score was created from the NDI. Statistical comparisons were made within and between groups. Results Two-year follow-up was available for 118/135 (87%) patients. One half of the study population (49.6%) reported moderate or severe preoperative driving difficulty. This disability associated with driving was similar among the two groups (ACDF: 2.5 ± 1.1, TDA: 2.6 ± 1.0, p = 0.646). The majority of patients showed improvement, with no or little driving disability, at the sixth postoperative week (ACDF: 75%, TDA: 90%, p = 0.073). At no follow-up point did a difference exist between groups according to the severity index. Conclusions Many patients suffering from radiculopathy or myelopathy from cervical disc disease are limited in their ability to operate an automobile. Following anterior cervical spine surgery, most patients are able to return to comfortable driving at 6 weeks. PMID:24436875

Foraging enrichment for stabled horses: effects on behaviour and selection.

PubMed

Goodwin, D; Davidson, H P B; Harris, P

2002-11-01

The restricted access to pasture experienced by many competition horses has been linked to the exhibition of stereotypic and redirected behaviour patterns. It has been suggested that racehorses provided with more than one source of forage are less likely to perform these patterns; however, the reasons for this are currently unclear. To investigate this in 4 replicated trials, up to 12 horses were introduced into each of 2 identical stables containing a single forage, or 6 forages for 5 min. To detect novelty effects, in the first and third trials the single forage was hay. In the second and fourth, it was the preferred forage from the preceding trial. Trials were videotaped and 12 mutually exclusive behaviour patterns compared. When hay was presented as the single forage (Trials 1 and 3), all recorded behaviour patterns were significantly different between stables; e.g. during Trial 3 in the 'Single' stable, horses looked over the stable door more frequently (P<0.001), moved for longer (P<0.001), foraged on straw bedding longer (P<0.001), and exhibited behaviour indicative of motivation to search for alternative resources (P<0.001) more frequently. When a previously preferred forage was presented as the single forage (Trials 2 and 4) behaviour was also significantly different between stables, e.g in Trial 4 horses looked out over the stable door more frequently (P<0.005) and foraged for longer in their straw bedding (P<0.005). Further study is required to determine whether these effects persist over longer periods. However, these trials indicate that enrichment of the stable environment through provision of multiple forages may have welfare benefits for horses, in reducing straw consumption and facilitating the expression of highly motivated foraging behaviour.

Provision of well-water treatment units to 600 households in Bangladesh: A longitudinal analysis of urinary arsenic indicates fading utility.

PubMed

Sanchez, Tiffany R; Levy, Diane; Shahriar, Mohammad Hasan; Uddin, Mohammad Nasir; Siddique, Abu B; Graziano, Joseph H; Lomax-Luu, Angela; van Geen, Alexander; Gamble, Mary V

2016-09-01

Millions of villagers in Bangladesh remain exposed to high levels of arsenic (As) from drinking untreated well-water even though the scale of the problem was recognized 15years ago. Water treatment at the household-level has been promoted as a viable complement but few longitudinal studies of their efficacy using an objective measure of exposure have been conducted. Participants (N=622) of a nutrition trial in Araihazar, Bangladesh were each provided with READ-F filters at the beginning of the study and encouraged to use them over the 6month duration of the intervention. Well-water As, treated water As, and urinary As were monitored periodically during the trial and measured again one year after the trial ended. The READ-F filters were initially well received and median urinary As levels for participants declined from 117μg/L to 51μg/L within a single week. However, median urinary As levels gradually rose back to 126μg/L by the end of the trial. Fifty filters were replaced over the course of the trial because of insufficient As removal or reduced flow. With these exceptions, most of the treated water met the WHO guideline for As in drinking water of 10μg/L. One year after the nutritional trial ended, 95% of participants had abandoned their filter citing inconvenience as the primary reason. At that time, median urinary As levels for 10 participants who had switched to a nearby low-As well had declined to 63μg/L. Participants were probably no longer using the READ-F filter long before the 6month nutritional intervention ended despite claiming that they were using them. Household-level treatment is likely to continue to play a minor role in the effort to reduce As exposure in Bangladesh. Understanding the limitations of such expensive interventions is important for future policy regarding As mitigation. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of Critical Power and W' Derived From 2 or 3 Maximal Tests.

PubMed

Simpson, Len Parker; Kordi, Mehdi

2017-07-01

Typically, accessing the asymptote (critical power; CP) and curvature constant (W') parameters of the hyperbolic power-duration relationship requires multiple constant-power exhaustive-exercise trials spread over several visits. However, more recently single-visit protocols and personal power meters have been used. This study investigated the practicality of using a 2-trial, single-visit protocol in providing reliable CP and W' estimates. Eight trained cyclists underwent 3- and 12-min maximal-exercise trials in a single session to derive (2-trial) CP and W' estimates. On a separate occasion a 5-min trial was performed, providing a 3rd trial to calculate (3-trial) CP and W'. There were no differences in CP (283 ± 66 vs 282 ± 65 W) or W' (18.72 ± 6.21 vs 18.27 ± 6.29 kJ) obtained from either the 2-trial or 3-trial method, respectively. After 2 familiarization sessions (completing a 3- and a 12-min trial on both occasions), both CP and W' remained reliable over additional separate measurements. The current study demonstrates that after 2 familiarization sessions, reliable CP and W' parameters can be obtained from trained cyclists using only 2 maximal-exercise trials. These results offer practitioners a practical, time-efficient solution for incorporating power-duration testing into applied athlete support.

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

Minimizing adverse events while maintaining clinical improvement in a pediatric attention-deficit/hyperactivity disorder crossover trial with dextroamphetamine and methylphenidate.

PubMed

Ramtvedt, Bjørn E; Aabech, Henning S; Sundet, Kjetil

2014-04-01

The purpose of this study was to investigate whether the availability of both dextroamphetamine and methylphenidate provides an opportunity to minimize adverse events in a pediatric attention-deficit/hyperactivity disorder (ADHD) stimulant trial. Thirty-six medication-naïve children 9-14 years of age, diagnosed with ADHD, were enrolled for 6 weeks in a crossover trial, with 2 weeks of methylphenidate, dextroamphetamine, and a placebo in a randomly assigned, counterbalanced sequence. Barkley's Side-Effect Rating Scale (SERS), rated by parents, was used to assess adverse events. SERS were available for 34 children, and data were analyzed both at the group and the single-subject level. The side-effect profiles of dextroamphetamine and methylphenidate appeared similar at the group level. Overall, insomnia and decreased appetite were the only adverse events associated with the stimulants as compared with placebo. No significant increase from placebo to stimulant conditions was detected on SERS items reflecting emotional symptoms. Furthermore, dextroamphetamine and methylphenidate did not differ from each other on any SERS item, except that dextroamphetamine was associated with higher severity of "insomnia" and a higher prevalence of "unusually happy." Single-subject analyses showed that one or more adverse events were reported in 14 children (41%), and were evenly distributed between those with dextroamphetamine as the drug that showed the greatest reduction in their ADHD symptoms ("best drug") and those with methylphenidate as their best drug. Among children in whom both stimulants were associated with a decrease in ADHD symptoms, a clinically valid difference between the two stimulants in total adverse events score was found in 7 (39%) of the 18 cases. In these children, the availability of both stimulants provided an opportunity to minimize adverse events, while maintaining a reduction in ADHD symptoms. The availability of both dextroamphetamine and methylphenidate may contribute to minimize adverse events in a subsample of children in pediatric ADHD stimulant trials. The study was first registered in clinical trials September 28, 2010. Clinical Trials.gov Identifier: NCT01220440.

Optimization of Support Vector Machine (SVM) for Object Classification

NASA Technical Reports Server (NTRS)

Scholten, Matthew; Dhingra, Neil; Lu, Thomas T.; Chao, Tien-Hsin

2012-01-01

The Support Vector Machine (SVM) is a powerful algorithm, useful in classifying data into species. The SVMs implemented in this research were used as classifiers for the final stage in a Multistage Automatic Target Recognition (ATR) system. A single kernel SVM known as SVMlight, and a modified version known as a SVM with K-Means Clustering were used. These SVM algorithms were tested as classifiers under varying conditions. Image noise levels varied, and the orientation of the targets changed. The classifiers were then optimized to demonstrate their maximum potential as classifiers. Results demonstrate the reliability of SVM as a method for classification. From trial to trial, SVM produces consistent results.

Rapid learning dynamics in individual honeybees during classical conditioning.

PubMed

Pamir, Evren; Szyszka, Paul; Scheiner, Ricarda; Nawrot, Martin P

2014-01-01

Associative learning in insects has been studied extensively by a multitude of classical conditioning protocols. However, so far little emphasis has been put on the dynamics of learning in individuals. The honeybee is a well-established animal model for learning and memory. We here studied associative learning as expressed in individual behavior based on a large collection of data on olfactory classical conditioning (25 datasets, 3298 animals). We show that the group-averaged learning curve and memory retention score confound three attributes of individual learning: the ability or inability to learn a given task, the generally fast acquisition of a conditioned response (CR) in learners, and the high stability of the CR during consecutive training and memory retention trials. We reassessed the prevailing view that more training results in better memory performance and found that 24 h memory retention can be indistinguishable after single-trial and multiple-trial conditioning in individuals. We explain how inter-individual differences in learning can be accommodated within the Rescorla-Wagner theory of associative learning. In both data-analysis and modeling we demonstrate how the conflict between population-level and single-animal perspectives on learning and memory can be disentangled.

Rapid learning dynamics in individual honeybees during classical conditioning

PubMed Central

Pamir, Evren; Szyszka, Paul; Scheiner, Ricarda; Nawrot, Martin P.

2014-01-01

Associative learning in insects has been studied extensively by a multitude of classical conditioning protocols. However, so far little emphasis has been put on the dynamics of learning in individuals. The honeybee is a well-established animal model for learning and memory. We here studied associative learning as expressed in individual behavior based on a large collection of data on olfactory classical conditioning (25 datasets, 3298 animals). We show that the group-averaged learning curve and memory retention score confound three attributes of individual learning: the ability or inability to learn a given task, the generally fast acquisition of a conditioned response (CR) in learners, and the high stability of the CR during consecutive training and memory retention trials. We reassessed the prevailing view that more training results in better memory performance and found that 24 h memory retention can be indistinguishable after single-trial and multiple-trial conditioning in individuals. We explain how inter-individual differences in learning can be accommodated within the Rescorla–Wagner theory of associative learning. In both data-analysis and modeling we demonstrate how the conflict between population-level and single-animal perspectives on learning and memory can be disentangled. PMID:25309366

Single-trial detection of visual evoked potentials by common spatial patterns and wavelet filtering for brain-computer interface.

PubMed

Tu, Yiheng; Huang, Gan; Hung, Yeung Sam; Hu, Li; Hu, Yong; Zhang, Zhiguo

2013-01-01

Event-related potentials (ERPs) are widely used in brain-computer interface (BCI) systems as input signals conveying a subject's intention. A fast and reliable single-trial ERP detection method can be used to develop a BCI system with both high speed and high accuracy. However, most of single-trial ERP detection methods are developed for offline EEG analysis and thus have a high computational complexity and need manual operations. Therefore, they are not applicable to practical BCI systems, which require a low-complexity and automatic ERP detection method. This work presents a joint spatial-time-frequency filter that combines common spatial patterns (CSP) and wavelet filtering (WF) for improving the signal-to-noise (SNR) of visual evoked potentials (VEP), which can lead to a single-trial ERP-based BCI.

Cervical Disk Replacement With Discover Versus Fusion in a Single-Level Cervical Disk Disease: A Prospective Single-Center Randomized Trial With a Minimum 2-Year Follow-up.

PubMed

Rožanković, Marjan; Marasanov, Sergej M; Vukić, Miroslav

2017-06-01

Prospective randomized study. To compare the clinical outcome after Discover arthroplasty versus anterior cervical discectomy and fusion (ACDF) in patients treated for symptomatic single-level cervical disk disease. ACDF is still the gold standard for surgical treatment of cervical spine degenerative disk disease. However, results of many studies suggest that it may cause degenerative changes at levels immediately above and below the fusion, known as adjacent segment degenerative disease. Cervical arthroplasty has recently been introduced as an alternative to standard procedure of ACDF. It showed decreased surgical morbidity, decreased complications from postoperative immobilization, and an earlier return to previous level of function. A total of 105 consecutive patients with single-level cervical disk disease, producing radiculopathy and/or myelopathy were randomly divided into groups to undergo ACDF or Discover arthroplasty. All patients were evaluated with preoperative and postoperative serial radiographic studies and clinically, using Neck Disability Index, Visual Analog Scale and neurological status at 3, 6, 12, and 24 months. The results of our study indicate that cervical arthroplasty using Discover Artificial Cervical Disc provides favorable clinical and radiologic outcomes in a follow-up period of 24 months. There has been significant improvement in clinical parameters, Visual Analog Scale and Neck Disability Index, at 3, 6, 12, and 24 months in arthroplasty group comparing to control group. The Discover artificial cervical disc replacement offers favorable outcome compared with ACDF for a single-level cervical disk disease at short-term and long-term follow-up.

Single treatments that have lasting effects: some thoughts on the antidepressant effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin.

PubMed

Young, Simon N

2013-03-01

Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research with animal models of depression suggesting that glutamate may be involved in depression, the N-methyl-D-aspartate antagonist ketamine has been tested in several trials. A single dose decreased depression for up to a week. The reported effects of the use of mushrooms containing psilocybin by a number of cultures around the world has stimulated several trials showing beneficial effects of a single dose of psilocybin for over a year in healthy people, and for up to 3 months in patients with anxiety disorders who have advanced cancer. This article discusses these studies, their rationale, their possible mechanisms of action, the future clinical research required to establish these therapies and the basic research required to optimize single treatments that have lasting effects.

Group-Level EEG-Processing Pipeline for Flexible Single Trial-Based Analyses Including Linear Mixed Models

PubMed Central

Frömer, Romy; Maier, Martin; Abdel Rahman, Rasha

2018-01-01

Here we present an application of an EEG processing pipeline customizing EEGLAB and FieldTrip functions, specifically optimized to flexibly analyze EEG data based on single trial information. The key component of our approach is to create a comprehensive 3-D EEG data structure including all trials and all participants maintaining the original order of recording. This allows straightforward access to subsets of the data based on any information available in a behavioral data structure matched with the EEG data (experimental conditions, but also performance indicators, such accuracy or RTs of single trials). In the present study we exploit this structure to compute linear mixed models (LMMs, using lmer in R) including random intercepts and slopes for items. This information can easily be read out from the matched behavioral data, whereas it might not be accessible in traditional ERP approaches without substantial effort. We further provide easily adaptable scripts for performing cluster-based permutation tests (as implemented in FieldTrip), as a more robust alternative to traditional omnibus ANOVAs. Our approach is particularly advantageous for data with parametric within-subject covariates (e.g., performance) and/or multiple complex stimuli (such as words, faces or objects) that vary in features affecting cognitive processes and ERPs (such as word frequency, salience or familiarity), which are sometimes hard to control experimentally or might themselves constitute variables of interest. The present dataset was recorded from 40 participants who performed a visual search task on previously unfamiliar objects, presented either visually intact or blurred. MATLAB as well as R scripts are provided that can be adapted to different datasets. PMID:29472836

Statistical evaluation of surrogate endpoints with examples from cancer clinical trials.

PubMed

Buyse, Marc; Molenberghs, Geert; Paoletti, Xavier; Oba, Koji; Alonso, Ariel; Van der Elst, Wim; Burzykowski, Tomasz

2016-01-01

A surrogate endpoint is intended to replace a clinical endpoint for the evaluation of new treatments when it can be measured more cheaply, more conveniently, more frequently, or earlier than that clinical endpoint. A surrogate endpoint is expected to predict clinical benefit, harm, or lack of these. Besides the biological plausibility of a surrogate, a quantitative assessment of the strength of evidence for surrogacy requires the demonstration of the prognostic value of the surrogate for the clinical outcome, and evidence that treatment effects on the surrogate reliably predict treatment effects on the clinical outcome. We focus on these two conditions, and outline the statistical approaches that have been proposed to assess the extent to which these conditions are fulfilled. When data are available from a single trial, one can assess the "individual level association" between the surrogate and the true endpoint. When data are available from several trials, one can additionally assess the "trial level association" between the treatment effect on the surrogate and the treatment effect on the true endpoint. In the latter case, the "surrogate threshold effect" can be estimated as the minimum effect on the surrogate endpoint that predicts a statistically significant effect on the clinical endpoint. All these concepts are discussed in the context of randomized clinical trials in oncology, and illustrated with two meta-analyses in gastric cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Publication bias was not a good reason to discourage trials with low power.

PubMed

Borm, George F; den Heijer, Martin; Zielhuis, Gerhard A

2009-01-01

The objective was to investigate whether it is justified to discourage trials with less than 80% power. Trials with low power are unlikely to produce conclusive results, but their findings can be used by pooling then in a meta-analysis. However, such an analysis may be biased, because trials with low power are likely to have a nonsignificant result and are less likely to be published than trials with a statistically significant outcome. We simulated several series of studies with varying degrees of publication bias and then calculated the "real" one-sided type I error and the bias of meta-analyses with a "nominal" error rate (significance level) of 2.5%. In single trials, in which heterogeneity was set at zero, low, and high, the error rates were 2.3%, 4.7%, and 16.5%, respectively. In multiple trials with 80%-90% power and a publication rate of 90% when the results were nonsignificant, the error rates could be as high as 5.1%. When the power was 50% and the publication rate of non-significant results was 60%, the error rates did not exceed 5.3%, whereas the bias was at most 15% of the difference used in the power calculation. The impact of publication bias does not warrant the exclusion of trials with 50% power.

Duration of treatment for asymptomatic bacteriuria during pregnancy.

PubMed

Villar, J; Lydon-Rochelle, M T; Gülmezoglu, A M; Roganti, A

2000-01-01

A Cochrane systematic review has shown that drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single dose therapy is as effective as longer conventional antibiotic treatment. The objective of this review was to assess the effects of different durations of treatment for asymptomatic bacteriuria in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and the reference lists of articles. Randomised and quasi-randomised trials comparing antimicrobial therapeutic regimens that differed in duration (particularly comparing single dose with longer duration regimens) in pregnant women diagnosed with asymptomatic bacteriuria. Trial quality was assessed and data were extracted independently by the reviewers. Eight studies involving over 400 women were included. All were comparisons of single dose treatment with four to seven day treatments. The trials were generally of poor quality. No difference in 'no-cure' rate was detected between single dose and short course (4-7 day) treatment for asymptomatic bacteriuria in pregnant women (relative risk 1.13, 95% confidence interval 0.82 to 1.54) as well as in the recurrent asymptomtic bacteriuria (relative risk 1.08, 95% confidence interval 0.70 to 1.66). However these results showed significant heterogeneity. No differences were detected for preterm births and pyelonephritis although sample size of trials was small. Longer duration treatment was associated with an increase in reports of adverse effects (relative risk 0.53, 95% confidence interval 0.31 to 0.91). There is not enough evidence to evaluate whether single dose or longer duration doses are more effective in treating asymptomatic bacteriuria in pregnant women. Because single dose has lower cost and increases compliance, this comparison should be explored in a properly sized randomized controlled trial.

Primaquine or other 8-aminoquinolines for reducing Plasmodium falciparum transmission

PubMed Central

Graves, Patricia M; Choi, Leslie; Gelband, Hellen; Garner, Paul

2018-01-01

Background The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance. This replaced the previous recommendation of 0.75 mg/kg, aiming to reduce haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malarious areas. Whether this approach, and at this dose, is effective in reducing transmission is not clear. Objectives To assess the effects of single dose or short-course PQ (or an alternative 8AQ) alongside treatment for people with P. falciparum malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; and the WHO International Clinical Trials Registry Platform (ICRTP) portal using ‘malaria*', ‘falciparum', ‘primaquine', ‘8-aminoquinoline', and eight 8AQ drug names as search terms. We checked reference lists of included trials, and contacted researchers and organizations. Date of last search: 21 July 2017. Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs in children or adults, adding PQ (or alternative 8AQ) as a single dose or short course alongside treatment for P. falciparum malaria. Data collection and analysis Two authors screened abstracts, applied inclusion criteria, and extracted data. We sought evidence on transmission (community incidence), infectiousness (people infectious and mosquitoes infected), and potential infectiousness (gametocyte measures assessed by microscopy or polymerase chain reaction [PCR]). We grouped trials into artemisinin and non-artemisinin treatments, and stratified by PQ dose (low, 0.2 to 0.25 mg/kg; moderate, 0.4 to 0.5 mg/kg; high, 0.75 mg/kg). We used GRADE, and absolute effects of infectiousness using trial control groups. Main results We included 24 RCTs and one quasi-RCT, comprising 43 arms. Fourteen trials evaluated artemisinin treatments (23 arms), nine trials evaluated non-artemisinin treatments (13 arms), and two trials included both artemisinin and non-artemisinin arms (three and two arms, respectively). Two trial arms used bulaquine. Seven PQ arms used low dose (six with artemisinin), 11 arms used moderate dose (seven with artemisinin), and the remaining arms used high dose. Fifteen trials tested for G6PD status: 11 excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and three included all, irrespective of status. The remaining 10 trials either did not test or did not report on testing. No cluster trials evaluating community effects on malaria transmission met the inclusion criteria. With artemisinin treatment Low dose PQ Infectiousness (participants infectious to mosquitoes) was reduced (day 3 or 4: RR 0.12, 95% CI 0.02 to 0.88, 3 trials, 105 participants; day 8: RR 0.34, 95% CI 0.07 to 1.58, 4 trials, 243 participants; low certainty evidence). This translates to a reduction in percentage of people infectious on day 3 or 4 from 14% to 2%, and, for day 8, from 4% to 1%; the waning infectiousness in the control group by day 8 making the absolute effect smaller by day 8. For gametocytes detected by PCR, there was little or no effect of PQ at day 3 or 4 (RR 1.02, 95% CI 0.87 to 1.21; 3 trials, 414 participants; moderate certainty evidence); with reduction at day 8 (RR 0.52, 95% CI 0.41 to 0.65; 4 trials, 532 participants; high certainty evidence). Severe haemolysis was infrequent, with or without PQ, in these groups with few G6PD-deficient individuals (RR 0.98, 95% CI 0.69 to 1.39; 4 trials, 752 participants, moderate certainty evidence). Moderate dose PQ Infectiousness was reduced (day 3 or 4: RR 0.13, 95% CI 0.02 to 0.94; 3 trials, 109 participants; day 8 RR 0.33, 95% CI 0.07 to 1.57; 4 trials, 246 participants; low certainty evidence). Illustrative risk estimates for moderate dose were the same as low dose. The pattern and level of certainty of evidence with gametocytes detected by PCR was the same as low dose, and severe haemolysis was infrequent in both groups. High dose PQ Infectiousness was reduced (day 4: RR 0.2, 95% CI 0.02 to 1.68, 1 trial, 101 participants; day 8: RR 0.18, 95% CI 0.02 to 1.41, 2 trials, 181 participants, low certainty evidence). The effects on gametocyte prevalence showed a similar pattern to moderate and low dose PQ. Trials did not systematically report evidence of haemolysis. With non-artemisinin treatment Trials with non-artemisinin treatment have been conducted only for moderate and high dose PQ. With high dose, infectiousness appeared markedly reduced on day 5 (RR 0.09, 95% CI 0.01 to 0.62; 30 participants, very low certainty evidence), with similar reductions at day 8. For both moderate dose (two trials with 221 people) and high dose (two trials with 30 people), reduction in gametocytes (detected by microscopy) showed similar patterns as for artemisinin treatments, with little or no effect at day 4 or 5, and larger effects by day 8. No trials with non-artemisinin partner drugs systematically sought evidence of severe haemolysis. Two trials comparing bulaquine with PQ suggest bulaquine may have larger effects on gametocytes by microscopy on day 8 (RR 0.41, 95% CI 0.26 to 0.66; 2 trials, 112 participants). Authors' conclusions A single low dose of PQ (0.25 mg/kg) added to artemisinin-based combination therapy for malaria reduces infectiousness of people to mosquitoes at day 3-4 and day 8, and appears as effective as higher doses. The absolute effect is greater at day 3 or 4, and smaller at day 8, in part because of the lower infectiousness in the control group. There was no evidence of increased haemolysis at 0.25 mg/kg, but few G6PD-deficient individuals were included in the trials. The effect on infectiousness precedes the effect of PQ on gametocyte prevalence. We do not know whether single dose PQ could reduce malaria transmission at community level. What is the aim of this review? To assess the effects of adding a single dose of primaquine (PQ) to treatment for falciparum malaria to reduce disease transmission. This Cochrane Review update includes 25 controlled trials. The date of latest search was 21 July 2017. Key messages A single low dose of PQ, at 0.25 mg/kg, which the World Health Organization (WHO) recommends adding to artemisinin-based combination therapy for malaria, reduces infectiousness (transmission from people to mosquitoes). In the trials, the percentage of people who infected mosquitoes three to four days after treatment was reduced from 14% to 2%, with a smaller effect at day 8, from 4% to 1%, with no evidence of harm. What was studied in the review PQ kills gametocytes (malaria transmission stages) of the falciparum malaria parasite. Gametocytes infect mosquitoes during a bite, thus perpetuating transmission. There is concern that PQ may cause red blood cells to burst (haemolysis) in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetically-determined condition common in many malaria-endemic settings, which can lead to anaemia. Recognizing concerns about the risk of haemolysis, the WHO reduced the recommended PQ dose from 0.75 mg/kg to 0.25 mg/kg in 2012. Ideally, this approach would be tested by randomly assigning villages to standard malaria treatment, or standard treatment plus a low dose of PQ, then measuring the effect on malaria over time but this would be difficult and expensive. So, indirect indicators are used to shed light on effectiveness, including feeding studies, in which mosquitoes are allowed to feed on people (or their blood), comparing those who were assigned PQ with those who were not. Alternatively, researchers may simply monitor the presence (prevalence), number (density), and duration (time of persistence) of gametocytes in the blood of people after different treatments, assuming that gametocytes are viable irrespective of exposure to PQ. What the research says The 25 included trials span several decades and include a variety of treatments and PQ doses. Related to safety assessment, some trials tested participants for G6PD activity. Other trials reported results based on their G6PD status, others did not test (or did not say whether they did), and others tested and excluded people with G6PD deficiency. There were no ideal community-level studies that would answer the question directly. Five feeding trials with multiple arms included three low-dose, three medium-dose, and two high-dose comparisons, showing a markedly reduced proportion of people infectious who received PQ in trials with any events. Two trials using older malaria treatments and high dose PQ had similar results. The other trials focused on indirect measures of potential infectiousness of humans to mosquitoes. In these trials, PQ shortened the period of potential infectiousness, with a lower prevalence and density of gametocytes up to day 8 after treatment. The effect was similar at all PQ dose levels. Few serious haemolytic events occurred in these trials, but PQ did affect non-serious haemoglobin measures, even at low doses. What are the main results of the review? A single low dose of PQ added to an artemisinin regimen for malaria reduces infectiousness to mosquitoes and is relatively safe for most people. PQ at WHO-recommended dose reduces infectiousness to mosquitoes on day 3-4 and day 8 with no evidence of harm. It is unclear whether this reduction would materially reduce malaria transmission in communities. PMID:29393511

Design Features of the Diabetes and Periodontal Therapy Trial (DPTT): A Multicenter Randomized Single-Masked Clinical Trial Testing the Effect of Non-surgical Periodontal Therapy on Glycosylated Hemoglobin (HbA1c) Levels in Subjects with Type 2 Diabetes and Chronic Periodontitis

PubMed Central

2013-01-01

Background Evidence suggests that periodontitis is associated with prevalent and incident type 2 diabetes mellitus (T2DM), raising the question of whether periodontitis treatment may improve glycemic control in patients with T2DM. Meta-analyses of mostly small clinical trials suggest that periodontitis treatment results in a modest reduction in glycosylated hemoglobin (Hb) A1c. Purpose The purpose of the Diabetes and Periodontal Therapy Trial (DPTT) was to determine if periodontal treatment reduces HbA1c in patients with T2DM and periodontitis. Methods DPTT was a phase-III, single-masked, multi-center, randomized trial with a planned enrollment of 600 participants. Participants were randomly assigned to receive periodontal treatment immediately (Treatment Group) or after 6 months (Control Group). HbA1c values and clinical periodontal measures were determined at baseline and 3 and 6 months following randomization. Medication usage and dosing were assessed at each visit. Periodontal treatment consisted of scaling and root planing for a minimum of two 90-minute sessions, plus the use of an antibacterial mouth rinse for at least 32 days afterwards. The primary outcome was change in HbA1c from baseline to 6 months and the trial was powered to detect a between-group difference of 0.6%. Secondary outcomes included changes in periodontal clinical measures, fasting plasma glucose, the Homeostasis Model Assessment (HOMA2) and the need for rescue diabetes or periodontal therapy. Conclusion Dental and medical researchers collaborated to recruit, treat and monitor participants with two chronic diseases to determine if treatment of one condition affects the status of the other. PMID:24080100

Bayesian enhancement two-stage design for single-arm phase II clinical trials with binary and time-to-event endpoints.

PubMed

Shi, Haolun; Yin, Guosheng

2018-02-21

Simon's two-stage design is one of the most commonly used methods in phase II clinical trials with binary endpoints. The design tests the null hypothesis that the response rate is less than an uninteresting level, versus the alternative hypothesis that the response rate is greater than a desirable target level. From a Bayesian perspective, we compute the posterior probabilities of the null and alternative hypotheses given that a promising result is declared in Simon's design. Our study reveals that because the frequentist hypothesis testing framework places its focus on the null hypothesis, a potentially efficacious treatment identified by rejecting the null under Simon's design could have only less than 10% posterior probability of attaining the desirable target level. Due to the indifference region between the null and alternative, rejecting the null does not necessarily mean that the drug achieves the desirable response level. To clarify such ambiguity, we propose a Bayesian enhancement two-stage (BET) design, which guarantees a high posterior probability of the response rate reaching the target level, while allowing for early termination and sample size saving in case that the drug's response rate is smaller than the clinically uninteresting level. Moreover, the BET design can be naturally adapted to accommodate survival endpoints. We conduct extensive simulation studies to examine the empirical performance of our design and present two trial examples as applications. © 2018, The International Biometric Society.

Systematic review of physiotherapy interventions to improve gross motor capacity and performance in children and adolescents with an acquired brain injury.

PubMed

Baque, Emmah; Sakzewski, Leanne; Barber, Lee; Boyd, Roslyn N

2016-01-01

To systematically review the efficacy of physiotherapy interventions to improve gross motor capacity, performance and societal participation in children aged 5-17 years with an acquired brain injury (ABI). Randomized and non-randomized controlled trials, cohort, case series, case-control and case studies were included and classified according to grades of evidence. Methodological quality of studies was assessed using the Downs and Black (D&B) scale and quantitative data was analysed using effect sizes. Two home-based studies investigated functional strength training (one randomized controlled trial, n = 20, level 2b, D&B = 16/32 and one non-randomized self-control study, n = 19, level 4, D&B = 15/32). Four studies evaluated virtual reality including: one pilot study, n = 50, level 4, D&B = 22/32; one single-subject, non-concurrent, randomized multiple baseline study, n = 3, level 4, D&B = 15/32; one case series study, n = 2, level 4, D&B = 15/32; one case study, n = 1, level 4, D&B = 15/32. Effect sizes for the randomized controlled trial ranged between 0.30-1.29 for the Functional Reach and Timed Up and Go outcome measures. There is preliminary evidence to support the efficacy of physiotherapy interventions to improve gross motor outcomes in children with an ABI. Both functional strength training and virtual-reality based therapy are potential treatment options for clinicians to prescribe in either home or clinical settings.

First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors.

PubMed

Smith, Barry H; Parikh, Tapan; Andrada, Zoe P; Fahey, Thomas J; Berman, Nathaniel; Wiles, Madeline; Nazarian, Angelica; Thomas, Joanne; Arreglado, Anna; Akahoho, Eugene; Wolf, David J; Levine, Daniel M; Parker, Thomas S; Gazda, Lawrence S; Ocean, Allyson J

2016-01-01

Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs) release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D) via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival), which is the secondary objective. Thirty-one patients underwent up to four intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg) via laparoscopy in this single-arm trial (FDA BB-IND 10091; NCT 00283075). Serial physical examinations, laboratory testing, and PET-CT imaging were performed before and three months after each implant. RMBs were well tolerated at both dose levels (mean 660.9 per implant). AEs were (Grade 1/2) with no treatment-related SAEs. The data support the safety of RMB therapy in advanced-malignancy patients, and the preliminary evidence for their potential efficacy is encouraging. A Phase 2 efficacy trial is ongoing.

Analysis and visualization of single-trial event-related potentials

NASA Technical Reports Server (NTRS)

Jung, T. P.; Makeig, S.; Westerfield, M.; Townsend, J.; Courchesne, E.; Sejnowski, T. J.

2001-01-01

In this study, a linear decomposition technique, independent component analysis (ICA), is applied to single-trial multichannel EEG data from event-related potential (ERP) experiments. Spatial filters derived by ICA blindly separate the input data into a sum of temporally independent and spatially fixed components arising from distinct or overlapping brain or extra-brain sources. Both the data and their decomposition are displayed using a new visualization tool, the "ERP image," that can clearly characterize single-trial variations in the amplitudes and latencies of evoked responses, particularly when sorted by a relevant behavioral or physiological variable. These tools were used to analyze data from a visual selective attention experiment on 28 control subjects plus 22 neurological patients whose EEG records were heavily contaminated with blink and other eye-movement artifacts. Results show that ICA can separate artifactual, stimulus-locked, response-locked, and non-event-related background EEG activities into separate components, a taxonomy not obtained from conventional signal averaging approaches. This method allows: (1) removal of pervasive artifacts of all types from single-trial EEG records, (2) identification and segregation of stimulus- and response-locked EEG components, (3) examination of differences in single-trial responses, and (4) separation of temporally distinct but spatially overlapping EEG oscillatory activities with distinct relationships to task events. The proposed methods also allow the interaction between ERPs and the ongoing EEG to be investigated directly. We studied the between-subject component stability of ICA decomposition of single-trial EEG epochs by clustering components with similar scalp maps and activation power spectra. Components accounting for blinks, eye movements, temporal muscle activity, event-related potentials, and event-modulated alpha activities were largely replicated across subjects. Applying ICA and ERP image visualization to the analysis of sets of single trials from event-related EEG (or MEG) experiments can increase the information available from ERP (or ERF) data. Copyright 2001 Wiley-Liss, Inc.

Single-visit or multiple-visit root canal treatment: systematic review, meta-analysis and trial sequential analysis

PubMed Central

Schwendicke, Falk; Göstemeyer, Gerd

2017-01-01

Objectives Single-visit root canal treatment has some advantages over conventional multivisit treatment, but might increase the risk of complications. We systematically evaluated the risk of complications after single-visit or multiple-visit root canal treatment using meta-analysis and trial-sequential analysis. Data Controlled trials comparing single-visit versus multiple-visit root canal treatment of permanent teeth were included. Trials needed to assess the risk of long-term complications (pain, infection, new/persisting/increasing periapical lesions ≥1 year after treatment), short-term pain or flare-up (acute exacerbation of initiation or continuation of root canal treatment). Sources Electronic databases (PubMed, EMBASE, Cochrane Central) were screened, random-effects meta-analyses performed and trial-sequential analysis used to control for risk of random errors. Evidence was graded according to GRADE. Study selection 29 trials (4341 patients) were included, all but 6 showing high risk of bias. Based on 10 trials (1257 teeth), risk of complications was not significantly different in single-visit versus multiple-visit treatment (risk ratio (RR) 1.00 (95% CI 0.75 to 1.35); weak evidence). Based on 20 studies (3008 teeth), risk of pain did not significantly differ between treatments (RR 0.99 (95% CI 0.76 to 1.30); moderate evidence). Risk of flare-up was recorded by 8 studies (1110 teeth) and was significantly higher after single-visit versus multiple-visit treatment (RR 2.13 (95% CI 1.16 to 3.89); very weak evidence). Trial-sequential analysis revealed that firm evidence for benefit, harm or futility was not reached for any of the outcomes. Conclusions There is insufficient evidence to rule out whether important differences between both strategies exist. Clinical significance Dentists can provide root canal treatment in 1 or multiple visits. Given the possibly increased risk of flare-ups, multiple-visit treatment might be preferred for certain teeth (eg, those with periapical lesions). PMID:28148534

Duration of treatment for asymptomatic bacteriuria during pregnancy.

PubMed

Widmer, Mariana; Gülmezoglu, A Metin; Mignini, Luciano; Roganti, Ariel

2011-12-07

A Cochrane systematic review has shown that drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single-dose therapy is as effective as longer conventional antibiotic treatment. To assess the effects of different durations of treatment for asymptomatic bacteriuria in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2011) and reference lists of identified articles. Randomized and quasi-randomized trials comparing antimicrobial therapeutic regimens that differed in duration (particularly comparing single dose with longer duration regimens) in pregnant women diagnosed with asymptomatic bacteriuria. We assessed trial quality and extracted data independently. We included 13 studies, involving 1622 women. All were comparisons of single-dose treatment with four- to seven-day treatments. The trials were generally of limited quality. The 'no cure rate' for asymptomatic bacteriuria in pregnant women was slightly higher for the single-dose than for the short-course treatment; however, these results were not statistically significant and showed heterogeneity. When comparing the trials that used the same antibiotic in both treatment and control groups with the trials that used different antibiotics in both groups, the 'no cure rate' risk ratio was similar. There was no statistically significant difference in the recurrence of asymptomatic bacteriuria rate between treatment and control groups. Slight differences were detected for preterm births and pyelonephritis although, apart from one trial, the sample size of the trials was inadequate. Single-dose treatment was associated with a decrease in reports of 'any side-effects' . Single-dose regimen of antibiotics may be less effective than the seven-day regimen. Women with asymptomatic bacteriuria in pregnancy should be treated by the standard regimen of antibiotics until more data become available testing seven-day compared with three- or five-day regimens.

Bayesian Dose-Response Modeling in Sparse Data

NASA Astrophysics Data System (ADS)

Kim, Steven B.

This book discusses Bayesian dose-response modeling in small samples applied to two different settings. The first setting is early phase clinical trials, and the second setting is toxicology studies in cancer risk assessment. In early phase clinical trials, experimental units are humans who are actual patients. Prior to a clinical trial, opinions from multiple subject area experts are generally more informative than the opinion of a single expert, but we may face a dilemma when they have disagreeing prior opinions. In this regard, we consider compromising the disagreement and compare two different approaches for making a decision. In addition to combining multiple opinions, we also address balancing two levels of ethics in early phase clinical trials. The first level is individual-level ethics which reflects the perspective of trial participants. The second level is population-level ethics which reflects the perspective of future patients. We extensively compare two existing statistical methods which focus on each perspective and propose a new method which balances the two conflicting perspectives. In toxicology studies, experimental units are living animals. Here we focus on a potential non-monotonic dose-response relationship which is known as hormesis. Briefly, hormesis is a phenomenon which can be characterized by a beneficial effect at low doses and a harmful effect at high doses. In cancer risk assessments, the estimation of a parameter, which is known as a benchmark dose, can be highly sensitive to a class of assumptions, monotonicity or hormesis. In this regard, we propose a robust approach which considers both monotonicity and hormesis as a possibility. In addition, We discuss statistical hypothesis testing for hormesis and consider various experimental designs for detecting hormesis based on Bayesian decision theory. Past experiments have not been optimally designed for testing for hormesis, and some Bayesian optimal designs may not be optimal under a wrong parametric assumption. In this regard, we consider a robust experimental design which does not require any parametric assumption.

Comparison between single-diode low-level laser therapy (LLLT) and LED multi-diode (cluster) therapy (LEDT) applications before high-intensity exercise.

PubMed

Leal Junior, Ernesto Cesar Pinto; Lopes-Martins, Rodrigo Alvaro Brandão; Baroni, Bruno Manfredini; De Marchi, Thiago; Rossi, Rafael Paolo; Grosselli, Douglas; Generosi, Rafael Abeche; de Godoi, Vanessa; Basso, Maira; Mancalossi, José Luis; Bjordal, Jan Magnus

2009-08-01

There is anecdotal evidence that low-level laser therapy (LLLT) may affect the development of muscular fatigue, minor muscle damage, and recovery after heavy exercises. Although manufacturers claim that cluster probes (LEDT) maybe more effective than single-diode lasers in clinical settings, there is a lack of head-to-head comparisons in controlled trials. This study was designed to compare the effect of single-diode LLLT and cluster LEDT before heavy exercise. This was a randomized, placebo-controlled, double-blind cross-over study. Young male volleyball players (n = 8) were enrolled and asked to perform three Wingate cycle tests after 4 x 30 sec LLLT or LEDT pretreatment of the rectus femoris muscle with either (1) an active LEDT cluster-probe (660/850 nm, 10/30 mW), (2) a placebo cluster-probe with no output, and (3) a single-diode 810-nm 200-mW laser. The active LEDT group had significantly decreased post-exercise creatine kinase (CK) levels (-18.88 +/- 41.48 U/L), compared to the placebo cluster group (26.88 +/- 15.18 U/L) (p < 0.05) and the active single-diode laser group (43.38 +/- 32.90 U/L) (p < 0.01). None of the pre-exercise LLLT or LEDT protocols enhanced performance on the Wingate tests or reduced post-exercise blood lactate levels. However, a non-significant tendency toward lower post-exercise blood lactate levels in the treated groups should be explored further. In this experimental set-up, only the active LEDT probe decreased post-exercise CK levels after the Wingate cycle test. Neither performance nor blood lactate levels were significantly affected by this protocol of pre-exercise LEDT or LLLT.

Adherence in single-parent households in a long-term asthma clinical trial.

PubMed

Spicher, Mary; Bollers, Nancy; Chinn, Tamara; Hall, Anita; Plunkett, Anne; Rodgers, Denise; Sundström, D A; Wilson, Laura

2012-01-01

Adherence of participants in a long-term clinical trial is necessary to assure validity of findings. This article examines adherence differences between single-parent and two-parent families in the Childhood Asthma Management Program (CAMP). Adherence was defined as the percentage of completed daily diary cards and scheduled study visits during the course of the trial. Logistic regression and ordinal logistic regression analyses were used. Children from single-parent families had a lower percentage of completed diary cards (72% vs. 84%) than two-parent families. Single-parent families were also more likely to reschedule visits (62% vs. 45%) and miss more clinic visits (23% vs. 17%) than two-parent families. Suggestions are given for study coordinators to assist participants in completing a long-term clinical trial. Many suggestions may be adapted for nurses in inpatient or outpatient settings for assisting parents of patients with chronic diseases.

Measuring and modeling the interaction among reward size, delay to reward, and satiation level on motivation in monkeys.

PubMed

Minamimoto, Takafumi; La Camera, Giancarlo; Richmond, Barry J

2009-01-01

Motivation is usually inferred from the likelihood or the intensity with which behavior is carried out. It is sensitive to external factors (e.g., the identity, amount, and timing of a rewarding outcome) and internal factors (e.g., hunger or thirst). We trained macaque monkeys to perform a nonchoice instrumental task (a sequential red-green color discrimination) while manipulating two external factors: reward size and delay-to-reward. We also inferred the state of one internal factor, level of satiation, by monitoring the accumulated reward. A visual cue indicated the forthcoming reward size and delay-to-reward in each trial. The fraction of trials completed correctly by the monkeys increased linearly with reward size and was hyperbolically discounted by delay-to-reward duration, relations that are similar to those found in free operant and choice tasks. The fraction of correct trials also decreased progressively as a function of the satiation level. Similar (albeit noiser) relations were obtained for reaction times. The combined effect of reward size, delay-to-reward, and satiation level on the proportion of correct trials is well described as a multiplication of the effects of the single factors when each factor is examined alone. These results provide a quantitative account of the interaction of external and internal factors on instrumental behavior, and allow us to extend the concept of subjective value of a rewarding outcome, usually confined to external factors, to account also for slow changes in the internal drive of the subject.

Measuring and Modeling the Interaction Among Reward Size, Delay to Reward, and Satiation Level on Motivation in Monkeys

PubMed Central

Minamimoto, Takafumi; La Camera, Giancarlo; Richmond, Barry J.

2009-01-01

Motivation is usually inferred from the likelihood or the intensity with which behavior is carried out. It is sensitive to external factors (e.g., the identity, amount, and timing of a rewarding outcome) and internal factors (e.g., hunger or thirst). We trained macaque monkeys to perform a nonchoice instrumental task (a sequential red-green color discrimination) while manipulating two external factors: reward size and delay-to-reward. We also inferred the state of one internal factor, level of satiation, by monitoring the accumulated reward. A visual cue indicated the forthcoming reward size and delay-to-reward in each trial. The fraction of trials completed correctly by the monkeys increased linearly with reward size and was hyperbolically discounted by delay-to-reward duration, relations that are similar to those found in free operant and choice tasks. The fraction of correct trials also decreased progressively as a function of the satiation level. Similar (albeit noiser) relations were obtained for reaction times. The combined effect of reward size, delay-to-reward, and satiation level on the proportion of correct trials is well described as a multiplication of the effects of the single factors when each factor is examined alone. These results provide a quantitative account of the interaction of external and internal factors on instrumental behavior, and allow us to extend the concept of subjective value of a rewarding outcome, usually confined to external factors, to account also for slow changes in the internal drive of the subject. PMID:18987119

Rehabilitation after anterior cruciate ligament reconstruction: a systematic review.

PubMed

Kruse, L M; Gray, B; Wright, R W

2012-10-03

Rigorous rehabilitation after anterior cruciate ligament (ACL) reconstruction is necessary for a successful surgical outcome. A large number of clinical trials continue to assess aspects of this rehabilitation process. Prior systematic reviews evaluated fifty-four Level-I and II clinical trials published through 2005. Eighty-five articles from 2006 to 2010 were identified utilizing multiple search engines. Twenty-nine Level-I or II studies met inclusion criteria and were evaluated with use of the CONSORT (Consolidated Standards of Reporting Trials) criteria. Topics included in this review are postoperative bracing, accelerated strengthening, home-based rehabilitation, proprioception and neuromuscular training, and six miscellaneous topics investigated in single trials. Bracing following ACL reconstruction remains neither necessary nor beneficial and adds to the cost of the procedure. Early return to sports needs further research. Home-based rehabilitation can be successful. Although neuromuscular interventions are not likely to be harmful to patients, they are also not likely to yield large improvements in outcomes or help patients return to sports faster. Thus, they should not be performed to the exclusion of strengthening and range-of-motion exercises. Vibration training may lead to faster and more complete proprioceptive recovery but further evidence is needed. Several new modalities for rehabilitation after ACL reconstruction may be helpful but should not be performed to the exclusion of range-of-motion, strengthening, and functional exercises. Accelerated rehabilitation does not appear to be harmful but further investigation of rehabilitation timing is warranted. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Evaluation of a toxoid for protection of rabbits against enterotoxaemia experimentally induced by trypsin-activated supernatant of Clostridium spiroforme.

PubMed

Ellis, T M; Gregory, A R; Logue, G D

1991-06-01

Investigations were conducted into an enterotoxaemia caused by Clostridium spiroforme responsible for significant losses in commercial rabbit farms in Western Australia. Two trials using laboratory and farm bred rabbits were performed to evaluate the protective value of a toxoid prepared from the supernatant of C. spiroforme cultures against intraperitoneal challenge with the trypsin-activated toxin of C. spiroforme. The trials showed clearly that a single vaccination at weaning (four weeks) was protective against toxin but more complete and lasting protection was conferred following a second vaccination administered 14 days after the first. Adults likewise showed similar levels of protective antibodies but did not appear to pass on this protection to their kits although ELISA results indicated levels of antibody in kits from unvaccinated mother to be lower than progeny from vaccinated mothers. However antibody levels in kits from vaccinated mothers were very low and did not protect against challenge with toxin.

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

PubMed Central

2013-01-01

Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

Rationale and design of the Study of a Tele-pharmacy Intervention for Chronic diseases to Improve Treatment adherence (STIC2IT): A cluster-randomized pragmatic trial.

PubMed

Choudhry, Niteesh K; Isaac, Thomas; Lauffenburger, Julie C; Gopalakrishnan, Chandrasekar; Khan, Nazleen F; Lee, Marianne; Vachon, Amy; Iliadis, Tanya L; Hollands, Whitney; Doheny, Scott; Elman, Sandra; Kraft, Jacqueline M; Naseem, Samrah; Gagne, Joshua J; Jackevicius, Cynthia A; Fischer, Michael A; Solomon, Daniel H; Sequist, Thomas D

2016-10-01

Approximately half of patients with chronic cardiometabolic conditions are nonadherent with their prescribed medications. Interventions to improve adherence have been only modestly effective because they often address single barriers to adherence, intervene at single points in time, or are imprecisely targeted to patients who may not need adherence assistance. To evaluate the effect of a multicomponent, behaviorally tailored pharmacist-based intervention to improve adherence to medications for diabetes, hypertension, and hyperlipidemia. The STIC2IT trial is a cluster-randomized pragmatic trial testing the impact of a pharmacist-led multicomponent intervention that uses behavioral interviewing, text messaging, mailed progress reports, and video visits. Targeted patients are those who are nonadherent to glucose-lowering, antihypertensive, or statin medications and who also have evidence of poor disease control. The intervention is tailored to patients' individual health barriers and their level of health activation. We cluster-randomized 14 practice sites of a large multispecialty group practice to receive either the pharmacist-based intervention or usual care. STIC2IT has enrolled 4,076 patients who will be followed up for 12months after randomization. The trial's primary outcome is medication adherence, assessed using pharmacy claims data. Secondary outcomes are disease control and health care resource utilization. This trial will determine whether a technologically enabled, behaviorally targeted pharmacist-based intervention results in improved adherence and disease control. If effective, this strategy could be a scalable method of offering tailored adherence support to those with the greatest clinical need. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrating the behavioral and neural dynamics of response selection in a dual-task paradigm: a dynamic neural field model of Dux et al. (2009).

PubMed

Buss, Aaron T; Wifall, Tim; Hazeltine, Eliot; Spencer, John P

2014-02-01

People are typically slower when executing two tasks than when only performing a single task. These dual-task costs are initially robust but are reduced with practice. Dux et al. (2009) explored the neural basis of dual-task costs and learning using fMRI. Inferior frontal junction (IFJ) showed a larger hemodynamic response on dual-task trials compared with single-task trial early in learning. As dual-task costs were eliminated, dual-task hemodynamics in IFJ reduced to single-task levels. Dux and colleagues concluded that the reduction of dual-task costs is accomplished through increased efficiency of information processing in IFJ. We present a dynamic field theory of response selection that addresses two questions regarding these results. First, what mechanism leads to the reduction of dual-task costs and associated changes in hemodynamics? We show that a simple Hebbian learning mechanism is able to capture the quantitative details of learning at both the behavioral and neural levels. Second, is efficiency isolated to cognitive control areas such as IFJ, or is it also evident in sensory motor areas? To investigate this, we restrict Hebbian learning to different parts of the neural model. None of the restricted learning models showed the same reductions in dual-task costs as the unrestricted learning model, suggesting that efficiency is distributed across cognitive control and sensory motor processing systems.

The effect of an interactive cycling training on cognitive functioning in older adults with mild dementia: study protocol for a randomized controlled trial.

PubMed

Karssemeijer, E G A; Bossers, W J R; Aaronson, J A; Kessels, R P C; Olde Rikkert, M G M

2017-03-21

To date there is no cure or an effective disease-modifying drug to treat dementia. Available acetylcholine-esterase inhibiting drugs or memantine only produce small benefits on cognitive and behavioural functioning and their clinical relevance remains controversial. Combined cognitive-aerobic interventions are an appealing alternative or add-on to current pharmacological treatments. The primary aim of this study is to investigate the efficacy of a combined cognitive-aerobic training and a single aerobic training compared to an active control group in older adults with mild dementia. We expect to find a beneficial effect on executive functioning in both training regimes, compared to the control intervention, with the largest effect in the combined cognitive-aerobic group. Secondary, intervention effects on cognitive functioning in other domains, physical functioning, physical activity levels, activities of daily living, frailty and quality of life are studied. The design is a single-blind, randomized controlled trial (RCT) with three groups: a combined cognitive-aerobic bicycle training (interactive cycling), a single aerobic bicycle training and a control intervention, which consists of stretching and toning exercises. Older adults with mild dementia follow a 12-week training program consisting of three training sessions of 30-40 min per week. The primary study outcome is objective executive functioning measured with a neuropsychological assessment. Secondary measures are objective cognitive functioning in other domains, physical functioning, physical activity levels, activities of daily living, frailty, mood and quality of life. The three groups are compared at baseline, after 6 and 12 weeks of training, and at 24-week follow-up. This study will provide novel information on the effects of an interactive cycling training on executive function in older adults with mild dementia. Furthermore, since this study has both a combined cognitive-aerobic training and a single aerobic training group the effectiveness of the different components of the intervention can be identified. The results of this study may be used for physical and mental activity recommendations in older adults with dementia. The Netherlands National Trial Register NTR5581 . Registered 14 February 2016.

A Bayesian approach for incorporating economic factors in sample size design for clinical trials of individual drugs and portfolios of drugs.

PubMed

Patel, Nitin R; Ankolekar, Suresh

2007-11-30

Classical approaches to clinical trial design ignore economic factors that determine economic viability of a new drug. We address the choice of sample size in Phase III trials as a decision theory problem using a hybrid approach that takes a Bayesian view from the perspective of a drug company and a classical Neyman-Pearson view from the perspective of regulatory authorities. We incorporate relevant economic factors in the analysis to determine the optimal sample size to maximize the expected profit for the company. We extend the analysis to account for risk by using a 'satisficing' objective function that maximizes the chance of meeting a management-specified target level of profit. We extend the models for single drugs to a portfolio of clinical trials and optimize the sample sizes to maximize the expected profit subject to budget constraints. Further, we address the portfolio risk and optimize the sample sizes to maximize the probability of achieving a given target of expected profit.

Preemptive use of etodolac on tooth sensitivity after in-office bleaching: a randomized clinical trial

PubMed Central

Vaez, Savil Costa; Faria-e-Silva, André Luís; Loguércio, Alessandro Dourado; Fernandes, Micaelle Tenório Guedes; Nahsan, Flávia Pardo Salata

2018-01-01

Abstract Purpose This study determined the effectiveness of the preemptive administration of etodolac on risk and intensity of tooth sensitivity and the bleaching effect caused by in-office bleaching using 35% hydrogen peroxide. Material and methods Fifty patients were selected for this tripleblind, randomized, crossover, and placebo-controlled clinical trial. Etodolac (400 mg) or placebo was administrated in a single-dose 1 hour prior to the bleaching procedure. The whitening treatment with 35% hydrogen peroxide was carried out in two sessions with a 7-day interval. Tooth sensitivity was assessed before, during, and 24 hours after the procedure using the analog visual scale and the verbal rating scale. Color alteration was assessed by a bleach guide scale, 7 days after each session. Relative risk of sensitivity was calculated and adjusted by session, while overall risk was compared by the McNemar's test. Data on the sensitivity level of both scales and color shade were subjected to Friedman, Wilcoxon, and Mann-Whitney tests, respectively (α=0.05). Results The preemptive administration of etodolac did not affect the risk of tooth sensitivity and the level of sensitivity reported, regardless of the time of evaluation and scale used. The sequence of treatment allocation did not affect bleaching effectiveness, while the second session resulted in additional color modification. The preemptive administration of etodolac in a single dose 1 hour prior to in-office tooth bleaching did not alter tooth color, and the risk and intensity of tooth sensitivity reported by patients. Conclusion A single-dose preemptive administration of 400 mg of etodolac did not affect either risk of tooth sensitivity or level of sensitivity reported by patients, during or after the in-office tooth bleaching procedure. PMID:29412363

Preemptive use of etodolac on tooth sensitivity after in-office bleaching: a randomized clinical trial.

PubMed

Vaez, Savil Costa; Faria-E-Silva, André Luís; Loguércio, Alessandro Dourado; Fernandes, Micaelle Tenório Guedes; Nahsan, Flávia Pardo Salata

2018-02-01

This study determined the effectiveness of the preemptive administration of etodolac on risk and intensity of tooth sensitivity and the bleaching effect caused by in-office bleaching using 35% hydrogen peroxide. Fifty patients were selected for this tripleblind, randomized, crossover, and placebo-controlled clinical trial. Etodolac (400 mg) or placebo was administrated in a single-dose 1 hour prior to the bleaching procedure. The whitening treatment with 35% hydrogen peroxide was carried out in two sessions with a 7-day interval. Tooth sensitivity was assessed before, during, and 24 hours after the procedure using the analog visual scale and the verbal rating scale. Color alteration was assessed by a bleach guide scale, 7 days after each session. Relative risk of sensitivity was calculated and adjusted by session, while overall risk was compared by the McNemar's test. Data on the sensitivity level of both scales and color shade were subjected to Friedman, Wilcoxon, and Mann-Whitney tests, respectively (α=0.05). The preemptive administration of etodolac did not affect the risk of tooth sensitivity and the level of sensitivity reported, regardless of the time of evaluation and scale used. The sequence of treatment allocation did not affect bleaching effectiveness, while the second session resulted in additional color modification. The preemptive administration of etodolac in a single dose 1 hour prior to in-office tooth bleaching did not alter tooth color, and the risk and intensity of tooth sensitivity reported by patients. A single-dose preemptive administration of 400 mg of etodolac did not affect either risk of tooth sensitivity or level of sensitivity reported by patients, during or after the in-office tooth bleaching procedure.

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review.

PubMed

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010-2015). All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Quality of reporting was assessed using the Key Methodological Score. 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles.

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review

PubMed Central

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Background Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. Data sources A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010–2015). Study eligibility criteria All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Intervention Quality of reporting was assessed using the Key Methodological Score. Results 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Limitations Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. Conclusions & implications of key findings This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles. PMID:29216190

Selectivity of N170 for visual words in the right hemisphere: Evidence from single-trial analysis.

PubMed

Yang, Hang; Zhao, Jing; Gaspar, Carl M; Chen, Wei; Tan, Yufei; Weng, Xuchu

2017-08-01

Neuroimaging and neuropsychological studies have identified the involvement of the right posterior region in the processing of visual words. Interestingly, in contrast, ERP studies of the N170 typically demonstrate selectivity for words more strikingly over the left hemisphere. Why is right hemisphere selectivity for words during the N170 epoch typically not observed, despite the clear involvement of this region in word processing? One possibility is that amplitude differences measured on averaged ERPs in previous studies may have been obscured by variation in peak latency across trials. This study examined this possibility by using single-trial analysis. Results show that words evoked greater single-trial N170s than control stimuli in the right hemisphere. Additionally, we observed larger trial-to-trial variability on N170 peak latency for words as compared to control stimuli over the right hemisphere. Results demonstrate that, in contrast to much of the prior literature, the N170 can be selective to words over the right hemisphere. This discrepancy is explained in terms of variability in trial-to-trial peak latency for responses to words over the right hemisphere. © 2017 Society for Psychophysiological Research.

ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for a single-arm feasibility trial.

PubMed

China, Louise; Muirhead, Nicola; Skene, Simon S; Shabir, Zainib; De Maeyer, Roel P H; Maini, Alexander A N; Gilroy, Derek W; O'Brien, Alastair J

2016-01-25

Circulating prostaglandin E2 levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds and inactivates this hormone. Human albumin solution could thus be repurposed as an immune restorative drug in these patients.This feasibility study aims to determine whether it is possible and safe to restore serum albumin to >30 g/L and maintain it at this level in patients admitted with acute decompensated cirrhosis using repeated 20% human albumin infusions according to daily serum albumin levels. Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) stage 1 is a multicentre, open label dose feasibility trial. Patients with acutely decompensated cirrhosis admitted to hospital with a serum albumin of <30 g/L are eligible, subject to exclusion criteria. Daily intravenous human albumin solution will be infused, according to serum albumin levels, for up to 14 days or discharge in all patients. The primary end point is daily serum albumin levels for the duration of the treatment period and the secondary end point is plasma-induced macrophage dysfunction. The trial will recruit 80 patients. Outcomes will be used to assist with study design for an 866 patient randomised controlled trial at more than 30 sites across the UK. Research ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001-0001). Will be disseminated through peer reviewed journals and international conferences. Recruitment of the first participant occurred on 26/05/2015. The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the NIHR (ISRCTN 14174793). This manuscript refers to V.4.0 of the protocol; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

PubMed

Liu, Wei; Ding, Jinhui

2018-04-01

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

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

PubMed

Stevanovic, Ana; Coburn, Mark; Menon, Ares; Rossaint, Rolf; Heyland, Daren; Schälte, Gereon; Werker, Thilo; Wonisch, Willibald; Kiehntopf, Michael; Goetzenich, Andreas; Rex, Steffen; Stoppe, Christian

2014-01-01

Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL-6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r =  -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. ClinicalTrials.gov NCT01409057.

A Bayesian Approach to Estimating Coupling Between Neural Components: Evaluation of the Multiple Component, Event-Related Potential (mcERP) Algorithm

NASA Technical Reports Server (NTRS)

Shah, Ankoor S.; Knuth, Kevin H.; Truccolo, Wilson A.; Ding, Ming-Zhou; Bressler, Steven L.; Schroeder, Charles E.; Clancy, Daniel (Technical Monitor)

2002-01-01

Accurate measurement of single-trial responses is key to a definitive use of complex electromagnetic and hemodynamic measurements in the investigation of brain dynamics. We developed the multiple component, Event-Related Potential (mcERP) approach to single-trial response estimation. To improve our resolution of dynamic interactions between neuronal ensembles located in different layers within a cortical region and/or in different cortical regions. The mcERP model assets that multiple components defined as stereotypic waveforms comprise the stimulus-evoked response and that these components may vary in amplitude and latency from trial to trial. Maximum a posteriori (MAP) solutions for the model are obtained by iterating a set of equations derived from the posterior probability. Our first goal was to use the ANTWERP algorithm to analyze interactions (specifically latency and amplitude correlation) between responses in different layers within a cortical region. Thus, we evaluated the model by applying the algorithm to synthetic data containing two correlated local components and one independent far-field component. Three cases were considered: the local components were correlated by an interaction in their single-trial amplitudes, by an interaction in their single-trial latencies, or by an interaction in both amplitude and latency. We then analyzed the accuracy with which the algorithm estimated the component waveshapes and the single-trial parameters as a function of the linearity of each of these relationships. Extensions of these analyses to real data are discussed as well as ongoing work to incorporate more detailed prior information.

Single-use instruments, cutting blocks, and trials increase efficiency in the operating room during total knee arthroplasty: a prospective comparison of navigated and non-navigated cases.

PubMed

Mont, Michael A; McElroy, Mark J; Johnson, Aaron J; Pivec, Robert

2013-08-01

The purpose of this prospective controlled trial was to determine if efficiency increases could be achieved in non-navigated and navigated total knee arthroplasties by replacing traditional saws, cutting blocks, and trials with specialized saws and single-use cutting blocks and trials. Various timing metrics during total knee arthroplasty, including operating room preparation times and specific intra-operative times, were measured in 400 procedures performed by eight different surgeons at 6 institutions. Efficiency increases were the result of statistically significant reductions in combined instrument setup and cleanup times as well as in adjusted surgical episode times in navigated total knee arthroplasties. Single-use instruments show promising benefits, but adequate patient follow-up is needed to confirm safety and efficacy before they can be widely adopted. Nevertheless, the authors believe that the use of single-use instruments, cutting guides, and trial implants for total knee arthroplasty will play an increasing role in improving operating room efficiency. Copyright © 2013 Elsevier Inc. All rights reserved.

A Randomized Cross-Over Trial of the Postprandial Effects of Three Different Diets in Patients with Type 2 Diabetes

PubMed Central

Bunjaku, Bekim; Rosenqvist, Ulf; Nystrom, Fredrik H.; Guldbrand, Hans

2013-01-01

Background In the clinic setting both fasting levels of glucose and the area under the curve (AUC) of glucose, by determination of HbA1c levels, are used for risk assessments, in type 2 diabetes (NIDDM). However little is known about postprandial levels, and hence AUC, regarding other traditional risk factors such as insulin and blood-lipids and how this is affected by different diets. Objective To study postprandial effects of three diets, during a single day, in NIDDM. Methods A low-fat diet (45–56 energy-% from carbohydrates), and a low-carbohydrate diet (16–24 energy-% from carbohydrates) was compared with a Mediterranean-style diet (black coffee for breakfast and the same total-caloric intake as the other two diets for lunch with red wine, 32–35 energy−% from carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day at the clinic from food was 1025–1080 kCal in men and 905–984 kCal in women. The test meals were consumed at a diabetes ward under supervision. Results Twenty-one participants were recruited and 19 completed the studies. The low-carbohydrate diet induced lower insulin and glucose excursions compared with the low-fat diet (p<0.0005 for both AUC). The insulin-response following the single Mediterranean-style lunch-meal was more pronounced than during the low-fat diet lunch (insulin increase-ratio of the low-fat diet: 4.35±2.2, of Mediterranean-style diet: 8.12±5.2, p = 0.001) while postprandial glucose levels were similar. The increase-ratio of insulin correlated with the elevation of the incretin glucose-dependent insulinotropic-polypeptide following the Mediterranean-style diet lunch (Spearman, r = 0.64, p = 0.003). Conclusions The large Mediterranean-style lunch-meal induced similar postprandial glucose-elevations as the low-fat meal despite almost double amount of calories due to a pronounced insulin-increase. This suggests that accumulation of caloric intake from breakfast and lunch to a single large Mediterranean style lunch-meal in NIDDM might be advantageous from a metabolic perspective. Trial Registration ClinicalTrials.gov NCT01522157 NCT01522157 PMID:24312178

Spontaneous Fluctuations in Sensory Processing Predict Within-Subject Reaction Time Variability.

PubMed

Ribeiro, Maria J; Paiva, Joana S; Castelo-Branco, Miguel

2016-01-01

When engaged in a repetitive task our performance fluctuates from trial-to-trial. In particular, inter-trial reaction time variability has been the subject of considerable research. It has been claimed to be a strong biomarker of attention deficits, increases with frontal dysfunction, and predicts age-related cognitive decline. Thus, rather than being just a consequence of noise in the system, it appears to be under the control of a mechanism that breaks down under certain pathological conditions. Although the underlying mechanism is still an open question, consensual hypotheses are emerging regarding the neural correlates of reaction time inter-trial intra-individual variability. Sensory processing, in particular, has been shown to covary with reaction time, yet the spatio-temporal profile of the moment-to-moment variability in sensory processing is still poorly characterized. The goal of this study was to characterize the intra-individual variability in the time course of single-trial visual evoked potentials and its relationship with inter-trial reaction time variability. For this, we chose to take advantage of the high temporal resolution of the electroencephalogram (EEG) acquired while participants were engaged in a 2-choice reaction time task. We studied the link between single trial event-related potentials (ERPs) and reaction time using two different analyses: (1) time point by time point correlation analyses thereby identifying time windows of interest; and (2) correlation analyses between single trial measures of peak latency and amplitude and reaction time. To improve extraction of single trial ERP measures related with activation of the visual cortex, we used an independent component analysis (ICA) procedure. Our ERP analysis revealed a relationship between the N1 visual evoked potential and reaction time. The earliest time point presenting a significant correlation of its respective amplitude with reaction time occurred 175 ms after stimulus onset, just after the onset of the N1 peak. Interestingly, single trial N1 latency correlated significantly with reaction time, while N1 amplitude did not. In conclusion, our findings suggest that inter-trial variability in the timing of extrastriate visual processing contributes to reaction time variability.

Spontaneous Fluctuations in Sensory Processing Predict Within-Subject Reaction Time Variability

PubMed Central

Ribeiro, Maria J.; Paiva, Joana S.; Castelo-Branco, Miguel

2016-01-01

When engaged in a repetitive task our performance fluctuates from trial-to-trial. In particular, inter-trial reaction time variability has been the subject of considerable research. It has been claimed to be a strong biomarker of attention deficits, increases with frontal dysfunction, and predicts age-related cognitive decline. Thus, rather than being just a consequence of noise in the system, it appears to be under the control of a mechanism that breaks down under certain pathological conditions. Although the underlying mechanism is still an open question, consensual hypotheses are emerging regarding the neural correlates of reaction time inter-trial intra-individual variability. Sensory processing, in particular, has been shown to covary with reaction time, yet the spatio-temporal profile of the moment-to-moment variability in sensory processing is still poorly characterized. The goal of this study was to characterize the intra-individual variability in the time course of single-trial visual evoked potentials and its relationship with inter-trial reaction time variability. For this, we chose to take advantage of the high temporal resolution of the electroencephalogram (EEG) acquired while participants were engaged in a 2-choice reaction time task. We studied the link between single trial event-related potentials (ERPs) and reaction time using two different analyses: (1) time point by time point correlation analyses thereby identifying time windows of interest; and (2) correlation analyses between single trial measures of peak latency and amplitude and reaction time. To improve extraction of single trial ERP measures related with activation of the visual cortex, we used an independent component analysis (ICA) procedure. Our ERP analysis revealed a relationship between the N1 visual evoked potential and reaction time. The earliest time point presenting a significant correlation of its respective amplitude with reaction time occurred 175 ms after stimulus onset, just after the onset of the N1 peak. Interestingly, single trial N1 latency correlated significantly with reaction time, while N1 amplitude did not. In conclusion, our findings suggest that inter-trial variability in the timing of extrastriate visual processing contributes to reaction time variability. PMID:27242470

Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis.

PubMed

Bekiari, Eleni; Kitsios, Konstantinos; Thabit, Hood; Tauschmann, Martin; Athanasiadou, Eleni; Karagiannis, Thomas; Haidich, Anna-Bettina; Hovorka, Roman; Tsapas, Apostolos

2018-04-18

To evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes. Systematic review and meta-analysis of randomised controlled trials. Medline, Embase, Cochrane Library, and grey literature up to 2 February 2018. Randomised controlled trials in non-pregnant outpatients with type 1 diabetes that compared the use of any artificial pancreas system with any type of insulin based treatment. Primary outcome was proportion (%) of time that sensor glucose level was within the near normoglycaemic range (3.9-10 mmol/L). Secondary outcomes included proportion (%) of time that sensor glucose level was above 10 mmol/L or below 3.9 mmol/L, low blood glucose index overnight, mean sensor glucose level, total daily insulin needs, and glycated haemoglobin. The Cochrane Collaboration risk of bias tool was used to assess study quality. 40 studies (1027 participants with data for 44 comparisons) were included in the meta-analysis. 35 comparisons assessed a single hormone artificial pancreas system, whereas nine comparisons assessed a dual hormone system. Only nine studies were at low risk of bias. Proportion of time in the near normoglycaemic range (3.9-10.0 mmol/L) was significantly higher with artificial pancreas use, both overnight (weighted mean difference 15.15%, 95% confidence interval 12.21% to 18.09%) and over a 24 hour period (9.62%, 7.54% to 11.7%). Artificial pancreas systems had a favourable effect on the proportion of time with sensor glucose level above 10 mmol/L (-8.52%, -11.14% to -5.9%) or below 3.9 mmol/L (-1.49%, -1.86% to -1.11%) over 24 hours, compared with control treatment. Robustness of findings for the primary outcome was verified in sensitivity analyses, by including only trials at low risk of bias (11.64%, 9.1% to 14.18%) or trials under unsupervised, normal living conditions (10.42%, 8.63% to 12.2%). Results were consistent in a subgroup analysis both for single hormone and dual hormone artificial pancreas systems. Artificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes. The main limitations of current research evidence on artificial pancreas systems are related to inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials. 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.

Ketamine rapidly relieves acute suicidal ideation in cancer patients: a randomized controlled clinical trial.

PubMed

Fan, Wei; Yang, HaiKou; Sun, Yong; Zhang, Jun; Li, Guangming; Zheng, Ying; Liu, Yi

2017-01-10

This study was designed to examine the rapid antidepressant effects of single dose ketamine on suicidal ideation and overall depression level in patients with newly-diagnosed cancer. Forty-two patients were enrolled into the controlled trial and randomized into two groups: ketamine group and midazolam group. Patients from the two groups received a sub-anesthetic dose of racemic ketamine hydrochloride or midazolam. Suicidal ideation score, measured with the Beck Scale and suicidal part of the Montgomery-Asberg Depression Rating Scale, significantly decreased on day 1 and day 3 in ketamine-treated patients when compared to those treated with midazolam. Consistently, overall depression levels measured using the Montgomery-Asberg Depression Rating Scale indicated a significant relief of overall depression on day 1 in ketamine-treated patients. Collectively, this study provides novel information about the rapid antidepressant effect of ketamine on acute depression and suicidal ideation in newly-diagnosed cancer patients.

Patients' preferences for selection of endpoints in cardiovascular clinical trials.

PubMed

Chow, Robert D; Wankhedkar, Kashmira P; Mete, Mihriye

2014-01-01

To reduce the duration and overall costs of cardiovascular trials, use of the combined endpoints in trial design has become commonplace. Though this methodology may serve the needs of investigators and trial sponsors, the preferences of patients or potential trial subjects in the trial design process has not been studied. To determine the preferences of patients in the design of cardiovascular trials. Participants were surveyed in a pilot study regarding preferences among various single endpoints commonly used in cardiovascular trials, preference for single vs. composite endpoints, and the likelihood of compliance with a heart medication if patients similar to them participated in the trial design process. One hundred adult English-speaking patients, 38% male, from a primary care ambulatory practice located in an urban setting. Among single endpoints, participants rated heart attack as significantly more important than death from other causes (4.53 vs. 3.69, p=0.004) on a scale of 1-6. Death from heart disease was rated as significantly more important than chest pain (4.73 vs. 2.47, p<0.001), angioplasty/PCI/CABG (4.73 vs. 2.43, p<0.001), and stroke (4.73 vs. 2.43, p<0.001). Participants also expressed a slight preference for combined endpoints over single endpoint (43% vs. 57%), incorporation of the opinions of the study patient population into the design of trials (48% vs. 41% for researchers), and a greater likelihood of medication compliance if patient preferences were considered during trial design (67% indicated a significant to major effect). Patients are able to make judgments and express preferences regarding trial design. They prefer that the opinions of the study population rather than the general population be incorporated into the design of the study. This novel approach to study design would not only incorporate patient preferences into medical decision making, but it also has the potential to improve compliance with cardiovascular medications.

Single treatments that have lasting effects: some thoughts on the antidepressant effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin

PubMed Central

Young, Simon N.

2013-01-01

Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research with animal models of depression suggesting that glutamate may be involved in depression, the N-methyl-d-aspartate antagonist ketamine has been tested in several trials. A single dose decreased depression for up to a week. The reported effects of the use of mushrooms containing psilocybin by a number of cultures around the world has stimulated several trials showing beneficial effects of a single dose of psilocybin for over a year in healthy people, and for up to 3 months in patients with anxiety disorders who have advanced cancer. This article discusses these studies, their rationale, their possible mechanisms of action, the future clinical research required to establish these therapies and the basic research required to optimize single treatments that have lasting effects. PMID:23171696

Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: Study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Children with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain. Methods/design This study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05. Discussion This clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting. Trial registration Current Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20 PMID:22647439

Vowel Imagery Decoding toward Silent Speech BCI Using Extreme Learning Machine with Electroencephalogram

PubMed Central

Kim, Jongin; Park, Hyeong-jun

2016-01-01

The purpose of this study is to classify EEG data on imagined speech in a single trial. We recorded EEG data while five subjects imagined different vowels, /a/, /e/, /i/, /o/, and /u/. We divided each single trial dataset into thirty segments and extracted features (mean, variance, standard deviation, and skewness) from all segments. To reduce the dimension of the feature vector, we applied a feature selection algorithm based on the sparse regression model. These features were classified using a support vector machine with a radial basis function kernel, an extreme learning machine, and two variants of an extreme learning machine with different kernels. Because each single trial consisted of thirty segments, our algorithm decided the label of the single trial by selecting the most frequent output among the outputs of the thirty segments. As a result, we observed that the extreme learning machine and its variants achieved better classification rates than the support vector machine with a radial basis function kernel and linear discrimination analysis. Thus, our results suggested that EEG responses to imagined speech could be successfully classified in a single trial using an extreme learning machine with a radial basis function and linear kernel. This study with classification of imagined speech might contribute to the development of silent speech BCI systems. PMID:28097128

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

PubMed

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

2016-04-16

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

Introducing the Event Related Fixed Interval Area (ERFIA) Multilevel Technique: a Method to Analyze the Complete Epoch of Event-Related Potentials at Single Trial Level

PubMed Central

Vossen, Catherine J.; Vossen, Helen G. M.; Marcus, Marco A. E.; van Os, Jim; Lousberg, Richel

2013-01-01

In analyzing time-locked event-related potentials (ERPs), many studies have focused on specific peaks and their differences between experimental conditions. In theory, each latency point after a stimulus contains potentially meaningful information, regardless of whether it is peak-related. Based on this assumption, we introduce a new concept which allows for flexible investigation of the whole epoch and does not primarily focus on peaks and their corresponding latencies. For each trial, the entire epoch is partitioned into event-related fixed-interval areas under the curve (ERFIAs). These ERFIAs, obtained at single trial level, act as dependent variables in a multilevel random regression analysis. The ERFIA multilevel method was tested in an existing ERP dataset of 85 healthy subjects, who underwent a rating paradigm of 150 painful and non-painful somatosensory electrical stimuli. We modeled the variability of each consecutive ERFIA with a set of predictor variables among which were stimulus intensity and stimulus number. Furthermore, we corrected for latency variations of the P2 (260 ms). With respect to known relationships between stimulus intensity, habituation, and pain-related somatosensory ERP, the ERFIA method generated highly comparable results to those of commonly used methods. Notably, effects on stimulus intensity and habituation were also observed in non-peak-related latency ranges. Further, cortical processing of actual stimulus intensity depended on the intensity of the previous stimulus, which may reflect pain-memory processing. In conclusion, the ERFIA multilevel method is a promising tool that can be used to study event-related cortical processing. PMID:24224018

Single-dose intra-articular bupivacaine versus morphine after arthroscopic knee surgery: a meta-analysis of randomized-controlled studies.

PubMed

Wei, Jie; Lei, Guang-hua; Gao, Shu-Guang; Zeng, Chao; Qin, Jia-bi; Kong, Fan-jing; Yang, Tu-bao

2014-07-01

This meta-analysis compared the earliest clinical effects of intra-articular bupivacaine and morphine for pain management following arthroscopic knee surgery. A comprehensive literature search was conducted using MEDLINE (1966 to 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Google Scholar databases for identification of randomized-controlled trials that compared IA bupivacaine and morphine for postoperative pain. The relative risk, weighted mean difference (WMD), and their corresponding 95% confidence intervals (CI) were calculated using RevMan statistical software. Bupivacaine and morphine group had similar acute postoperative pain scores (WMD: 0.07; 95% CI, -0.18 to 0.32; P=0.60); number of patients requiring supplementary analgesia (relative risk: 0.74; 95% CI, 0.42 to 1.31; P=0.30) for the trials in this meta-analysis (n=13); and side effects (relative risk: 0.63; 95% CI, 0.39 to 1.02, P=0.06). Even though, the time to first analgesic request resulted in a significant difference (WMD: 66.59; 95% CI, 11.75 to 122.14, P=0.02), this result was not supported by the sensitivity analysis. On the basis of the currently available literature, this study failed to demonstrate a significant difference between single-dose intra-articular bupivacaine and morphine at the end of the arthroscopic knee surgery in terms of pain relief, need for supplementary analgesics, times interval before the first request for additional analgesic, and short-term side effects. Level II-meta-analysis of Level I and II studies.

META-ANALYSIS OF ACUTE EXERCISE EFFECTS ON STATE ANXIETY: AN UPDATE OF RANDOMIZED CONTROLLED TRIALS OVER THE PAST 25 YEARS.

PubMed

Ensari, Ipek; Greenlee, Tina A; Motl, Robert W; Petruzzello, Steven J

2015-08-01

One prominent and well-cited meta-analysis published nearly 25 years ago reported that an acute or single bout of exercise reduced state anxiety by approximately ¼ standard deviation. We conducted a meta-analysis of randomized controlled trials (RCTs) published after that meta-analysis for updating our understanding of the acute effects of exercise on state anxiety. We searched PubMed, EBSCOHost, Medline, PsycINFO, ERIC, and ScienceDirect for RCTs of acute exercise and state anxiety as an outcome. There were 36 RCTs that met inclusion criteria and yielded data for effect size (ES) generation (Cohen's d). An overall ES was calculated using a random effects model and expressed as Hedge's g. The weighted mean ES was small (Hedge's g = 0.16, standard error (SE) = 0.06), but statistically significant (P < 0.05), and indicated that a single bout of exercise resulted in an improvement in state anxiety compared with control. The overall ES was heterogeneous and post hoc, exploratory analyses using both random- and fixed-effects models identified several variables as moderators including sample age, sex and health status, baseline activity levels, exercise intensity, modality and control condition, randomization, overall study quality, and the anxiety measure (P < 0.05). The cumulative evidence from high quality studies indicates that acute bouts of exercise can yield a small reduction in state anxiety. The research is still plagued by floor effects associated with recruiting persons with normal or lower levels of state anxiety, and this should be overcome in subsequent trials. © 2015 Wiley Periodicals, Inc.

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

PubMed Central

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

2011-01-01

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

Testing of the Support Vector Machine for Binary-Class Classification

NASA Technical Reports Server (NTRS)

Scholten, Matthew

2011-01-01

The Support Vector Machine is a powerful algorithm, useful in classifying data in to species. The Support Vector Machines implemented in this research were used as classifiers for the final stage in a Multistage Autonomous Target Recognition system. A single kernel SVM known as SVMlight, and a modified version known as a Support Vector Machine with K-Means Clustering were used. These SVM algorithms were tested as classifiers under varying conditions. Image noise levels varied, and the orientation of the targets changed. The classifiers were then optimized to demonstrate their maximum potential as classifiers. Results demonstrate the reliability of SMV as a method for classification. From trial to trial, SVM produces consistent results

Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis.

PubMed

Raggi, D; Miceli, R; Sonpavde, G; Giannatempo, P; Mariani, L; Galsky, M D; Bellmunt, J; Necchi, A

2016-01-01

The efficacy and safety of a combination of chemotherapeutic agent compared with single-agent chemotherapy in the second-line setting of advanced urothelial carcinoma (UC) are unclear. We aimed to study the survival impact of single-agent compared with doublet chemotherapy as second-line chemotherapy of advanced UC. Literature was searched for studies including single-agent or doublet chemotherapy in the second-line setting after platinum-based chemotherapy. Random-effects models were used to pool trial-level data according to treatment arm, including median progression-free survival (PFS), overall survival (OS), objective response rate (ORR) probability, and grade 3-4 toxicity. Univariable and multivariable analyses, including sensitivity analyses, were carried out, adjusting for the percent of patients with ECOG performance status ≥1 and hepatic metastases. Forty-six arms of trials including 1910 patients were selected: 22 arms with single agent (n = 1202) and 24 arms with doublets (n = 708). The pooled ORR with single agents was 14.2% [95% confidence interval (CI) 11.1-17.9] versus 31.9% [95% CI 27.3-36.9] with doublet chemotherapy. Pooled median PFS was 2.69 and 4.05 months, respectively. The pooled median OS was 6.98 and 8.50 months, respectively. Multivariably, the odds ratio for ORR and the pooled median difference of PFS were statistically significant (P < 0.001 and P = 0.002) whereas the median difference in OS was not (P = 0.284). When including single-agent vinflunine or taxanes only, differences were significant only for ORR (P < 0.001) favoring doublet chemotherapy. No statistically significant differences in grade 3-4 toxicity were seen between the two groups. Despite significant improvements in ORR and PFS, doublet regimens did not extend OS compared with single agents for the second-line chemotherapy of UC. Prospective trials are necessary to elucidate the role of combination chemotherapy, with or without targeted agents, in the salvage setting. Currently, improvements in this field should be pursued considering single-agent chemotherapy as the foundation for new more active combinations. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cortical activity is more stable when sensory stimuli are consciously perceived

PubMed Central

Schurger, Aaron; Sarigiannidis, Ioannis; Naccache, Lionel; Sitt, Jacobo D.; Dehaene, Stanislas

2015-01-01

According to recent evidence, stimulus-tuned neurons in the cerebral cortex exhibit reduced variability in firing rate across trials, after the onset of a stimulus. However, in order for a reduction in variability to be directly relevant to perception and behavior, it must be realized within trial—the pattern of activity must be relatively stable. Stability is characteristic of decision states in recurrent attractor networks, and its possible relevance to conscious perception has been suggested by theorists. However, it is difficult to measure on the within-trial time scales and broadly distributed spatial scales relevant to perception. We recorded simultaneous magneto- and electroencephalography (MEG and EEG) data while subjects observed threshold-level visual stimuli. Pattern-similarity analyses applied to the data from MEG gradiometers uncovered a pronounced decrease in variability across trials after stimulus onset, consistent with previous single-unit data. This was followed by a significant divergence in variability depending upon subjective report (seen/unseen), with seen trials exhibiting less variability. Applying the same analysis across time, within trial, we found that the latter effect coincided in time with a difference in the stability of the pattern of activity. Stability alone could be used to classify data from individual trials as “seen” or “unseen.” The same metric applied to EEG data from patients with disorders of consciousness exposed to auditory stimuli diverged parametrically according to clinically diagnosed level of consciousness. Differences in signal strength could not account for these results. Conscious perception may involve the transient stabilization of distributed cortical networks, corresponding to a global brain-scale decision. PMID:25847997

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study

PubMed Central

Koek, Mayke BG; Buskens, Erik; Steegmans, Paul HA; van Weelden, Huib; Bruijnzeel-Koomen, Carla AFM; Sigurdsson, Vigfús

2006-01-01

Background Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). Methods We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. Discussion In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB phototherapy. Trial registration Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT00150930 PMID:16882343

Primaquine or other 8-aminoquinolines for reducing Plasmodium falciparum transmission.

PubMed

Graves, Patricia M; Choi, Leslie; Gelband, Hellen; Garner, Paul

2018-02-02

The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance. This replaced the previous recommendation of 0.75 mg/kg, aiming to reduce haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malarious areas. Whether this approach, and at this dose, is effective in reducing transmission is not clear. To assess the effects of single dose or short-course PQ (or an alternative 8AQ) alongside treatment for people with P. falciparum malaria. We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; and the WHO International Clinical Trials Registry Platform (ICRTP) portal using 'malaria*', 'falciparum', 'primaquine', '8-aminoquinoline', and eight 8AQ drug names as search terms. We checked reference lists of included trials, and contacted researchers and organizations. Date of last search: 21 July 2017. Randomized controlled trials (RCTs) or quasi-RCTs in children or adults, adding PQ (or alternative 8AQ) as a single dose or short course alongside treatment for P. falciparum malaria. Two authors screened abstracts, applied inclusion criteria, and extracted data. We sought evidence on transmission (community incidence), infectiousness (people infectious and mosquitoes infected), and potential infectiousness (gametocyte measures assessed by microscopy or polymerase chain reaction [PCR]). We grouped trials into artemisinin and non-artemisinin treatments, and stratified by PQ dose (low, 0.2 to 0.25 mg/kg; moderate, 0.4 to 0.5 mg/kg; high, 0.75 mg/kg). We used GRADE, and absolute effects of infectiousness using trial control groups. We included 24 RCTs and one quasi-RCT, comprising 43 arms. Fourteen trials evaluated artemisinin treatments (23 arms), nine trials evaluated non-artemisinin treatments (13 arms), and two trials included both artemisinin and non-artemisinin arms (three and two arms, respectively). Two trial arms used bulaquine. Seven PQ arms used low dose (six with artemisinin), 11 arms used moderate dose (seven with artemisinin), and the remaining arms used high dose. Fifteen trials tested for G6PD status: 11 excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and three included all, irrespective of status. The remaining 10 trials either did not test or did not report on testing.No cluster trials evaluating community effects on malaria transmission met the inclusion criteria.With artemisinin treatmentLow dose PQInfectiousness (participants infectious to mosquitoes) was reduced (day 3 or 4: RR 0.12, 95% CI 0.02 to 0.88, 3 trials, 105 participants; day 8: RR 0.34, 95% CI 0.07 to 1.58, 4 trials, 243 participants; low certainty evidence). This translates to a reduction in percentage of people infectious on day 3 or 4 from 14% to 2%, and, for day 8, from 4% to 1%; the waning infectiousness in the control group by day 8 making the absolute effect smaller by day 8. For gametocytes detected by PCR, there was little or no effect of PQ at day 3 or 4 (RR 1.02, 95% CI 0.87 to 1.21; 3 trials, 414 participants; moderate certainty evidence); with reduction at day 8 (RR 0.52, 95% CI 0.41 to 0.65; 4 trials, 532 participants; high certainty evidence). Severe haemolysis was infrequent, with or without PQ, in these groups with few G6PD-deficient individuals (RR 0.98, 95% CI 0.69 to 1.39; 4 trials, 752 participants, moderate certainty evidence).Moderate dose PQInfectiousness was reduced (day 3 or 4: RR 0.13, 95% CI 0.02 to 0.94; 3 trials, 109 participants; day 8 RR 0.33, 95% CI 0.07 to 1.57; 4 trials, 246 participants; low certainty evidence). Illustrative risk estimates for moderate dose were the same as low dose. The pattern and level of certainty of evidence with gametocytes detected by PCR was the same as low dose, and severe haemolysis was infrequent in both groups.High dose PQInfectiousness was reduced (day 4: RR 0.2, 95% CI 0.02 to 1.68, 1 trial, 101 participants; day 8: RR 0.18, 95% CI 0.02 to 1.41, 2 trials, 181 participants, low certainty evidence). The effects on gametocyte prevalence showed a similar pattern to moderate and low dose PQ. Trials did not systematically report evidence of haemolysis.With non-artemisinin treatmentTrials with non-artemisinin treatment have been conducted only for moderate and high dose PQ. With high dose, infectiousness appeared markedly reduced on day 5 (RR 0.09, 95% CI 0.01 to 0.62; 30 participants, very low certainty evidence), with similar reductions at day 8. For both moderate dose (two trials with 221 people) and high dose (two trials with 30 people), reduction in gametocytes (detected by microscopy) showed similar patterns as for artemisinin treatments, with little or no effect at day 4 or 5, and larger effects by day 8. No trials with non-artemisinin partner drugs systematically sought evidence of severe haemolysis.Two trials comparing bulaquine with PQ suggest bulaquine may have larger effects on gametocytes by microscopy on day 8 (RR 0.41, 95% CI 0.26 to 0.66; 2 trials, 112 participants). A single low dose of PQ (0.25 mg/kg) added to artemisinin-based combination therapy for malaria reduces infectiousness of people to mosquitoes at day 3-4 and day 8, and appears as effective as higher doses. The absolute effect is greater at day 3 or 4, and smaller at day 8, in part because of the lower infectiousness in the control group. There was no evidence of increased haemolysis at 0.25 mg/kg, but few G6PD-deficient individuals were included in the trials. The effect on infectiousness precedes the effect of PQ on gametocyte prevalence. We do not know whether single dose PQ could reduce malaria transmission at community level.

Methodological improvements in quantifying cognitive change in clinical trials: an example with single-dose administration of donepezil.

PubMed

Pietrzak, R H; Maruff, P; Snyder, P J

2009-03-01

Change in cognitive function in response to a pharmacologic challenge can be observed with greater sensitivity by employing cognitive tests with optimal psychometric properties and a statistical approach that more accurately accounts for individual variability in performance. To demonstrate this approach we examined the cognitive effects of a single acute dose administration of an acetylcholinesterase inhibitor, donepezil, in healthy older adults and in older adults with mild Alzheimer's disease (AD). Placebo-controlled crossover study with three separate testing days: baseline, placebo, and donepezil, with assessments at baseline, and 1-, 2-, 3-, 6-, and 8-hrs post-dosing on each day. Early phase I clinical trial. 15 healthy older adults; 14 older adults with mild Alzheimer's disease. Single acute dose of 5mg donepezil. Performance on the Groton Maze Learning Test (GMLT), a computerized neuropsychological measure of spatial working memory and error monitoring. A single acute dose of donepezil improved GMLT performance in healthy older adults (effect size: 0.83 at 6 hrs post-dosing) and older adults with mild AD (effect size: 0.58 at 3 hrs post-dosing). The GMLT detected cognitive improvement following a single, acute dose administration of donepezil in healthy older adults and older adults with mild AD. The choice of cognitive tests designed for repeated administration, as well as an analytic approach that emphasizes individual-level change in cognitive function, provides a sensitive approach to detecting central nervous system drug penetration and activity of cognitive-enhancing agents.

Inorganic nitrate as a treatment for acute heart failure: a protocol for a single center, randomized, double-blind, placebo-controlled pilot and feasibility study.

PubMed

Falls, Roman; Seman, Michael; Braat, Sabine; Sortino, Joshua; Allen, Jason D; Neil, Christopher J

2017-08-08

Acute heart failure (AHF) is a frequent reason for hospitalization worldwide and effective treatment options are limited. It is known that AHF is a condition characterized by impaired vasorelaxation, together with reduced nitric oxide (NO) bioavailability, an endogenous vasodilatory compound. Supplementation of inorganic sodium nitrate (NaNO 3 ) is an indirect dietary source of NO, through bioconversion. It is proposed that oral sodium nitrate will favorably affect levels of circulating NO precursors (nitrate and nitrite) in AHF patients, resulting in reduced systemic vascular resistance, without significant hypotension. We propose a single center, randomized, double-blind, placebo-controlled pilot trial, evaluating the feasibility of sodium nitrate as a treatment for AHF. The primary hypothesis that sodium nitrate treatment will result in increased systemic levels of nitric oxide pre-cursors (nitrate and nitrite) in plasma, in parallel with improved vasorelaxation, as assessed by non-invasively derived systemic vascular resistance index. Additional surrogate measures relevant to the known pathophysiology of AHF will be obtained in order to assess clinical effect on dyspnea and renal function. The results of this study will provide evidence of the feasibility of this novel approach and will be of interest to the heart failure community. This trial may inform a larger study.

Adult Age Differences and the Role of Cognitive Resources in Perceptual–Motor Skill Acquisition: Application of a Multilevel Negative Exponential Model

PubMed Central

Kennedy, Kristen M.; Rodrigue, Karen M.; Lindenberger, Ulman; Raz, Naftali

2010-01-01

The effects of advanced age and cognitive resources on the course of skill acquisition are unclear, and discrepancies among studies may reflect limitations of data analytic approaches. We applied a multilevel negative exponential model to skill acquisition data from 80 trials (four 20-trial blocks) of a pursuit rotor task administered to healthy adults (19–80 years old). The analyses conducted at the single-trial level indicated that the negative exponential function described performance well. Learning parameters correlated with measures of task-relevant cognitive resources on all blocks except the last and with age on all blocks after the second. Thus, age differences in motor skill acquisition may evolve in 2 phases: In the first, age differences are collinear with individual differences in task-relevant cognitive resources; in the second, age differences orthogonal to these resources emerge. PMID:20047985

The effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D: a prospective randomised trial.

PubMed

Haines, N; Kempton, L B; Seymour, R B; Bosse, M J; Churchill, C; Hand, K; Hsu, J R; Keil, D; Kellam, J; Rozario, N; Sims, S; Karunakar, M A

2017-11-01

To evaluate the effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D and a long bone fracture. Between July 2011 and August 2013, 113 adults with a long bone fracture were enrolled in a prospective randomised double-blind placebo-controlled trial. Their serum vitamin D levels were measured and a total of 100 patients were found to be vitamin D deficient (< 20 ng/ml) or insufficient (< 30 ng/mL). These were then randomised to receive a single dose of vitamin D 3 orally (100 000 IU) within two weeks of injury (treatment group, n = 50) or a placebo (control group, n = 50). We recorded patient demographics, fracture location and treatment, vitamin D level, time to fracture union and complications, including vitamin D toxicity. Outcomes included union, nonunion or complication requiring an early, unplanned secondary procedure. Patients without an outcome at 15 months and no scheduled follow-up were considered lost to follow-up. The t -test and cross tabulations verified the adequacy of randomisation. An intention-to-treat analysis was carried out. In all, 100 (89%) patients had hypovitaminosis D. Both treatment and control groups had similar demographics and injury characteristics. The initial median vitamin D levels were 16 ng/mL (interquartile range 5 to 28) in both groups (p = 0.885). A total of 14 patients were lost to follow-up (seven from each group), two had fixation failure (one in each group) and one control group patient developed an infection. Overall, the nonunion rate was 4% (two per group). No patient showed signs of clinical toxicity from their supplement. Despite finding a high level of hypovitaminosis D, the rate of union was high and independent of supplementation with vitamin D 3 . Cite this article: Bone Joint J 2017;99-B:1520-5. ©2017 The British Editorial Society of Bone & Joint Surgery.

Randomised field trial to evaluate serological response after foot-and-mouth disease vaccination in Turkey.

PubMed

Knight-Jones, T J D; Bulut, A N; Gubbins, S; Stärk, K D C; Pfeiffer, D U; Sumption, K J; Paton, D J

2015-02-04

Despite years of biannual mass vaccination of cattle, foot-and-mouth disease (FMD) remains uncontrolled in Anatolian Turkey. To evaluate protection after mass vaccination we measured post-vaccination antibodies in a cohort of cattle (serotypes O, A and Asia-1). To obtain results reflecting typical field protection, participants were randomly sampled from across Central and Western Turkey after routine vaccination. Giving two-doses one month apart is recommended when cattle are first vaccinated against FMD. However, due to cost and logistics, this is not routinely performed in Turkey, and elsewhere. Nested within the cohort, we conducted a randomised trial comparing post-vaccination antibodies after a single-dose versus a two-dose primary vaccination course. Four to five months after vaccination, only a third of single-vaccinated cattle had antibody levels above a threshold associated with protection. A third never reached this threshold, even at peak response one month after vaccination. It was not until animals had received three vaccine doses in their lifetime, vaccinating every six months, that most (64% to 86% depending on serotype) maintained antibody levels above this threshold. By this time cattle would be >20 months old with almost half the population below this age. Consequently, many vaccinated animals will be unprotected for much of the year. Compared to a single-dose, a primary vaccination course of two-doses greatly improved the level and duration of immunity. We concluded that the FMD vaccination programme in Anatolian Turkey did not produce the high levels of immunity required. Higher potency vaccines are now used throughout Turkey, with a two-dose primary course in certain areas. Monitoring post-vaccination serology is an important component of evaluation for FMD vaccination programmes. However, consideration must be given to which antigens are present in the test, the vaccine and the field virus. Differences between these antigens affect the relationship between antibody titre and protection. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Working memory load-dependent spatio-temporal activity of single-trial P3 response detected with an adaptive wavelet denoiser.

PubMed

Zhang, Qiushi; Yang, Xueqian; Yao, Li; Zhao, Xiaojie

2017-03-27

Working memory (WM) refers to the holding and manipulation of information during cognitive tasks. Its underlying neural mechanisms have been explored through both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Trial-by-trial coupling of simultaneously collected EEG and fMRI signals has become an important and promising approach to study the spatio-temporal dynamics of such cognitive processes. Previous studies have demonstrated a modulation effect of the WM load on both the BOLD response in certain brain areas and the amplitude of P3. However, much remains to be explored regarding the WM load-dependent relationship between the amplitude of ERP components and cortical activities, and the low signal-to-noise ratio (SNR) of the EEG signal still poses a challenge to performing single-trial analyses. In this paper, we investigated the spatio-temporal activities of P3 during an n-back verbal WM task by introducing an adaptive wavelet denoiser into the extraction of single-trial P3 features and using general linear model (GLM) to integrate simultaneously collected EEG and fMRI data. Our results replicated the modulation effect of the WM load on the P3 amplitude. Additionally, the activation of single-trial P3 amplitudes was detected in multiple brain regions, including the insula, the cuneus, the lingual gyrus (LG), and the middle occipital gyrus (MOG). Moreover, we found significant correlations between P3 features and behavioral performance. These findings suggest that the single-trial integration of simultaneous EEG and fMRI signals may provide new insights into classical cognitive functions. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Distinct Molecular Phenotypes of Direct vs Indirect ARDS in Single-Center and Multicenter Studies

PubMed Central

Janz, David R.; Bernard, Gordon R.; May, Addison K.; Kangelaris, Kirsten N.; Matthay, Michael A.; Ware, Lorraine B.

2015-01-01

BACKGROUND: ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. METHODS: We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. RESULTS: In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. CONCLUSIONS: Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively. PMID:26033126

Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicenter studies.

PubMed

Calfee, Carolyn S; Janz, David R; Bernard, Gordon R; May, Addison K; Kangelaris, Kirsten N; Matthay, Michael A; Ware, Lorraine B

2015-06-01

ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans. We measured plasma biomarkers of lung epithelial and endothelial injury and inflammation in a single-center study of 100 patients with ARDS and severe sepsis and in a secondary analysis of 853 patients with ARDS drawn from a multicenter randomized controlled trial. Biomarker levels in patients with direct vs indirect ARDS were compared in both cohorts. In both studies, patients with direct ARDS had significantly higher levels of a biomarker of lung epithelial injury (surfactant protein D) and significantly lower levels of a biomarker of endothelial injury (angiopoietin-2) than those with indirect ARDS. These associations were robust to adjustment for severity of illness and ARDS severity. In the multicenter study, patients with direct ARDS also had lower levels of von Willebrand factor antigen and IL-6 and IL-8, markers of endothelial injury and inflammation, respectively. The prognostic value of the biomarkers was similar in direct and indirect ARDS. Direct lung injury in humans is characterized by a molecular phenotype consistent with more severe lung epithelial injury and less severe endothelial injury. The opposite pattern was identified in indirect lung injury. Clinical trials of novel therapies targeted specifically at the lung epithelium or endothelium may benefit from preferentially enrolling patients with direct and indirect ARDS, respectively.

Effect of Psyllium Fiber Supplementation on C-Reactive Protein: The Trial to Reduce Inflammatory Markers (TRIM)

PubMed Central

King, Dana E.; Mainous, Arch G.; Egan, Brent M.; Woolson, Robert F.; Geesey, Mark E.

2008-01-01

PURPOSE Recent evidence supports a significant association between the intake of dietary fiber and levels of inflammatory markers. The objective of this study was to determine whether daily fiber supplementation would reduce levels of inflammatory markers. METHODS This study was a prospective randomized controlled trial at a single university medical center. Participants were overweight or obese adults with no history of heart disease. The intervention was psyllium supplementation at either 7 or 14 g/d for 3 months compared with no supplements in a control group. The main outcome measure was change in level of high-sensitivity C-reactive protein (hsCRP) concentration; secondary outcomes included changes in interleukin-6 (IL-6) levels, fibrinogen levels, and white blood cell (WBC) count. Protocol completers attended at least 2 visits and took more than 75% of the prescribed fiber dose. RESULTS In this intent-to-treat analysis (n = 158), there were no significant differences between either of the 2 treatment groups and the control group in the amount of change in CRP, fibrinogen, or IL-6 levels or in WBC count (P>.05). In the analysis of protocol completers (n = 132), there also were no significant differences between the groups except for a small decrease in fibrinogen level in the high-fiber group (−6 mg/dL [−0.18 μmol/L] compared with 13 mg/dL [0.38 μmol/L] in the control group, P<.05). CONCLUSION Psyllium fiber supplementation did not significantly reduce CRP levels in overweight or obese individuals in this trial, and changes in other markers were not consistent. Further research is needed to determine whether other fibers or nutrients can reduce inflammatory markers. PMID:18332401

Comparison of data transformation procedures to enhance topographical accuracy in time-series analysis of the human EEG.

PubMed

Hauk, O; Keil, A; Elbert, T; Müller, M M

2002-01-30

We describe a methodology to apply current source density (CSD) and minimum norm (MN) estimation as pre-processing tools for time-series analysis of single trial EEG data. The performance of these methods is compared for the case of wavelet time-frequency analysis of simulated gamma-band activity. A reasonable comparison of CSD and MN on the single trial level requires regularization such that the corresponding transformed data sets have similar signal-to-noise ratios (SNRs). For region-of-interest approaches, it should be possible to optimize the SNR for single estimates rather than for the whole distributed solution. An effective implementation of the MN method is described. Simulated data sets were created by modulating the strengths of a radial and a tangential test dipole with wavelets in the frequency range of the gamma band, superimposed with simulated spatially uncorrelated noise. The MN and CSD transformed data sets as well as the average reference (AR) representation were subjected to wavelet frequency-domain analysis, and power spectra were mapped for relevant frequency bands. For both CSD and MN, the influence of noise can be sufficiently suppressed by regularization to yield meaningful information, but only MN represents both radial and tangential dipole sources appropriately as single peaks. Therefore, when relating wavelet power spectrum topographies to their neuronal generators, MN should be preferred.

Prospective randomized clinical trial: single and weekly viscosupplementation

PubMed Central

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

2013-01-01

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

Acute effects of a single exercise class on appetite, energy intake and mood. Is there a time of day effect?

PubMed

Maraki, M; Tsofliou, F; Pitsiladis, Y P; Malkova, D; Mutrie, N; Higgins, S

2005-12-01

This study aimed to investigate the acute effects of a single exercise class on appetite sensations, energy intake and mood, and to determine if there was a time of day effect. Twelve healthy, young, normal weight females, who were non-regular exercisers, participated in four trials: morning control, morning exercise, evening control and evening exercise. Exercise trials were a one-hour class of aerobic and muscle conditioning exercise of varying intensities, to music. Control trials were a one-hour rest. Ratings of perceived exertion were significantly greater during the warm-up and muscle conditioning parts of the morning exercise trial compared to those of the evening exercise trial. Although both exercise trials, compared to control trials, produced an increase in appetite sensations, they did not alter energy intake and produced a decrease in 'relative' energy intake. In relation to mood, both exercise trials increased positive affect and decreased negative affect. These results suggest that a single exercise class, representative of that offered by many sports centres, regardless of whether it is performed in the morning or evening produces a short-term negative energy balance and improves mood in normal weight women. However, when this type of exercise was performed in the morning it was perceived to require more effort.

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

PubMed

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

2016-02-01

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

A Phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study.

PubMed

McCarthy, James S; Rückle, Thomas; Djeriou, Elhadj; Cantalloube, Cathy; Ter-Minassian, Daniel; Baker, Mark; O'Rourke, Peter; Griffin, Paul; Marquart, Louise; Hooft van Huijsduijnen, Rob; Möhrle, Jörg J

2016-09-13

Ferroquine (SSR97193) is a candidate anti-malarial currently undergoing clinical trials for malaria. To better understand its pharmacokinetic (PK) and pharmacodynamic (PD) parameters the compound was tested in the experimentally induced blood stage malaria infection model in volunteers. Male and non-pregnant female aged 18-50 years were screened for this phase II, controlled, single-centre clinical trial. Subjects were inoculated with ~1800 viable Plasmodium falciparum 3D7A-infected human erythrocytes, and treated with a single-dose of 800 mg ferroquine. Blood samples were taken at defined time-points to measure PK and PD parameters. The blood concentration of ferroquine and its active metabolite, SSR97213, were measured on dry blood spot samples by ultra-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Parasitaemia and emergence of gametocytes were monitored by quantitative PCR. Safety was determined by recording adverse events and monitoring clinical laboratory assessments during the course of the study. Eight subjects were enrolled into the study, inoculated with infected erythrocytes and treated with 800 mg ferroquine. Ferroquine was rapidly absorbed with maximal exposure after 4-8 and 4-12 h exposure for SSR97213. Non-compartmental PK analysis resulted in estimates for half-lives of 10.9 and 23.8 days for ferroquine and SSR97213, respectively. Parasite clearance as reported by parasite reduction ratio was 162.9 (95 % CI 141-188) corresponding to a parasite clearance half-life of 6.5 h (95 % CI: 6.4-6.7 h). PK/PD modelling resulted in a predicted minimal parasiticidal concentration of 20 ng/mL, and the single dosing tested in this study was predicted to maintain an exposure above this threshold for 454 h (37.8 days). Although ferroquine was overall well tolerated, transient elevated transaminase levels were observed in three subjects. Paracetamol was the only concomitant treatment among the two out of these three subjects that may have played a role in the elevated transaminases levels. No clinically significant ECG abnormalities were observed. The parameters and PK/PD model derived from this study pave the way to the further rational development of ferroquine as an anti-malarial partner drug. The safety of ferroquine has to be further explored in controlled human trials. Trial registration anzctr.org.au (registration number: ACTRN12613001040752), registered 18/09/2013.

Stemming the Tide of Antibiotic Resistance (STAR): A protocol for a trial of a complex intervention addressing the 'why' and 'how' of appropriate antibiotic prescribing in general practice

PubMed Central

Simpson, Sharon A; Butler, Christopher C; Hood, Kerry; Cohen, David; Dunstan, Frank; Evans, Meirion R; Rollnick, Stephen; Moore, Laurence; Hare, Monika; Bekkers, Marie-Jet; Evans, John

2009-01-01

Background After some years of a downward trend, antibiotic prescribing rates in the community have tended to level out in many countries. There is also wide variation in antibiotic prescribing between general practices, and between countries. There are still considerable further gains that could be made in reducing inappropriate antibiotic prescribing, but complex interventions are required. Studies to date have generally evaluated the effect of interventions on antibiotic prescribing in a single consultation and pragmatic evaluations that assess maintenance of new skills are rare. This paper describes the protocol for a pragmatic, randomized evaluation of a complex intervention aimed at reducing antibiotic prescribing by primary care clinicians. Methods and design We developed a Social Learning Theory based, blended learning program (on-line learning, a practice based seminar, and context bound learning) called the STAR Educational Program. The 'why of change' is addressed by providing clinicians in general practice with information on antibiotic resistance in urine samples submitted by their practice and their antibiotic prescribing data, and facilitating a practice-based seminar on the implications of this data. The 'how of change' is addressed through context-bound communication skills training and information on antibiotic indication and choice. This intervention will be evaluated in a trial involving 60 general practices, with general practice as the unit of randomization (clinicians from each practice to either receive the STAR Educational Program or not) and analysis. The primary outcome will be the number of antibiotic items dispensed over one year. An economic and process evaluation will also be conducted. Discussion This trial will be the first to evaluate the effectiveness of this type of theory-based, blended learning intervention aimed at reducing antibiotic prescribing by primary care clinicians. Novel aspects include feedback of practice level data on antimicrobial resistance and prescribing, use of principles from motivational interviewing, training in enhanced communication skills that incorporates context-bound experience and reflection, and using antibiotic dispensing over one year (as opposed to antibiotic prescribing in a single consultation) as the main outcome. Trial registration Current Controlled Trials ISRCTN63355948. PMID:19309493

Exercise training and weight loss, not always a happy marriage: single blind exercise trials in females with diverse BMI.

PubMed

Jackson, Matthew; Fatahi, Fardin; Alabduljader, Kholoud; Jelleyman, Charlotte; Moore, Jonathan P; Kubis, Hans-Peter

2018-04-01

Individuals show high variability in body weight responses to exercise training. Expectations and motivation towards effects of exercise on body weight might influence eating behaviour and could conceal regulatory mechanisms. We conducted 2 single-blind exercise trials (4 weeks (study 1) and 8 weeks (study 2)) with concealed objectives and exclusion of individuals with weight loss intention. Circuit exercise training programs (3 times a week (45-90 min), intensity 50%-90% peak oxygen uptake for 4 and 8 weeks) were conducted. Thirty-four females finished the 4-week intervention and 36 females the 8-week intervention. Overweight/obese (OV/OB) and lean female participants' weight/body composition responses were assessed and fasting and postprandial appetite hormone levels (PYY, insulin, amylin, leptin, ghrelin) were measured before and after the intervention for understanding potential contribution to individuals' body weight response to exercise training (study 2). Exercise training in both studies did not lead to a significant reduction of weight/body mass index (BMI) in the participants' groups; however, lean participants gained muscle mass. Appetite hormones levels were significantly (p < 0.05) altered in the OV/OB group, affecting fasting (-24%) and postprandial amylin (-14%) levels. Investigation of individuals' BMI responses using multiple regression analysis revealed that levels of fasting leptin, postprandial amylin increase, and BMI were significant predictors of BMI change, explaining about 43% of the variance. In conclusion, tested exercise training did not lead to weight loss in female participants, while a considerable proportion of variance in body weight response to training could be explained by individuals' appetite hormone levels and BMI.

Single-visit or multiple-visit root canal treatment: systematic review, meta-analysis and trial sequential analysis.

PubMed

Schwendicke, Falk; Göstemeyer, Gerd

2017-02-01

Single-visit root canal treatment has some advantages over conventional multivisit treatment, but might increase the risk of complications. We systematically evaluated the risk of complications after single-visit or multiple-visit root canal treatment using meta-analysis and trial-sequential analysis. Controlled trials comparing single-visit versus multiple-visit root canal treatment of permanent teeth were included. Trials needed to assess the risk of long-term complications (pain, infection, new/persisting/increasing periapical lesions ≥1 year after treatment), short-term pain or flare-up (acute exacerbation of initiation or continuation of root canal treatment). Electronic databases (PubMed, EMBASE, Cochrane Central) were screened, random-effects meta-analyses performed and trial-sequential analysis used to control for risk of random errors. Evidence was graded according to GRADE. 29 trials (4341 patients) were included, all but 6 showing high risk of bias. Based on 10 trials (1257 teeth), risk of complications was not significantly different in single-visit versus multiple-visit treatment (risk ratio (RR) 1.00 (95% CI 0.75 to 1.35); weak evidence). Based on 20 studies (3008 teeth), risk of pain did not significantly differ between treatments (RR 0.99 (95% CI 0.76 to 1.30); moderate evidence). Risk of flare-up was recorded by 8 studies (1110 teeth) and was significantly higher after single-visit versus multiple-visit treatment (RR 2.13 (95% CI 1.16 to 3.89); very weak evidence). Trial-sequential analysis revealed that firm evidence for benefit, harm or futility was not reached for any of the outcomes. There is insufficient evidence to rule out whether important differences between both strategies exist. Dentists can provide root canal treatment in 1 or multiple visits. Given the possibly increased risk of flare-ups, multiple-visit treatment might be preferred for certain teeth (eg, those with periapical lesions). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Grand average ERP-image plotting and statistics: A method for comparing variability in event-related single-trial EEG activities across subjects and conditions

PubMed Central

Delorme, Arnaud; Miyakoshi, Makoto; Jung, Tzyy-Ping; Makeig, Scott

2014-01-01

With the advent of modern computing methods, modeling trial-to-trial variability in biophysical recordings including electroencephalography (EEG) has become of increasingly interest. Yet no widely used method exists for comparing variability in ordered collections of single-trial data epochs across conditions and subjects. We have developed a method based on an ERP-image visualization tool in which potential, spectral power, or some other measure at each time point in a set of event-related single-trial data epochs are represented as color coded horizontal lines that are then stacked to form a 2-D colored image. Moving-window smoothing across trial epochs can make otherwise hidden event-related features in the data more perceptible. Stacking trials in different orders, for example ordered by subject reaction time, by context-related information such as inter-stimulus interval, or some other characteristic of the data (e.g., latency-window mean power or phase of some EEG source) can reveal aspects of the multifold complexities of trial-to-trial EEG data variability. This study demonstrates new methods for computing and visualizing grand ERP-image plots across subjects and for performing robust statistical testing on the resulting images. These methods have been implemented and made freely available in the EEGLAB signal-processing environment that we maintain and distribute. PMID:25447029

Beneficial Effects of Pentoxifylline Plus Losartan Dual Therapy in Type 2 Diabetes with Nephropathy.

PubMed

Rabizadeh, Soghra; Dehghani Firouzabadi, Fatemeh; Noshad, Sina; Esteghamati, Sadaf; Afarideh, Mohsen; Ghajar, Alireza; Ganji, Morsaleh; Saadat, Mohammad; Heidari, Behnam; Najafi, Mohammad Taghi; Nakhjavani, Manouchehr; Esteghamati, Alireza

2018-05-01

This study was designed to comparatively assess the effects of add-on pentoxifylline to losartan versus increasing the dose of losartan on serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum highly sensitive C-reactive protein (hsCRP) and the urinary albumin excretion (UAE) rate in patients with type 2 diabetes and nephropathy. In an open-label, single-center, parallel-group, randomized clinical trial (NCT03006952), 30 patients received b.i.d. dose of pentoxifylline 400mg plus daily dose of losartan 50mg (pentoxifylline arm) and 29 patients received b.i.d. dose of losartan 50mg (losartan arm) during a 12-week follow-up period. Serum NT-proBNP, serum hsCRP and UAE levels all significantly decreased from baseline in both trial arms. The pentoxifylline and losartan trial arms were equally effective in reducing serum NT-proBNP levels during the course of trial (multivariable adjusted model P value = 0.864, effect size = 0.2%). There was a greater decrease in UAE and serum hsCRP levels in the pentoxifylline arm (P = 0.034, effect size = 7.8%; P = 0.009, effect size = 11.7%, respectively). Conversely, patients in the losartan arm achieved better systolic and diastolic blood pressure control (P < 0.001, effect size = 25.4%; P = 0.010, effect size = 11.3%, respectively). Circulating NT-proBNP levels equally and significantly reduced from baseline in the pentoxifylline and losartan treatment arms, in parallel with comparatively superior decreases of UAE and serum hsCRP in the pentoxifylline arm, and larger decreases of systolic and diastolic blood pressures in the losartan arm. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Effects of acute alcohol intoxication on automated processing: evidence from the double-step paradigm.

PubMed

Vorstius, Christian; Radach, Ralph; Lang, Alan R

2012-02-01

Reflexive and voluntary levels of processing have been studied extensively with respect to possible impairments due to alcohol intoxication. This study examined alcohol effects at the 'automated' level of processing essential to many complex visual processing tasks (e.g., reading, visual search) that involve ongoing modifications or reprogramming of well-practiced routines. Data from 30 participants (16 male) were collected in two counterbalanced sessions (alcohol vs. no-alcohol control; mean breath alcohol concentration = 68 mg/dL vs. 0 mg/dL). Eye movements were recorded during a double-step task where 75% of trials involved two target stimuli in rapid succession (inter-stimulus interval [ISI]=40, 70, or 100 ms) so that they could elicit two distinct saccades or eye movements (double steps). On 25% of trials a single target appeared. Results indicated that saccade latencies were longer under alcohol. In addition, the proportion of single-step responses and the mean saccade amplitude (length) of primary saccades decreased significantly with increasing ISI. The key novel finding, however, was that the reprogramming time needed to cancel the first saccade and adjust saccade amplitude was extended significantly by alcohol. The additional time made available by prolonged latencies due to alcohol was not utilized by the saccade programming system to decrease the number of two-step responses. These results represent the first demonstration of specific alcohol-induced programming deficits at the automated level of oculomotor processing.

Video-game based exercises for older people with chronic low back pain: a protocol for a feasibility randomised controlled trial (the GAMEBACK trial).

PubMed

Zadro, Joshua Robert; Shirley, Debra; Simic, Milena; Mousavi, Seyed Javad; Ceprnja, Dragana; Maka, Katherine; Ferreira, Paulo

2017-06-01

To investigate the feasibility of implementing a video-game exercise programme for older people with chronic low back pain (LBP). Single-centred single-blinded randomised controlled trial (RCT). Physiotherapy outpatient department in a public hospital in Western Sydney, Australia. We will recruit 60 participants over 55 years old with chronic LBP from the waiting list. Participants will be randomised to receive video-game exercise (n=30) or to remain on the waiting list (n=30) for 8 weeks, with follow up at 3 and 6 months. Participants engaging in video-game exercises will be unsupervised and will complete video-game exercise for 60minutes, 3 times per week. Participants allocated to remain on the waiting list will be encouraged to maintain their usual levels of physical activity. The primary outcomes for this feasibility study will be study processes (recruitment and response rates, adherence to and experience with the intervention, and incidence of adverse events) relevant to the future design of a large RCT. Estimates of treatment efficacy (point estimates and 95% confidence intervals) on pain self-efficacy, care seeking, physical activity, fear of movement/re-injury, pain, physical function, disability, falls-efficacy, strength, and walking speed, will be our secondary outcome measures. Recruitment for this trial began in November 2015. This study describes the rationale and processes of a feasibility study investigating a video-game exercise programme for older people with chronic LBP. Results from the feasibility study will inform on the design and sample required for a large multicentre RCT. Australian New Zealand Clinical Trials Registry: ACTRN12615000703505. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Decoding the individual finger movements from single-trial functional magnetic resonance imaging recordings of human brain activity.

PubMed

Shen, Guohua; Zhang, Jing; Wang, Mengxing; Lei, Du; Yang, Guang; Zhang, Shanmin; Du, Xiaoxia

2014-06-01

Multivariate pattern classification analysis (MVPA) has been applied to functional magnetic resonance imaging (fMRI) data to decode brain states from spatially distributed activation patterns. Decoding upper limb movements from non-invasively recorded human brain activation is crucial for implementing a brain-machine interface that directly harnesses an individual's thoughts to control external devices or computers. The aim of this study was to decode the individual finger movements from fMRI single-trial data. Thirteen healthy human subjects participated in a visually cued delayed finger movement task, and only one slight button press was performed in each trial. Using MVPA, the decoding accuracy (DA) was computed separately for the different motor-related regions of interest. For the construction of feature vectors, the feature vectors from two successive volumes in the image series for a trial were concatenated. With these spatial-temporal feature vectors, we obtained a 63.1% average DA (84.7% for the best subject) for the contralateral primary somatosensory cortex and a 46.0% average DA (71.0% for the best subject) for the contralateral primary motor cortex; both of these values were significantly above the chance level (20%). In addition, we implemented searchlight MVPA to search for informative regions in an unbiased manner across the whole brain. Furthermore, by applying searchlight MVPA to each volume of a trial, we visually demonstrated the information for decoding, both spatially and temporally. The results suggest that the non-invasive fMRI technique may provide informative features for decoding individual finger movements and the potential of developing an fMRI-based brain-machine interface for finger movement. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Single, double or multiple-injection techniques for non-ultrasound guided axillary brachial plexus block in adults undergoing surgery of the lower arm.

PubMed

Chin, Ki Jinn; Alakkad, Husni; Cubillos, Javier E

2013-08-08

Regional anaesthesia comprising axillary block of the brachial plexus is a common anaesthetic technique for distal upper limb surgery. This is an update of a review first published in 2006 and updated in 2011. To compare the relative effects (benefits and harms) of three injection techniques (single, double and multiple) of axillary block of the brachial plexus for distal upper extremity surgery. We considered these effects primarily in terms of anaesthetic effectiveness; the complication rate (neurological and vascular); and pain and discomfort caused by performance of the block. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and reference lists of trials. We contacted trial authors. The date of the last search was March 2013 (updated from March 2011). We included randomized controlled trials that compared double with single-injection techniques, multiple with single-injection techniques, or multiple with double-injection techniques for axillary block in adults undergoing surgery of the distal upper limb. We excluded trials using ultrasound-guided techniques. Independent study selection, risk of bias assessment and data extraction were performed by at least two investigators. We undertook meta-analysis. The 21 included trials involved a total of 2148 participants who received regional anaesthesia for hand, wrist, forearm or elbow surgery. Risk of bias assessment indicated that trial design and conduct were generally adequate; the most common areas of weakness were in blinding and allocation concealment.Eight trials comparing double versus single injections showed a statistically significant decrease in primary anaesthesia failure (risk ratio (RR 0.51), 95% confidence interval (CI) 0.30 to 0.85). Subgroup analysis by method of nerve location showed that the effect size was greater when neurostimulation was used rather than the transarterial technique.Eight trials comparing multiple with single injections showed a statistically significant decrease in primary anaesthesia failure (RR 0.25, 95% CI 0.14 to 0.44) and of incomplete motor block (RR 0.61, 95% CI 0.39 to 0.96) in the multiple injection group.Eleven trials comparing multiple with double injections showed a statistically significant decrease in primary anaesthesia failure (RR 0.28, 95% CI 0.20 to 0.40) and of incomplete motor block (RR 0.55, 95% CI 0.36 to 0.85) in the multiple injection group.Tourniquet pain was significantly reduced with multiple injections compared with double injections (RR 0.53, 95% CI 0.33 to 0.84). Otherwise there were no statistically significant differences between groups in any of the three comparisons on secondary analgesia failure, complications and patient discomfort. The time for block performance was significantly shorter for single and double injections compared with multiple injections. This review provides evidence that multiple-injection techniques using nerve stimulation for axillary plexus block produce more effective anaesthesia than either double or single-injection techniques. However, there was insufficient evidence for a significant difference in other outcomes, including safety.

A new fully human recombinant FSH (follitropin epsilon): two phase I randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials.

PubMed

Abd-Elaziz, Khalid; Duijkers, Ingrid; Stöckl, Lars; Dietrich, Bruno; Klipping, Christine; Eckert, Kelvin; Goletz, Steffen

2017-08-01

What are the differences and similarities of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the novel recombinant human FSH follitropin epsilon expressed in the human cell line GlycoExpress compared with a Chinese hamster ovary (CHO) derived compound and a urinary derived product? Overall follitropin epsilon, with a fully human glycosylation, shows a comparable PK profile at single-dose as well as multiple-dose administration compared to recombinant CHO-derived FSH as well as urinary derived FSH, whereas the PD properties differ from product to product with follitropin epsilon being most active in PD parameters. Recombinant FSH produced in CHO and FSH obtained from the urine of postmenopausal women show comparable PK and PD properties. However, more recently a comparative study of a recombinant FSH produced in the human cell line PerC6 and a CHO-derived FSH preparation revealed differences in PK and PD properties of the molecule. Both studies were randomized, placebo- and comparator-controlled, single-blind phase I studies in healthy pituitary-suppressed female volunteers aged 18 and 40 years. The single-dose, dose escalation study included 19 women (April 2011 to September 2011) with three ascending dose levels per subject or placebo/comparators with a 14-day washout phase between dosings. The multiple-dose study included 57 women (October 2011 to April 2012) in five cohorts with three dose levels versus placebo and two comparators. Randomization to the respective treatment was performed after successful downregulation of the pituitary gland prior to Investigational Medicinal Product dosing. In the single-dose study, 12 subjects received follitropin epsilon (25, 75, 150 and 300 IU) in three of four possible ascending doses and seven subjects received one dose of two comparators (150 IU Bravelle and 150 IU Gonal-f) and placebo in random order in each treatment period. In the multiple-dose study, 30 subjects received follitropin epsilon (75 IU or 150 IU once daily [QD], or 150 IU every other day [QAD], 10 subjects each) and 27 subjects received 150 IU Gonal-f, 150 IU Bravelle, or placebo for 7 days (11/10/6 subjects). Blood samples for measuring PK as well as PD parameters were collected systematically before, during and after dosing. Adverse events (AEs) and other relevant safety parameters were recorded. Data were summarized using descriptive statistics. The single- and multiple-dose PK parameters maximum concentration (Cmax) and area under the concentration-time curve (AUC0-last) increased in a linear fashion with increasing dose levels of follitropin epsilon. Follitropin epsilon showed PK characteristics comparable to the comparators indicating that well established treatment schemes could be applied. There was a dose-response effect of single and multiple doses of follitropin epsilon on follicular growth, which was shown for the biomarker inhibin B as well as for the mean number and size of follicles. Multiple doses of 75 IU follitropin epsilon given daily, as well as 150 IU follitropin epsilon every second day, showed a follicle growth comparable with 150 IU Gonal-f given daily, while in case of daily administration of 150 IU Bravelle only weak follicle stimulation was observed. Multiple doses of 150 IU follitropin epsilon induced a much higher follicle growth compared to the same dose of Gonal-f. All single and multiple follitropin epsilon doses tested were safe and well tolerated, and overall there were no relevant differences between follitropin epsilon and the comparators in terms of safety. The average number of AEs increased with increasing dose levels. No clinically relevant abnormalities were reported for any of the other safety parameters assessed. No follitropin epsilon anti-drug antibodies were observed. The studies were conducted as a single-blind design. Hormone levels or other parameters assessed in serum are generally not considered as being subject to bias. Other assessments directly performed by the investigators, such as transvaginal ultrasound assessments, may have been subject to personal bias. No prospective calculations of statistical power had been made, as is common practice for first in human and early phase I studies in healthy volunteers. These early development studies showed that follitropin epsilon exhibits comparable PK characteristics, as well as inducing stronger PD effects in terms of follicle growth and serum inhibin B, than the comparators. Follitropin epsilon induced a dose-dependent increase in follicular growth. The results warrant further studies with this new fully human recombinant FSH. The studies were sponsored by GLYCOTOPE GmbH, Berlin, Germany. K.A-E. is an employee of QPS-Netherlands, B.V., which received funding for the studies from Glycotope GmbH; I.D. and C.K. are employees of Dinox B.V., which received funding for the studies from Glycotope GmbH; L.S. and S.G. are employees and shareholders of Glycotope GmbH; B.D. and K.E. are employees of Glycotope GmbH. www.clinicaltrials.gov: NCT01354886 (single-dose); NCT01477073 (multiple-dose). The single-dose trial was registered on 11 May 2011 while the multiple-dose trial was registered on 09 November 2011. First subject was enroled in the single-dose trial in 27 April 2011 and in the multiple-dose trial in 02 October 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases

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

Mehta, Minesh P.; Tsao, May N.; Whelan, Timothy J.

2005-09-01

Purpose: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), andmore » the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. Conclusions: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of life outcomes are different between initial radiosurgery alone vs. whole-brain radiotherapy (with or without radiosurgery boost) is unknown, because this has not been adequately tested. There was no statistically significant difference in overall toxicity between those treated with radiosurgery alone vs. whole-brain radiotherapy and radiosurgery boost based on an interim report from one randomized study. There is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented.« less

Single versus recurrent depression history: differentiating risk factors among current US smokers.

PubMed

Strong, David R; Cameron, Amy; Feuer, Shelley; Cohn, Amy; Abrantes, Ana M; Brown, Richard A

2010-06-01

The strong relationship between persistent tobacco use and Major Depressive Disorder (MDD) has motivated clinical trials of specialized treatments targeting smokers with a history of MDD. Meta-analyses suggest positive responses to specialized treatments have been observed consistently among smokers with history of recurrent rather than a single episode of MDD. Approximately 15% of current US smokers have a history of recurrent MDD. Little is known about the risk factors that contribute to persistent smoking and differentiate these at-risk smokers, US. The National Comorbidity Survey - Replication (NCS-R) included a survey of 1560 smokers participants aged 18 and older in the United States. Lifetime history of MDD was categorized according to chronicity: no history (No MDD), single episode (MDD-S) and recurrent depression (MDD-R). The relationship between the chronicity of MDD, smoking characteristics, cessation history, nicotine dependence, comorbidity with psychiatric disorders, and current functional impairments were examined. MDD-R smokers reported fewer lifetime cessation efforts, smoked more cigarettes, had higher levels of nicotine dependence, had higher rates of comorbid psychiatric disorders and greater functional impairment than smokers with No MDD. MDD-S smokers were not consistently distinguished from No MDD smokers on cessation attempts, level of daily smoking, nicotine dependence or functional impairment indices. The study highlights the importance of chronicity when characterizing depression-related risk of persistent smoking behavior. Although, clinical trials suggest MDD-R smokers specifically benefit from specialized behavioral treatments, these services are not widely available and more efforts are needed to engage MDD-R smokers in efficacious treatments. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Reducing multi-sensor data to a single time course that reveals experimental effects

PubMed Central

2013-01-01

Background Multi-sensor technologies such as EEG, MEG, and ECoG result in high-dimensional data sets. Given the high temporal resolution of such techniques, scientific questions very often focus on the time-course of an experimental effect. In many studies, researchers focus on a single sensor or the average over a subset of sensors covering a “region of interest” (ROI). However, single-sensor or ROI analyses ignore the fact that the spatial focus of activity is constantly changing, and fail to make full use of the information distributed over the sensor array. Methods We describe a technique that exploits the optimality and simplicity of matched spatial filters in order to reduce experimental effects in multivariate time series data to a single time course. Each (multi-sensor) time sample of each trial is replaced with its projection onto a spatial filter that is matched to an observed experimental effect, estimated from the remaining trials (Effect-Matched Spatial filtering, or EMS filtering). The resulting set of time courses (one per trial) can be used to reveal the temporal evolution of an experimental effect, which distinguishes this approach from techniques that reveal the temporal evolution of an anatomical source or region of interest. Results We illustrate the technique with data from a dual-task experiment and use it to track the temporal evolution of brain activity during the psychological refractory period. We demonstrate its effectiveness in separating the means of two experimental conditions, and in significantly improving the signal-to-noise ratio at the single-trial level. It is fast to compute and results in readily-interpretable time courses and topographies. The technique can be applied to any data-analysis question that can be posed independently at each sensor, and we provide one example, using linear regression, that highlights the versatility of the technique. Conclusion The approach described here combines established techniques in a way that strikes a balance between power, simplicity, speed of processing, and interpretability. We have used it to provide a direct view of parallel and serial processes in the human brain that previously could only be measured indirectly. An implementation of the technique in MatLab is freely available via the internet. PMID:24125590

Initiating change locally in bullying and aggression through the school environment (INCLUSIVE): study protocol for a cluster randomised controlled trial.

PubMed

Bonell, Chris; Allen, Elizabeth; Christie, Deborah; Elbourne, Diana; Fletcher, Adam; Grieve, Richard; LeGood, Rosa; Mathiot, Anne; Scott, Stephen; Wiggins, Meg; Viner, Russell M

2014-09-30

Systematic reviews suggest that interventions that address school organisation are effective in reducing victimisation and bullying. We successfully piloted a school environment intervention modified from international studies to incorporate 'restorative justice' approaches. This trial aims to establish the effectiveness and cost-effectiveness of the INCLUSIVE intervention in reducing aggression and bullying in English secondary schools. cluster randomised trial. 40 state-supported secondary schools. OUTCOMES assessed among the cohort of students in year 8 (n = approximately 6,000) in intervention year 1. INCLUSIVE is a school-led intervention which combines changes to the school environment with the promotion of social and emotional skills and restorative practices through: the formation of a school action group involving students and staff supported by an external facilitator to review local data on needs, determine priorities, and develop and implement an action plan for revising relevant school policies/rules and other actions to improve relationships at school and reduce aggression; staff training in restorative practices; and a new social and emotional skills curriculum. The intervention will be delivered by schools supported in the first two years by educational facilitators independent of the research team, with a third locally facilitated intervention year.Comparator: normal practice. primary: 2 primary outcomes at student level assessed at baseline and at 36 months:1. Aggressive behaviours in school: Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale (ESYTC)2. Bullying and victimisation: Gatehouse Bullying Scale (GBS)Secondary outcomes assessed at baseline, 24 and 36 months will include measures relating to the economic evaluation, psychosocial outcomes in students and staff and school-level truancy and exclusion rates. 20 schools per arm will provide 90% power to identify an effect size of 0.25 SD with a 5% significance level.Randomisation: eligible consenting schools will be randomised stratified for single sex versus mixed sex schools, school-level deprivation and measures of school attainment. The trial will be run by independent research and intervention teams and supervised by a Trial Steering Committee and a Data Monitoring Committee (DMC). Current Controlled Trials ISRCTN10751359 (Registered 11 March 2014).

Training, executive, attention and motor skills (TEAMS) training versus standard treatment for preschool children with attention deficit hyperactivity disorder: a randomised clinical trial.

PubMed

Vibholm, Helle Annette; Pedersen, Jesper; Faltinsen, Erlend; Marcussen, Michael H; Gluud, Christian; Storebø, Ole Jakob

2018-06-08

This study compared the effectiveness of manualised training, executive, attention, and motor skills (TEAMS) training versus standard treatment in preschool children with attention deficit hyperactivity disorder (ADHD). We conducted a randomised parallel group, single-blinded, superiority trial. The primary outcome was ADHD symptoms and the secondary outcome was functionality. Parents and primary school teachers assessed outcomes at pretreatment, posttreatment, and at one, three, and 6 months follow-up. In total, 67 children (aged 3-6 years) were randomised. In the TEAMS group, 32 out of 33 (97%) participants completed the total 8-week program, compared with only 7 out of 26 (27%) in the control group. The repeated-model analyses showed no significant change between the two interventions for ADHD symptoms and functionality levels over time. The mean difference in ADHD symptoms between TEAMS versus standard treatment at posttreatment was 2.18 points (95% confidence interval - 8.62 to 13.0; trial sequential analysis-adjusted confidence interval - 19.3 to 23.7). Trial registration Clinical Trials identifier: NCT01918436 (Retrospectively registered). Registered on 7 August 2013.

Bone-level implants placed in the anterior maxilla: an open-label, single-arm observational study

PubMed Central

2017-01-01

Purpose This study assessed marginal bone remodeling and soft tissue esthetics after the loading of single bone-level implants in the anterior maxilla. Methods An open, single-arm observational clinical trial with 3 years of follow-up was performed, including 22 implants. The patients presented with a single tooth gap in the anterior maxilla (tooth positions 14–24), with natural or restored adjacent teeth. An implant was placed at least 8 weeks post-extraction and healed submerged for 6 weeks. After the second-stage operation, a fixed provisional prosthesis was provided. The final restoration was placed 6 months after the provisional restoration. The time of the provisional crown connection was considered to be the baseline in this study. Esthetic parameters and the marginal bone level were assessed at 6, 12, 24, and 36 months. Results All implants were well integrated in the bone. A statistically significant increase was found in the mean implant stability quotient between the time of the provisional prosthesis and the time of the final prosthesis. Most implants (95.5%) revealed marginal bone resorption (<0.5 mm), and just 1 implant (4.5%) showed a change of 2.12 mm from baseline to 36 months (mean 0.07±0.48 mm), while the crestal bone level decreased significantly, from 2.34±0.93 mm at baseline to 1.70±1.10 mm at 36 months. The facial gingival margin and papilla were stable and the esthetic scores indicated high patient and dentist satisfaction. Conclusions Platform-switching bone-level implants placed in maxillary single-tooth gaps resulted in successful osseointegration with minimal marginal bone resorption. The peri-implant soft tissue was also esthetically satisfying and stable. PMID:29093988

Sensitivity subgroup analysis based on single-center vs. multi-center trial status when interpreting meta-analyses pooled estimates: the logical way forward.

PubMed

Alexander, Paul E; Bonner, Ashley J; Agarwal, Arnav; Li, Shelly-Anne; Hariharan, Abishek; Izhar, Zain; Bhatnagar, Neera; Alba, Carolina; Akl, Elie A; Fei, Yutong; Guyatt, Gordon H; Beyene, Joseph

2016-06-01

Prior studies regarding whether single-center trial estimates are larger than multi-center are equivocal. We examined the extent to which single-center trials yield systematically larger effects than multi-center trials. We searched the 119 core clinical journals and the Cochrane Database of Systematic Reviews for meta-analyses (MAs) of randomized controlled trials (RCTs) published during 2012. In this meta-epidemiologic study, for binary variables, we computed the pooled ratio of ORs (RORs), and for continuous outcomes mean difference in standardized mean differences (SMDs), we conducted weighted random-effects meta-regression and random-effects MA modeling. Our primary analyses were restricted to MAs that included at least five RCTs and in which at least 25% of the studies used each of single trial center (SC) and more trial center (MC) designs. We identified 81 MAs for the odds ratio (OR) and 43 for the SMD outcome measures. Based on our analytic plan, our primary analysis (core) is based on 25 MAs/241 RCTs (binary outcome) and 18 MAs/173 RCTs (continuous outcome). Based on the core analysis, we found no difference in magnitude of effect between SC and MC for binary outcomes [RORs: 1.02; 95% confidence interval (CI): 0.83, 1.24; I(2) 20.2%]. Effect sizes were systematically larger for SC than MC for the continuous outcome measure (mean difference in SMDs: -0.13; 95% CI: -0.21, -0.05; I(2) 0%). Our results do not support prior findings of larger effects in SC than MC trials addressing binary outcomes but show a very similar small increase in effect in SC than MC trials addressing continuous outcomes. Authors of systematic reviews would be wise to include all trials irrespective of SC vs. MC design and address SC vs. MC status as a possible explanation of heterogeneity (and consider sensitivity analyses). Copyright © 2015 Elsevier Inc. All rights reserved.

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study.

PubMed

Koek, Mayke B G; Buskens, Erik; Steegmans, Paul H A; van Weelden, Huib; Bruijnzeel-Koomen, Carla A F M; Sigurdsson, Vigfús

2006-08-01

Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB phototherapy. Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT00150930.

Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

PubMed

Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

2016-01-01

The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 10(10) viral particle units (pu), 2·5 × 10(10) pu, 5 × 10(10) pu, or 1 × 10(11) pu; US participants received 1 × 10(10) pu or 1 × 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian). Between Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 × 10(10) pu, 35 [38%] to 2·5 × 10(10) pu, 35 [38%] to 5 × 10(10) pu, and 11 [12%] to 1 × 10(11) pu) and 20 in the USA (ten [50%] to 1 × 10(10) pu and ten [50%] to 1 × 10(11) pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 × 10(10) and two [2%] received 1 × 10(11) pu) and four (20%) of 20 in the USA (all received 1 × 10(11) pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness. 1 × 10(11) pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers). Wellcome Trust, Medical Research Council UK, Department for International Development UK, National Cancer Institute, Frederick National Laboratory for Cancer Research, Federal Funds from National Institute of Allergy and Infectious Diseases. Copyright © 2016 Tapia et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Eicosapentaenoic Acid Versus Docosahexaenoic Acid as Options for Vascular Risk Prevention: A Fish Story.

PubMed

Singh, Sarabjeet; Arora, Rohit R; Singh, Mukesh; Khosla, Sandeep

2016-01-01

Vascular inflammation is a key component involved in the process of arthrosclerosis, which in turn increases the risk for cardiovascular injury. In the last 10 years, there have been many trials that looked at omega-3 fatty acids as a way to reduce cardiovascular risk. These trials observed the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the traditional lipid panel and found that both EPA and DHA reduce triglyceride (TG) level and increase high-density lipoprotein cholesterol (HDL-C) levels but also increase the low-density lipoprotein cholesterol (LDL-C) levels. In the 2 more recent trials, the MARINE and ANCHOR, EPA was given as an adjunct therapy to high-risk patients and not only was the traditional lipids measured but also examined the vascular inflammatory biomarkers. The results of these 2 trials not only showed reduction in cardiovascular risk because of reduction in vascular inflammation and reduction in the lipid panel but also showed that one of the MARINE-derived omega-3 fatty acid is superior to the other. Data search for omega-3 fatty acids and cardiovascular risk was performed, and articles were selected for review from 2006 to date. The research studies were all double-blind randomized trials except for one, which was a single-blind and focused on the effects of omega-3 fatty acids on the entire lipid panel. The participants received DHA/EPA and compared with a placebo group on the effect seen in the lipid panel. The first 7 studies looked at the effects of omega-3 fatty acids on TG, LDL-C, and HDL-C; of the 7, 1 directly compared DHA and EPA, 2 focused on EPA, and 4 were directed towards DHA alone. The MARINE and ANCHOR trials were more recent and also looked at the same parameter but also monitored vascular inflammatory biomarkers and how they were affected by omega-3 fatty acids. A second data search was performed for vascular biomarkers and cardiovascular risk, and articles that focused on high-sensitivity C-reactive protein and oxidized low-density lipoprotein were selected for review. Omega-3 fatty acids have shown to decrease TG level in multiple trials, but they have also shown to increase LDL and HDL levels, likely because omega-3 fatty acids promote TG conversion into HDL/LDL. The older data suggested that the benefits of omega-3 fatty acids are nullified by their effects on LDL levels. The data from the MARINE and ANCHOR trials have shown that EPA alone at 4 g per day has shown to decrease TG and total cholesterol without affecting the LDL levels. The earlier data showed that both EPA and DHA decreased TG level and increased levels of HDL-C, but that the DHA alone and direct comparison of DHA/EPA showed that DHA has more undesirable effects on LDL. Furthermore, the MARINE and ANCHOR trials have both shown that not only does EPA improve the lipid panel but also helps to decrease the levels of the vascular inflammatory biomarkers, thus further helping to decrease cardiovascular risk. The use of EPA as an adjunct therapy for high-risk patient has shown to help decrease cardiovascular risk. The reduction in risk is performed not only by decreasing TG but also by reducing vascular inflammation. Although because there are no randomized double-blind study looking at this, the research is inconclusive and requires further investigation.

Influence of platform switching on bone-level alterations: a three-year randomized clinical trial.

PubMed

Enkling, N; Jöhren, P; Katsoulis, J; Bayer, S; Jervøe-Storm, P-M; Mericske-Stern, R; Jepsen, S

2013-12-01

The concept of platform switching has been introduced to implant dentistry based on clinical observations of reduced peri-implant crestal bone loss. However, published data are controversial, and most studies are limited to 12 months. The aim of the present randomized clinical trial was to test the hypothesis that platform switching has a positive impact on crestal bone-level changes after 3 years. Two implants with a diameter of 4 mm were inserted crestally in the posterior mandible of 25 patients. The intraindividual allocation of platform switching (3.3-mm platform) and the standard implant (4-mm platform) was randomized. After 3 months of submerged healing, single-tooth crowns were cemented. Patients were followed up at short intervals for monitoring of healing and oral hygiene. Statistical analysis for the influence of time and platform type on bone levels employed the Brunner-Langer model. At 3 years, the mean radiographic peri-implant bone loss was 0.69 ± 0.43 mm (platform switching) and 0.74 ± 0.57 mm (standard platform). The mean intraindividual difference was 0.05 ± 0.58 mm (95% confidence interval: -0.19, 0.29). Crestal bone-level alteration depended on time (p < .001) but not on platform type (p = .363). The present randomized clinical trial could not confirm the hypothesis of a reduced peri-implant crestal bone loss, when implants had been restored according to the concept of platform switching.

Outpatient 60-hour day-and-night glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or sensor-augmented pump therapy in adults with type 1 diabetes: An open-label, randomised, crossover, controlled trial.

PubMed

Haidar, Ahmad; Messier, Virginie; Legault, Laurent; Ladouceur, Martin; Rabasa-Lhoret, Rémi

2017-05-01

To assess whether the dual-hormone (insulin and glucagon) artificial pancreas reduces hypoglycaemia compared to the single-hormone (insulin alone) artificial pancreas in outpatient settings during the day and night. In a randomized, three-way, crossover trial we compared the dual-hormone artificial pancreas, the single-hormone artificial pancreas and sensor-augmented pump therapy (control) in 23 adults with type 1 diabetes. Each intervention was applied from 8 AM Day 1 to 8 PM Day 3 (60 hours) in outpatient free-living conditions. The primary outcome was time spent with sensor glucose levels below 4.0 mmol/L. A P value of less than .017 was regarded as significant. The median difference between the dual-hormone system and the single-hormone system was -2.3% (P = .072) for time spent below 4.0 mmol/L, -1.3% (P = .017) for time below 3.5 mmol/L, and -0.7% (P = .031) for time below 3.3 mmol/L. Both systems reduced (P < .017) hypoglycaemia below 4.0, 3.5 and 3.3 mmol/L compared to control therapy, but reductions were larger with the dual-hormone system than with the single-hormone system (medians -4.0% vs -3.4% for 4.0 mmol/L; -2.7% vs -2.2% for 3.5 mmol/L; and -2.2% vs -1.2% for 3.3 mmol/L). There were 34 hypoglycaemic events (<3.0 mmol/L for 20 minutes) with control therapy, 14 with the single-hormone system and 6 with the dual-hormone system. These differences in hypoglycaemia were observed while mean glucose level was low and comparable in all interventions (P = NS). The dual-hormone artificial pancreas had the lowest risk of hypoglycaemia, but the differences were not statistically significant. Larger studies are needed. © 2017 John Wiley & Sons Ltd.

A highly sensitive search strategy for clinical trials in Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) was developed.

PubMed

Manríquez, Juan J

2008-04-01

Systematic reviews should include as many articles as possible. However, many systematic reviews use only databases with high English language content as sources of trials. Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) is an underused source of trials, and there is not a validated strategy for searching clinical trials to be used in this database. The objective of this study was to develop a sensitive search strategy for clinical trials in LILACS. An analytical survey was performed. Several single and multiple-term search strategies were tested for their ability to retrieve clinical trials in LILACS. Sensitivity, specificity, and accuracy of each single and multiple-term strategy were calculated using the results of a hand-search of 44 Chilean journals as gold standard. After combining the most sensitive, specific, and accurate single and multiple-term search strategy, a strategy with a sensitivity of 97.75% (95% confidence interval [CI]=95.98-99.53) and a specificity of 61.85 (95% CI=61.19-62.51) was obtained. LILACS is a source of trials that could improve systematic reviews. A new highly sensitive search strategy for clinical trials in LILACS has been developed. It is hoped this search strategy will improve and increase the utilization of LILACS in future systematic reviews.

Effect of surgical periodontal treatment associated to antimicrobial photodynamic therapy on chronic periodontitis: A randomized controlled clinical trial.

PubMed

Martins, Sérgio H L; Novaes, Arthur B; Taba, Mario; Palioto, Daniela B; Messora, Michel R; Reino, Danilo M; Souza, Sérgio L S

2017-07-01

This randomized controlled clinical trial evaluated the effects of an adjunctive single application of antimicrobial photodynamic therapy (aPDT) in Surgical Periodontal Treatment (ST) in patients with severe chronic periodontitis (SCP). In a split-mouth design, 20 patients with SCP were treated with aPDT+ST (Test Group, TG) or ST only (Control Group, CG). aPDT was applied in a single episode, using a diode laser and a phenothiazine photosensitizer. All patients were monitored until 90 days after surgical therapy. Levels of 40 subgingival species were measured by checkerboard DNA-DNA hybridization at baseline, 60 and 150 days. Clinical and microbiological parameters were evaluated. In deep periodontal pockets depth (PPD ≥5 mm), Test Group presented a significantly higher decrease in PPD than Control Group at 90 days after surgical therapy (p < .05). Test Group also demonstrated significantly less periodontal pathogens of red complex (Treponema denticola) (p < .05). A single episode of aPDT used in adjunct to open flap debridement of the root surface in the surgical treatment of SCP: i) significantly improved clinical periodontal parameters; ii) eliminates periodontal pathogens of the red complex more effectively (NCT02734784). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparative study of the efficacy of transdermal buprenorphine patches and prolonged-release tramadol tablets for postoperative pain control after spinal fusion surgery: a prospective, randomized controlled non-inferiority trial.

PubMed

Kim, Ho-Joong; Ahn, Hyo Sae; Nam, Yunjin; Chang, Bong-Soon; Lee, Choon-Ki; Yeom, Jin S

2017-11-01

To compare the efficacy of a transdermal buprenorphine patch (5, 10, 15, and 20 μg/h) with that of oral tramadol (150, 200, 250, and 300 mg) for postoperative pain control after single level spinal fusion surgery. The present study (ClinicalTrials.gov, number NCT02416804) was a prospective, randomized controlled non-inferiority trial designed to determine the efficacy of buprenorphine TDS for alleviating postoperative pain following patient controlled analgesia (PCA) in persons underwent a single level posterior lumbar interbody fusion surgery through 1:1 allocation. The primary outcome was the Visual Analog Pain Scale (VAS) score for postoperative back pain at 7 days after surgery. The non-inferior margin of the VAS was set at δ = 1.5 points. The VAS score (primary outcome) for postoperative back pain at 7 days after surgery in the Buprenorphine group was not inferior compared to the Tramadol group. The overall changes in VAS scores for postoperative pain during follow-up assessments over a 2-week period did not differ between both groups. However, the VAS scores for postoperative pain significantly improved with time after surgery in both groups. The patterns of changes in the VAS scores for postoperative pain during the follow-up period were not significantly different between the both groups. The efficacy of buprenorphine TDS was not inferior to that of oral tramadol medication for alleviating postoperative pain in the subacute period from 72 h after surgery, following PCA administration. In addition, adverse events were similar between both groups.

Polyurethane on titanium unconstrained disc arthroplasty versus anterior discectomy and fusion for the treatment of cervical disc disease: a review of level I-II randomized clinical trials including clinical outcomes.

PubMed

Aragonés, María; Hevia, Eduardo; Barrios, Carlos

2015-12-01

To contrast the clinical and radiologic outcomes and adverse events of anterior cervical discectomy and fusion (ACDF) with a single cervical disc arthroplasty design, the polyurethane on titanium unconstrained cervical disc (PTUCD). This is a systematic review of randomized clinical trials (RCT) with evidence level I-II reporting clinical outcomes. After a search on different databases including PubMed, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE, a total of 10 RCTs out of 51 studies found were entered in the study. RTCs were searched from the earliest available records in 2005 to November 2014. Out of a total of 1101 patients, 562 were randomly assigned into the PTUCD arthroplasty group and 539 into the ACDF group. The mean follow-up was 30.9 months. Patients undergoing arthroplasty had lower Neck Disability Index, and better SF-36 Physical component scores than ACDF patients. Patients with PTUCD arthroplasty had also less radiological degenerative changes at the upper adjacent level. Overall adverse events were twice more frequent in patients with ACDF. The rate of revision surgery including both adjacent and index level was slightly higher in patients with ACDF, showing no statistically significant difference. According to this review, PTUCD arthroplasty showed a global superiority to ACDF in clinical outcomes. The impact of both surgical techniques on the cervical spine (radiological spine deterioration and/or complications) was more severe in patients undergoing ACDF. However, the rate of revision surgeries at any cervical level was equivalent for ACDF and PTUCD arthroplasty.

Trial latencies estimation of event-related potentials in EEG by means of genetic algorithms

NASA Astrophysics Data System (ADS)

Da Pelo, P.; De Tommaso, M.; Monaco, A.; Stramaglia, S.; Bellotti, R.; Tangaro, S.

2018-04-01

Objective. Event-related potentials (ERPs) are usually obtained by averaging thus neglecting the trial-to-trial latency variability in cognitive electroencephalography (EEG) responses. As a consequence the shape and the peak amplitude of the averaged ERP are smeared and reduced, respectively, when the single-trial latencies show a relevant variability. To date, the majority of the methodologies for single-trial latencies inference are iterative schemes providing suboptimal solutions, the most commonly used being the Woody’s algorithm. Approach. In this study, a global approach is developed by introducing a fitness function whose global maximum corresponds to the set of latencies which renders the trial signals most aligned as possible. A suitable genetic algorithm has been implemented to solve the optimization problem, characterized by new genetic operators tailored to the present problem. Main results. The results, on simulated trials, showed that the proposed algorithm performs better than Woody’s algorithm in all conditions, at the cost of an increased computational complexity (justified by the improved quality of the solution). Application of the proposed approach on real data trials, resulted in an increased correlation between latencies and reaction times w.r.t. the output from RIDE method. Significance. The above mentioned results on simulated and real data indicate that the proposed method, providing a better estimate of single-trial latencies, will open the way to more accurate study of neural responses as well as to the issue of relating the variability of latencies to the proper cognitive and behavioural correlates.

Genomic Selection in Multi-environment Crop Trials.

PubMed

Oakey, Helena; Cullis, Brian; Thompson, Robin; Comadran, Jordi; Halpin, Claire; Waugh, Robbie

2016-05-03

Genomic selection in crop breeding introduces modeling challenges not found in animal studies. These include the need to accommodate replicate plants for each line, consider spatial variation in field trials, address line by environment interactions, and capture nonadditive effects. Here, we propose a flexible single-stage genomic selection approach that resolves these issues. Our linear mixed model incorporates spatial variation through environment-specific terms, and also randomization-based design terms. It considers marker, and marker by environment interactions using ridge regression best linear unbiased prediction to extend genomic selection to multiple environments. Since the approach uses the raw data from line replicates, the line genetic variation is partitioned into marker and nonmarker residual genetic variation (i.e., additive and nonadditive effects). This results in a more precise estimate of marker genetic effects. Using barley height data from trials, in 2 different years, of up to 477 cultivars, we demonstrate that our new genomic selection model improves predictions compared to current models. Analyzing single trials revealed improvements in predictive ability of up to 5.7%. For the multiple environment trial (MET) model, combining both year trials improved predictive ability up to 11.4% compared to a single environment analysis. Benefits were significant even when fewer markers were used. Compared to a single-year standard model run with 3490 markers, our partitioned MET model achieved the same predictive ability using between 500 and 1000 markers depending on the trial. Our approach can be used to increase accuracy and confidence in the selection of the best lines for breeding and/or, to reduce costs by using fewer markers. Copyright © 2016 Oakey et al.

Assessment of the anthelmintic efficacy of albendazole in school children in seven countries where soil-transmitted helminths are endemic.

PubMed

Vercruysse, Jozef; Behnke, Jerzy M; Albonico, Marco; Ame, Shaali Makame; Angebault, Cécile; Bethony, Jeffrey M; Engels, Dirk; Guillard, Bertrand; Nguyen, Thi Viet Hoa; Kang, Gagandeep; Kattula, Deepthi; Kotze, Andrew C; McCarthy, James S; Mekonnen, Zeleke; Montresor, Antonio; Periago, Maria Victoria; Sumo, Laurentine; Tchuenté, Louis-Albert Tchuem; Dang, Thi Cam Thach; Zeynudin, Ahmed; Levecke, Bruno

2011-03-29

The three major soil-transmitted helminths (STH) Ascaris lumbricoides, Trichuris trichiura and Necator americanus/Ancylostoma duodenale are among the most widespread parasites worldwide. Despite the global expansion of preventive anthelmintic treatment, standard operating procedures to monitor anthelmintic drug efficacy are lacking. The objective of this study, therefore, was to define the efficacy of a single 400 milligram dose of albendazole (ALB) against these three STH using a standardized protocol. Seven trials were undertaken among school children in Brazil, Cameroon, Cambodia, Ethiopia, India, Tanzania and Vietnam. Efficacy was assessed by the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) using the McMaster egg counting technique to determine fecal egg counts (FEC). Overall, the highest CRs were observed for A. lumbricoides (98.2%) followed by hookworms (87.8%) and T. trichiura (46.6%). There was considerable variation in the CR for the three parasites across trials (country), by age or the pre-intervention FEC (pre-treatment). The latter is probably the most important as it had a considerable effect on the CR of all three STH. Therapeutic efficacies, as reflected by the FECRs, were very high for A. lumbricoides (99.5%) and hookworms (94.8%) but significantly lower for T. trichiura (50.8%), and were affected to different extents among the 3 species by the pre-intervention FEC counts and trial (country), but not by sex or age. Our findings suggest that a FECR (based on arithmetic means) of >95% for A. lumbricoides and >90% for hookworms should be the expected minimum in all future surveys, and that therapeutic efficacy below this level following a single dose of ALB should be viewed with concern in light of potential drug resistance. A standard threshold for efficacy against T. trichiura has yet to be established, as a single-dose of ALB is unlikely to be satisfactory for this parasite. ClinicalTrials.gov NCT01087099.

Multiple Component Event-Related Potential (mcERP) Estimation

NASA Technical Reports Server (NTRS)

Knuth, K. H.; Clanton, S. T.; Shah, A. S.; Truccolo, W. A.; Ding, M.; Bressler, S. L.; Trejo, L. J.; Schroeder, C. E.; Clancy, Daniel (Technical Monitor)

2002-01-01

We show how model-based estimation of the neural sources responsible for transient neuroelectric signals can be improved by the analysis of single trial data. Previously, we showed that a multiple component event-related potential (mcERP) algorithm can extract the responses of individual sources from recordings of a mixture of multiple, possibly interacting, neural ensembles. McERP also estimated single-trial amplitudes and onset latencies, thus allowing more accurate estimation of ongoing neural activity during an experimental trial. The mcERP algorithm is related to informax independent component analysis (ICA); however, the underlying signal model is more physiologically realistic in that a component is modeled as a stereotypic waveshape varying both in amplitude and onset latency from trial to trial. The result is a model that reflects quantities of interest to the neuroscientist. Here we demonstrate that the mcERP algorithm provides more accurate results than more traditional methods such as factor analysis and the more recent ICA. Whereas factor analysis assumes the sources are orthogonal and ICA assumes the sources are statistically independent, the mcERP algorithm makes no such assumptions thus allowing investigators to examine interactions among components by estimating the properties of single-trial responses.

Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

PubMed Central

Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

2016-01-01

Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence). When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence). We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings. Authors' conclusions Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB. PLAIN LANGUAGE SUMMARY Fixed-dose combinations for treating pulmonary tuberculosis What are fixed-dose combinations and how might they improve care of people with tuberculosis Tuberculosis (TB) is an important health problem, especially in developing countries. The treatment for pulmonary TB in new patients includes four oral medicines taken for six months, sometimes as fixed-dose combinations (FDCs) that are combined in one tablet, or taken separately as single-drug formulations. The World Health Organization recommends prescribers use fixed-dose combinations to reduce the number of tablets that people take. On the supply side, this might reduce prescribing errors and improve drug supply efficiency; on the patient's side, FDCS simplify treatment and improve adherence. We conducted a review to assess the efficacy, safety, and acceptability of FDCs compared with single-drug formulations for treating people with newly diagnosed pulmonary TB. What the research says We searched for relevant trials up to 20 November 2015, and included 13 randomized controlled trials that enrolled 5824 people. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. There is probably little or no difference in FDCs compared to single-drug formulations for treatment failure (moderate quality evidence); relapse may be more frequent (low quality evidence); and the number of deaths were similar (moderate quality evidence). There is little or no difference in sputum smear or culture conversion (high quality evidence), and no difference was shown for serious adverse events (moderate quality evidence) or adverse events that led to discontinuation of therapy (low quality evidence). Authors' conclusions We concluded that fixed-dose combinations have similar efficacy to single-drug formulations for treating people with newly diagnosed pulmonary TB. PMID:27186634

Effects of Recent Exposure to a Conditioned Stimulus on Extinction of Pavlovian Fear Conditioning

ERIC Educational Resources Information Center

Chan, Wan Yee Macy; Leung, Hiu T.; Westbrook, R. Frederick; McNally, Gavan P.

2010-01-01

In six experiments we studied the effects of a single re-exposure to a conditioned stimulus (CS; "retrieval trial") prior to extinction training (extinction-reconsolidation boundary) on the development of and recovery from fear extinction. A single retrieval trial prior to extinction training significantly augmented the renewal and reinstatement…

Neural Prediction of Multidimensional Decisions in Monkey Superior Colliculus

NASA Astrophysics Data System (ADS)

Hasegawa, Ryohei P.; Hasegawa, Yukako T.; Segraves, Mark A.

To examine the function of the superior colliculus (SC) in decision-making processes and the application of its single trial activity for “neural mind reading,” we recorded from SC deep layers while two monkeys performed oculomotor go/no-go tasks. We have recently focused on monitoring single trial activities in single SC neurons, and designed a virtual decision function (VDF) to provide a good estimation of single-dimensional decisions (go/no-go decisions for a cue presented at a specific visual field, a response field of each neuron). In this study, we used two VDFs for multidimensional decisions (go/no-go decisions at two cue locations) with the ensemble activity which was simultaneously recorded from a small group (4 to 6) of neurons at both sides of the SC. VDFs predicted cue locations as well as go/no-go decisions. These results suggest that monitoring of ensemble SC activity had sufficient capacity to predict multidimensional decisions on a trial-by-trial basis, which is an ideal candidate to serve for cognitive brain-machine interfaces (BMI) such as two-dimensional word spellers.

Retention of the "first-trial effect" in gait-slip among community-living older adults.

PubMed

Liu, Xuan; Bhatt, Tanvi; Wang, Shuaijie; Yang, Feng; Pai, Yi-Chung Clive

2017-02-01

"First-trial effect" characterizes the rapid adaptive behavior that changes the performance outcome (from fall to non-fall) after merely a single exposure to postural disturbance. The purpose of this study was to investigate how long the first-trial effect could last. Seventy-five (≥ 65 years) community-dwelling older adults, who were protected by an overhead full body harness system, were retested for a single slip 6-12 months after their initial exposure to a single gait-slip. Subjects' body kinematics that was used to compute their proactive (feedforward) and reactive (feedback) control of stability was recorded by an eight-camera motion analysis system. We found the laboratory falls of subjects on their retest slip were significantly lower than that on the novel initial slip, and the reactive stability of these subjects was also significantly improved. However, the proactive stability of subjects remains unchanged between their initial slip and retest slip. The fall rates and stability control had no difference among the 6-, 9-, and 12-month retest groups, which indicated a maximum retention on 12 months after a single slip in the laboratory. These results highlighted the importance of the "first-trial effect" and suggested that perturbation training is effective for fall prevention, with lower trial doses for a long period (up to 1 year). Therefore, single slip training might benefit those older adults who could not tolerate larger doses in reality.

Frontal Theta Links Prediction Errors to Behavioral Adaptation in Reinforcement Learning

PubMed Central

Cavanagh, James F.; Frank, Michael J.; Klein, Theresa J.; Allen, John J.B.

2009-01-01

Investigations into action monitoring have consistently detailed a fronto-central voltage deflection in the Event-Related Potential (ERP) following the presentation of negatively valenced feedback, sometimes termed the Feedback Related Negativity (FRN). The FRN has been proposed to reflect a neural response to prediction errors during reinforcement learning, yet the single trial relationship between neural activity and the quanta of expectation violation remains untested. Although ERP methods are not well suited to single trial analyses, the FRN has been associated with theta band oscillatory perturbations in the medial prefrontal cortex. Medio-frontal theta oscillations have been previously associated with expectation violation and behavioral adaptation and are well suited to single trial analysis. Here, we recorded EEG activity during a probabilistic reinforcement learning task and fit the performance data to an abstract computational model (Q-learning) for calculation of single-trial reward prediction errors. Single-trial theta oscillatory activities following feedback were investigated within the context of expectation (prediction error) and adaptation (subsequent reaction time change). Results indicate that interactive medial and lateral frontal theta activities reflect the degree of negative and positive reward prediction error in the service of behavioral adaptation. These different brain areas use prediction error calculations for different behavioral adaptations: with medial frontal theta reflecting the utilization of prediction errors for reaction time slowing (specifically following errors), but lateral frontal theta reflecting prediction errors leading to working memory-related reaction time speeding for the correct choice. PMID:19969093

Characterizing Oscillatory Bursts in Single-Trial EEG Data

NASA Technical Reports Server (NTRS)

Knuth, K. H.; Shah, A. S.; Lakatos, P.; Schroeder, C. E.

2004-01-01

Oscillatory bursts in numerous bands ranging from low (theta) to high frequencies (e.g., gamma) undoubtedly play an important role in cortical dynamics. Largely because of the inadequacy of existing analytic techniques. however, oscillatory bursts and their role in cortical processing remains poorly understood. To study oscillatory bursts effectively one must be able to isolate them and characterize them in the single trial. We describe a series of straightforward analysis techniques that produce useful indices of burst characteristics. First, stimulus-evoked responses are estimated using Differentially Variable Component Analysis (dVCA), and are subtracted from the single-trial. The single-trial characteristics of the evoked responses are stored to identify possible correlations with burst activity. Time-frequency (T-F), or wavelet, analyses are then applied to the single trial residuals. While T-F plots have been used in recent studies to identify and isolate bursts, we go further by fitting each burst in the T-F plot with a two-dimensional Gaussian. This provides a set of burst characteristics, such as, center time. burst duration, center frequency. frequency dispersion. and amplitude, all of which contribute to the accurate characterization of the individual burst. The burst phase can also be estimated. Burst characteristics can be quantified with several standard techniques (e.g.. histogramming and clustering), as well as Bayesian techniques (e.g., blocking) to allow a more parametric description analysis of the characteristics of oscillatory bursts, and the relationships of specific parameters to cortical excitability and stimulus integration.

How to treat two adjacent missing teeth with dental implants. A systematic review on single implant-supported two-unit cantilever FDP's and results of a 5-year prospective comparative study in the aesthetic zone.

PubMed

Van Nimwegen, W G; Raghoebar, G M; Tymstra, N; Vissink, A; Meijer, H J A

2017-06-01

To conduct a systematic review on the clinical outcome of single implant-supported two-unit cantilever FDP's and to conduct a 5-year prospective comparative pilot study of patients with a missing central and lateral upper incisor treated with either a single implant-supported two-unit cantilever FDP or two implants with solitary implant crowns in the aesthetic zone. Medline, Embase and the Cochrane Central Register of Controlled Trials were searched (last search 1 August 2016) for eligible studies. In the comparative pilot study, an implant-cantilever group of five patients with a single implant-supported two-unit cantilever FDP (NobelReplace Groovy Regular Platform) was compared with an implant-implant group of five patients with two adjacent single implant-supported crowns (NobelReplace Groovy Regular Platform) in the aesthetic zone. Implant survival, marginal bone level (MBL) changes, pocket probing depth, papilla index and patient satisfaction were assessed during a 5-year follow-up period. Five of 276 articles were considered eligible for data extraction. Implant survival ranged from 96·6% to 100%. Marginal bone level changes were higher in the anterior region than in the posterior region. Technical complications occurred more often in the posterior than anterior region. In the 5-year comparative pilot study, no clinically significant differences in hard and soft peri-implant tissue levels occurred between both groups. Single implant-supported two-unit cantilever FDP's can be a viable alternative to the placement of two adjacent single implant crowns in the aesthetic zone. Due to technical complications, placement of two-unit cantilever crowns in the posterior region can be considered unwise. © 2017 John Wiley & Sons Ltd.

Mandibular single-implant overdentures: a review with surgical and prosthodontic perspectives of a novel approach.

PubMed

Alsabeeha, Nabeel; Payne, Alan G T; De Silva, Rohana K; Swain, Michael V

2009-04-01

To review the literature on mandibular single-implant overdentures (opposing complete maxillary dentures), and present surgical and prosthodontic perspectives of a novel approach for this treatment option. An electronic search through the databases of Pubmed, Embase and Medline using the linked key words 'mandibular single implant overdentures' was performed. The search was limited to English language articles published up to August 2008. Hand searches through articles retrieved from the electronic search, peer-reviewed journals and recent conference proceedings were also conducted. A limited number of reports were identified on mandibular single-implant overdentures (opposing maxillary complete dentures). They comprised of case-series reports, short-term prospective trials and current randomized-controlled clinical trials. Different loading protocols with different implant systems have been used, but always with regular diameter implants. Specific anatomical and vascular dangers of the mandibular midline symphysis are identified including a novel surgical approach using a currently available short, wide diameter tapered implant. In addition, the prosthodontic rationale for using a larger attachment system (incorporating a platform switch) for mandibular single-implant overdentures is described. The review reveals that there is a lack of published randomized clinical trials using mandibular single-implant overdentures, opposing maxillary complete dentures. Without the evidence from randomized clinical trials, routine use of this novel approach cannot be recommended, compared with using regular diameter implants and matching attachment systems.

Putting the past behind us: Social stress-induced urinary retention can be overcome.

PubMed

Weiss, Dana A; Butler, Stephan J; Fesi, Joanna; Long, Christopher J; Valentino, Rita J; Canning, Douglas A; Zderic, Stephen A

2015-08-01

To study the pathophysiology of dysfunctional voiding, we have previously developed a model of stress-induced voiding dysfunction. We have shown that cyclosporine A (CsA), an inhibitor of the Ca(2+)-calmodulin complex, can prevent social stress-induced urinary retention. However, treatment with cyclosporine has not had an effect on the increase in the stress peptide corticotrophin-releasing factor (CRF) in Barrington's nucleus, which is involved in the micturition pathway. We now investigate whether cyclosporine administered after stress can reverse the abnormal voiding phenotype, and whether it has effects on the bladder wall itself, or on the stress response within Barrington's nucleus. Six-week old Swiss-Webster mice were exposed to aggressor males for 1 h a day, followed by 23 h of barrier separation. In a long-term trial, 1 month of stress was followed by single-cage housing for 6 months. In a separate CsA reversal trial, mice either received CsA in drinking water or had plain drinking water during 1 month of single-cage housing during recovery. Bladder contractile function was examined on a Guth myograph. Nuclear translocation of myocyte enhancing factor (MEF)-2 and NFAT (nuclear factor of activated T cells) in the bladder was assessed using electrophoretic mobility shift assays (EMSAs). The expression of CRF was determined in Barrington's nucleus using in situ hybridization. Voiding dysfunction persisted for up to 6 months after stress exposure while mice recovered in single-cage housing. In the CsA reversal trial, voiding patterns improved when they received CsA in water during single-cage housing following stress, whereas those that underwent single-cage housing alone had persistent abnormal voiding (Fig. A). There was no difference between CRF levels in Barrington's nucleus between reversal groups (p = 0.42) (Fig. B), possibly indicating a direct effect on the bladder rather than a persistent stress effect. There were no differences in the contractility of bladder wall muscle. CsA decreased the nuclear translocation of MEF-2 and NFAT induced by stress (Fig. C,D). CsA reverses stress-induced urinary retention, but does not change the stress-induced CRF increase in Barrington's nucleus. Furthermore, bladder smooth muscle contractility is unchanged by CsA; however, there are changes in the levels of the downstream transcription factors MEF-2 and NFAT. We suspect that additional CsA responsive neural changes play a pivotal role in the abnormal voiding phenotype following social stress. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Cysteine proteinases from papaya (Carica papaya) in the treatment of experimental Trichuris suis infection in pigs: two randomized controlled trials.

PubMed

Levecke, Bruno; Buttle, David J; Behnke, Jerzy M; Duce, Ian R; Vercruysse, Jozef

2014-05-30

Cysteine proteinases (CPs) from papaya (Carica papaya) possess anthelmintic properties against human soil-transmitted helminths (STH, Ascaris lumbricoides, Trichuris trichiura and hookworm), but there is a lack of supportive and up-to-date efficacy data. We therefore conducted two randomized controlled trials in pigs to assess the efficacy of papaya CPs against experimental infections with T. suis. First, we assessed efficacy by means of egg (ERR) and adult worm reduction rate (WRR) of a single-oral dose of 450 μmol active CPs (CP450) against low (inoculum of 300 eggs) and high (inoculum of 3,000 eggs) intensity T. suis infections and compared the efficacy with those obtained after a single-oral dose of 400 mg albendazole (ALB). In the second trial, we determined and compared the efficacy of a series of CP doses (45 [CP45], 115 [CP115], 225 [CP225], and 450 [CP450] μmol) against high intensity infections. CP450 was highly efficacious against both levels of infection intensity, resulting in ERR and WRR of more than 97%. For both levels of infection intensity, CP450 was significantly more efficacious compared to ALB by means of WRR (low infection intensity: 99.0% vs. 39.0%; high infection intensity; 97.4% vs. 23.2%). When the efficacy was assessed by ERR, a significant difference was only observed for high intensity infections, CP450 being more efficacious than ALB (98.9% vs. 59.0%). For low infection intensities, there was no significant difference in ERR between CP450 (98.3%) and ALB (64.4%). The efficacy of CPs increased as a function of increasing dose. When determined by ERR, the efficacy ranged from 2.1% for CP45 to 99.2% for CP450. For WRR the results varied from -14.0% to 99.0%, respectively. Pairwise comparison revealed a significant difference in ERR and WRR only between CP45 and CP450, the latter being more efficacious. A single dose of 450 μmol CPs provided greater efficacy against T. suis infections in pigs than a single-oral dose of 400 mg ALB. Although these results highlight the possibility of papaya CPs for controlling human STH, further development is needed in order to obtain and validate an oral formulation for human application.

Spontaneous Recovery After Extinction of the Conditioned Proboscis Extension Response in the Honeybee

PubMed Central

Sandoz, Jean-Christophe; Pham-Delègue, Minh-Hà

2004-01-01

In honeybees, the proboscis extension response (PER) can be conditioned by associating an odor stimulus (CS) to a sucrose reward (US). Conditioned responses to the CS, which are acquired by most bees after a single CS-US pairing, disappear after repeated unrewarded presentations of the CS, a process called extinction. Extinction is usually thought to be based either on (1) the disruption of the stored CS-US association, or (2) the formation of an inhibitory “CS-no US” association that is better retrieved than the initial CS-US association. The observation of spontaneous recovery, i.e., the reappearance of responses to the CS after time passes following extinction, is traditionally interpreted as a proof for the formation of a transient inhibitory association. To provide a better understanding of extinction in honeybees, we examined whether time intervals during training and extinction or the number of conditioning and extinction trials have an effect on the occurrence of spontaneous recovery. We found that spontaneous recovery mostly occurs when conditioning and testing took place in a massed fashion (1-min intertrial intervals). Moreover, spontaneous recovery depended on the time elapsed since extinction, 1 h being an optimum. Increasing the number of conditioning trials improved the spontaneous recovery level, whereas increasing the number of extinction trials reduced it. Lastly, we show that after single-trial conditioning, spontaneous recovery appears only once after extinction. These elements suggest that in honeybees extinction of the PER actually reflects the impairment of the CS-US association, but that depending on training parameters different memory substrates are affected. PMID:15466313

Mindfulness-based Intervention for Female Adolescents with Chronic Pain: A Pilot Randomized Trial

PubMed Central

Chadi, Nicholas; McMahon, Audrey; Vadnais, Majorie; Malboeuf-Hurtubise, Catherine; Djemli, Anissa; Dobkin, Patricia L.; Lacroix, Jacques; Luu, Thuy Mai; Haley, Nancy

2016-01-01

Objective To test the feasibility of a randomized-controlled trial measuring the impact of an adapted mindfulness-based intervention (MBI) in female adolescents with chronic pain. Methods This was a single center, single-blind, prospective, experimental, longitudinal trial conducted in a pediatric tertiary care center. Participants had a history of chronic pain during at least three months. They were randomized into an intervention group or a wait-list control group. Both groups successively followed an adapted eight-week MBI designed specifically for adolescents with chronic pain. Pre-determined criteria were established to assess the feasibility, validity and acceptability of the study model. Data evaluating changes in quality of life, depression, anxiety, pain perception, psychological distress and salivary cortisol were collected throughout the 4-month study period. Results Nineteen female participants completed the study and had a mean age of 15.8 years (range 13.9 -17.8). Attrition rate was low (17%). Attendance to mindfulness sessions (84%) and compliance to study protocol (100%) were high. All participants reported a positive change in the way they coped with pain. No changes in quality of life, depression, anxiety, pain perception, and psychological distress were detected. Significant reductions in pre-and post-mindfulness session salivary cortisol levels were observed (p<0.001). Conclusions Mindfulness is a promising therapeutic approach for which limited data exist in adolescents with chronic pain. Our study indicates the feasibility of conducting such interventions in teenage girls. A large trial is needed to demonstrate the efficacy and bio-physiological impacts of MBIs in teenagers with chronic pain. PMID:27924146

Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.

PubMed

Dorigatti, Ilaria; Aguas, Ricardo; Donnelly, Christl A; Guy, Bruno; Coudeville, Laurent; Jackson, Nicholas; Saville, Melanie; Ferguson, Neil M

2015-07-17

The most advanced dengue vaccine candidate is a live-attenuated recombinant vaccine containing the four dengue viruses on the yellow fever vaccine backbone (CYD-TDV) developed by Sanofi Pasteur. Several analyses have been published on the safety and immunogenicity of the CYD-TDV vaccine from single trials but none modelled the heterogeneity observed in the antibody responses elicited by the vaccine. We analyse the immunogenicity data collected in five phase-2 trials of the CYD-TDV vaccine. We provide a descriptive analysis of the aggregated datasets and fit the observed post-vaccination PRNT50 titres against the four dengue (DENV) serotypes using multivariate regression models. We find that the responses to CYD-TDV are principally predicted by the baseline immunological status against DENV, but the trial is also a significant predictor. We find that the CYD-TDV vaccine generates similar titres against all serotypes following the third dose, though DENV4 is immunodominant after the first dose. This study contributes to a better understanding of the immunological responses elicited by CYD-TDV. The recent availability of phase-3 data is a unique opportunity to further investigate the immunogenicity and efficacy of the CYD-TDV vaccine, especially in subjects with different levels of pre-existing immunity against DENV. Modelling multiple immunological outcomes with a single multivariate model offers advantages over traditional approaches, capturing correlations between response variables, and the statistical method adopted in this study can be applied to a variety of infections with interacting strains. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Efficacy and safety of electroacupuncture in acute decompensated heart failure: a study protocol for a randomized, patient- and assessor-blinded, sham controlled trial.

PubMed

Leem, Jungtae; Lee, Seung Min Kathy; Park, Jun Hyeong; Lee, Suji; Chung, Hyemoon; Lee, Jung Myung; Kim, Weon; Lee, Sanghoon; Woo, Jong Shin

2017-07-11

The purpose of this trial is to evaluate the effectiveness and safety of electroacupuncture in the treatment of acute decompensated heart failure compared with sham electroacupuncture. This protocol is for a randomized, sham controlled, patient- and assessor-blinded, parallel group, single center clinical trial that can overcome the limitations of previous trials examining acupuncture and heart failure. Forty-four acute decompensated heart failure patients admitted to the cardiology ward will be randomly assigned into the electroacupuncture treatment group (n = 22) or the sham electroacupuncture control group (n = 22). Participants will receive electroacupuncture treatment for 5 days of their hospital stay. The primary outcome of this study is the difference in total diuretic dose between the two groups during hospitalization. On the day of discharge, follow-up heart rate variability, routine blood tests, cardiac biomarkers, high-sensitivity C-reactive protein (hs-CRP) level, and N-terminal pro b-type natriuretic peptide (NT-pro BNP) level will be assessed. Four weeks after discharge, hs-CRP, NT-pro BNP, heart failure symptoms, quality of life, and a pattern identification questionnaire will be used for follow-up analysis. Six months after discharge, major cardiac adverse events and cardiac function measured by echocardiography will be assessed. Adverse events will be recorded during every visit. The result of this clinical trial will offer evidence of the effectiveness and safety of electroacupuncture for acute decompensated heart failure. Clinical Research Information Service: KCT0002249 .

Efficacy of umbilical cord cleansing with a single application of 4% chlorhexidine for the prevention of newborn infections in Uganda: study protocol for a randomized controlled trial.

PubMed

Nankabirwa, Victoria; Tylleskär, Thorkild; Tumuhamye, Josephine; Tumwine, James K; Ndeezi, Grace; Martines, José C; Sommerfelt, Halvor

2017-07-12

Yearly, nearly all the estimated worldwide 2.7 million neonatal deaths occur in low- and middle-income countries. Infections, including those affecting the umbilical cord (omphalitis), are a significant factor in approximately a third of these deaths. In fact, the odds of all-cause mortality are 46% higher among neonates with omphalitis than in those without. Five large randomized controlled trials in Asia and Sub-Saharan Africa (SSA) have examined the effect of multiple cord stump applications with 4% chlorhexidine (CHX) for at least 7 days on the risk of omphalitis and neonatal death. These studies, all community-based, show that multiple CHX applications reduced the risk of omphalitis. Of these trials, only one study from South Asia (the Bangladeshi study) and none from Africa examined the effect of a single application of CHX as soon as possible after birth. In this Bangladeshi trial, CHX led to a reduction in the risk of mild-moderate omphalitis and neonatal death. It is important, in an African setting, to explore the effect of a single application among health-facility births. A single application is programmatically much simpler to implement than daily applications for 7 days. Therefore, our study compares umbilical cord cleansing with a single application of 4% CHX at birth with dry cord care among Ugandan babies born in health facilities, on the risk of omphalitis and severe neonatal illness. The CHX study is a facility-based, individually randomized controlled trial that will be conducted among 4760 newborns in Uganda. The primary outcomes are severe illness and omphalitis during the neonatal period. Analysis will be by intention-to-treat. This study will provide novel evidence, from a Sub-Saharan African setting, of the effect of umbilical cord cleansing with a single application of 4% CHX at birth and identify modifiable risk factors for omphalitis. ClinicalTrials.gov, identifier: NCT02606565 . Registered on 12 November 2015.

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

PubMed Central

Tsao, May N.; Rades, Dirk; Wirth, Andrew; Lo, Simon S.; Danielson, Brita L.; Gaspar, Laurie E.; Sperduto, Paul W.; Vogelbaum, Michael A.; Radawski, Jeffrey D.; Wang, Jian Z.; Gillin, Michael T.; Mohideen, Najeeb; Hahn, Carol A.; Chang, Eric L.

2012-01-01

Purpose To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Conclusions Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone). PMID:25925626

Effectiveness of acarbose in treating elderly patients with diabetes with postprandial hypotension.

PubMed

Zhang, Jie; Guo, Lixin

2017-04-01

: Postprandial hypotension (PPH) is a common condition that occurs primarily in elderly patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness of acarbose for PPH; it also investigated possible mechanisms behind PPH development. This single-blind, randomized controlled trial included 91 elderly patients with T2DM, aged between 60 and 80 years, who were inpatients at Beijing Hospital between March 2012 and November 2014. The patients were included into one of three groups: Group A, patients with T2DM without PPH; Group B, patients with T2DM with PPH receiving placebo; and Group C, patients with T2DM with PPH receiving acarbose. After an overnight fast, patients received a single dose of acarbose (100 mg) or placebo and then consumed a standardized 450 kcal meal. Blood pressure, glucose levels, heart rate (HR), and catecholamine levels were evaluated. Acarbose ameliorated PPH as determined by significant improvements in the duration and maximal fall in blood pressure (both p<0.001); however, no differences in HR and blood glucose levels were observed. In patients with PPH, blood pressure was correlated with blood glucose and HR variability values (p<0.05). Correlations between epinephrine and glucagon-like peptide-1 with blood pressure in groups A and C were largely lost in group B. Acarbose reduced postprandial blood pressure fluctuations in elderly patients with diabetes. PPH may be related to impaired autonomic nervous system function, reduced catecholamine secretion, and postprandial fluctuations in blood glucose levels. Chinese Clinical Trial Registry ChiCTR-IPR-15006177. Copyright © 2017 American Federation for Medical Research.

A RCT comparing 7-year clinical outcomes of one level symptomatic cervical disc disease (SCDD) following ProDisc-C total disc arthroplasty (TDA) versus anterior cervical discectomy and fusion (ACDF).

PubMed

Loumeau, Thomas P; Darden, Bruce V; Kesman, Thomas J; Odum, Susan M; Van Doren, Bryce A; Laxer, Eric B; Murrey, Daniel B

2016-07-01

The objective of this trial was to compare the safety and efficacy of TDA using the ProDisc-C implant to ACDF in patients with single-level SCDD between C3 and C7. We report on the single-site results from a larger multicenter trial of 13 sites using an approved US Food and Drug Administration protocol (prospective, randomized controlled non-inferiority design). Patients were randomized one-to-one to either the ProDisc-C device or ACDF. All enrollees were evaluated pre- and post-operatively at regular intervals through month 84. Visual Analog Scale (VAS) for neck and arm pain/intensity, Neck Disability Index (NDI), Short-Form 36 (SF-36), and satisfaction were assessed. Twenty-two patients were randomized to each arm of the study. Nineteen additional patients received the ProDisc-C via continued access. NDI improved with the ProDisc-C more than with ACDF. Total range of motion was maintained with the ProDisc-C, but diminished with ACDF. Neck and arm pain improved more in the ProDisc-C than ACDF group. Patient satisfaction remained higher in the ProDisc-C group at 7 years. SF-36 scores were higher in the TDA group than ACDF group at 7 years; the difference was not clinically significant. Six additional operations (two at the same level; four at an adjacent level) were performed in the ACDF, but none in the ProDisc-C group. The ProDisc-C implant appears to be safe and effective for the treatment of SCDD. Patients with the implant retained motion at the involved segment and had a lower reoperation rate than those with an ACDF.

Single Versus Multiple Events Error Potential Detection in a BCI-Controlled Car Game With Continuous and Discrete Feedback.

PubMed

Kreilinger, Alex; Hiebel, Hannah; Müller-Putz, Gernot R

2016-03-01

This work aimed to find and evaluate a new method for detecting errors in continuous brain-computer interface (BCI) applications. Instead of classifying errors on a single-trial basis, the new method was based on multiple events (MEs) analysis to increase the accuracy of error detection. In a BCI-driven car game, based on motor imagery (MI), discrete events were triggered whenever subjects collided with coins and/or barriers. Coins counted as correct events, whereas barriers were errors. This new method, termed ME method, combined and averaged the classification results of single events (SEs) and determined the correctness of MI trials, which consisted of event sequences instead of SEs. The benefit of this method was evaluated in an offline simulation. In an online experiment, the new method was used to detect erroneous MI trials. Such MI trials were discarded and could be repeated by the users. We found that, even with low SE error potential (ErrP) detection rates, feasible accuracies can be achieved when combining MEs to distinguish erroneous from correct MI trials. Online, all subjects reached higher scores with error detection than without, at the cost of longer times needed for completing the game. Findings suggest that ErrP detection may become a reliable tool for monitoring continuous states in BCI applications when combining MEs. This paper demonstrates a novel technique for detecting errors in online continuous BCI applications, which yields promising results even with low single-trial detection rates.

Relationship between post-extraction pain and acute pulpitis: a randomised trial using third molars.

PubMed

Zhang, Wei; Dai, Yong-Bo; Wan, Peng-Cheng; Xu, Dong-Dong; Guo, Yi; Li, Zhi

2016-12-01

The aim of the present study was to examine the relationship between post-extraction pain and acute pulpitis in third molars. This study was a randomised controlled trial. Sixty patients requiring removal of a single maxillary third molar with acute pulpitis were included and randomly divided into two groups: group A (n = 30); and group B (n = 30). In group A, third molars were directly extracted, and group B received endodontic therapy (pulp chamber opening and drainage) and underwent extraction 24 hours later, aiming to eliminate the acute inflammation. Another 30 patients requiring removal of a single maxillary third molar and with the same inclusion criteria but without caries or acute pulpitis were recruited into group C, in which the maxillary third molars were also directly extracted. The level of postoperative pain reported each day among the three groups was statistically evaluated. On the first, second and third days after surgery, there was a statistically significant difference between group A and group B and between group A and group C, but there was no statistically significant difference between group B and group C. The results of the present study indicate that there is more pain when third molars with acute pulpitis are directly removed compared with the pain level of the removal of third molars without acute pulpitis. © 2016 FDI World Dental Federation.

Preemptive Use of Naproxen on Tooth Sensitivity Caused by In-Office Bleaching: A Triple-Blind, Crossover, Randomized Clinical Trial.

PubMed

Fernandes, M T; Vaez, S C; Lima, C M; Nahsan, F P; Loguércio, A D; Faria-E-Silva, A L

A triple-blind, randomized, crossover clinical trial evaluated prior use of nonsteroidal anti-inflammatory naproxen on sensitivity reported by patients undergoing in-office tooth bleaching. Fifty patients were subjected to two sessions of in-office tooth bleaching with 35% hydrogen peroxide in a single application of 40 minutes for two sessions, with an interval of seven days between applications. One hour prior to the procedure, each patient randomly received a single dose of naproxen (500 mg) or placebo. The patient's sensitivity level was evaluated during and immediately after the bleaching using two scales (verbal and visual analog); the verbal scale only was repeated after 24 hours. The effectiveness of the bleaching procedures was evaluated with the Bleachedguide scale. Relative risk to sensitivity was calculated and adjusted by session, while comparison of overall risk was performed by the McNemar test. Data on the sensitivity level for both scales and shade were subjected to the Friedman, Wilcoxon, and Mann-Whitney tests (α=0.05). The use of naproxen only decreased the absolute risk and intensity of tooth sensitivity reported immediately after the second session. On the other hand, no measurable effect was observed during or 24 hours after either session. The sequence of drug administration did not affect the bleaching effectiveness. Preemptive use of naproxen only reduced tooth sensitivity reported by patients immediately after the second session of bleaching.

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

PubMed

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

2017-02-01

Single-tooth replacement often requires a prefabricated dental implant and a customized crown. The benefits of individualization of the abutment remain unclear. This randomized controlled clinical trial aims to study potential benefits of individualization of zirconia implant abutments with respect to preservation of marginal bone level and several clinical and patient-based outcome measures. Fifty participants with a missing premolar were included and randomly assigned to standard (ZirDesign, DentsplySirona Implants, Mölndal, Sweden) or computer aided design/computer aided manufacturing (CAD/CAM) customized (Atlantis, DentsplySirona Implants, Mölndal, Sweden) zirconia abutment therapy. Peri-implant bone level (primary outcome), Plaque-index, calculus formation, bleeding on probing, gingiva index, probing pocket depth, recession, appearance of soft tissues and patients' contentment were assessed shortly after placement and one year later. No implants were lost and no complications related to the abutments were observed. Statistically significant differences between stock and CAD/CAM customized zirconia abutments could not be demonstrated for any of the operationalized variables. The use of a CAD/CAM customized zirconia abutment in single tooth replacement of a premolar is not associated with an improvement in clinical performance or patients' contentment when compared to the use of a stock zirconia abutment. © 2016 The Authors. Clinical Implant Dentistry and Related Research Published by Wiley Periodicals, Inc.

Removal of BCG artifacts using a non-Kirchhoffian overcomplete representation.

PubMed

Dyrholm, Mads; Goldman, Robin; Sajda, Paul; Brown, Truman R

2009-02-01

We present a nonlinear unmixing approach for extracting the ballistocardiogram (BCG) from EEG recorded in an MR scanner during simultaneous acquisition of functional MRI (fMRI). First, an overcomplete basis is identified in the EEG based on a custom multipath EEG electrode cap. Next, the overcomplete basis is used to infer non-Kirchhoffian latent variables that are not consistent with a conservative electric field. Neural activity is strictly Kirchhoffian while the BCG artifact is not, and the representation can hence be used to remove the artifacts from the data in a way that does not attenuate the neural signals needed for optimal single-trial classification performance. We compare our method to more standard methods for BCG removal, namely independent component analysis and optimal basis sets, by looking at single-trial classification performance for an auditory oddball experiment. We show that our overcomplete representation method for removing BCG artifacts results in better single-trial classification performance compared to the conventional approaches, indicating that the derived neural activity in this representation retains the complex information in the trial-to-trial variability.

Single-trial analysis of the neural correlates of speech quality perception.

PubMed

Porbadnigk, Anne K; Treder, Matthias S; Blankertz, Benjamin; Antons, Jan-Niklas; Schleicher, Robert; Möller, Sebastian; Curio, Gabriel; Müller, Klaus-Robert

2013-10-01

Assessing speech quality perception is a challenge typically addressed in behavioral and opinion-seeking experiments. Only recently, neuroimaging methods were introduced, which were used to study the neural processing of quality at group level. However, our electroencephalography (EEG) studies show that the neural correlates of quality perception are highly individual. Therefore, it became necessary to establish dedicated machine learning methods for decoding subject-specific effects. The effectiveness of our methods is shown by the data of an EEG study that investigates how the quality of spoken vowels is processed neurally. Participants were asked to indicate whether they had perceived a degradation of quality (signal-correlated noise) in vowels, presented in an oddball paradigm. We find that the P3 amplitude is attenuated with increasing noise. Single-trial analysis allows one to show that this is partly due to an increasing jitter of the P3 component. A novel classification approach helps to detect trials with presumably non-conscious processing at the threshold of perception. We show that this approach uncovers a non-trivial confounder between neural hits and neural misses. The combined use of EEG signals and machine learning methods results in a significant 'neural' gain in sensitivity (in processing quality loss) when compared to standard behavioral evaluation; averaged over 11 subjects, this amounts to a relative improvement in sensitivity of 35%.

A MISO-ARX-Based Method for Single-Trial Evoked Potential Extraction.

PubMed

Yu, Nannan; Wu, Lingling; Zou, Dexuan; Chen, Ying; Lu, Hanbing

2017-01-01

In this paper, we propose a novel method for solving the single-trial evoked potential (EP) estimation problem. In this method, the single-trial EP is considered as a complex containing many components, which may originate from different functional brain sites; these components can be distinguished according to their respective latencies and amplitudes and are extracted simultaneously by multiple-input single-output autoregressive modeling with exogenous input (MISO-ARX). The extraction process is performed in three stages: first, we use a reference EP as a template and decompose it into a set of components, which serve as subtemplates for the remaining steps. Then, a dictionary is constructed with these subtemplates, and EPs are preliminarily extracted by sparse coding in order to roughly estimate the latency of each component. Finally, the single-trial measurement is parametrically modeled by MISO-ARX while characterizing spontaneous electroencephalographic activity as an autoregression model driven by white noise and with each component of the EP modeled by autoregressive-moving-average filtering of the subtemplates. Once optimized, all components of the EP can be extracted. Compared with ARX, our method has greater tracking capabilities of specific components of the EP complex as each component is modeled individually in MISO-ARX. We provide exhaustive experimental results to show the effectiveness and feasibility of our method.

Combining features from ERP components in single-trial EEG for discriminating four-category visual objects.

PubMed

Wang, Changming; Xiong, Shi; Hu, Xiaoping; Yao, Li; Zhang, Jiacai

2012-10-01

Categorization of images containing visual objects can be successfully recognized using single-trial electroencephalograph (EEG) measured when subjects view images. Previous studies have shown that task-related information contained in event-related potential (ERP) components could discriminate two or three categories of object images. In this study, we investigated whether four categories of objects (human faces, buildings, cats and cars) could be mutually discriminated using single-trial EEG data. Here, the EEG waveforms acquired while subjects were viewing four categories of object images were segmented into several ERP components (P1, N1, P2a and P2b), and then Fisher linear discriminant analysis (Fisher-LDA) was used to classify EEG features extracted from ERP components. Firstly, we compared the classification results using features from single ERP components, and identified that the N1 component achieved the highest classification accuracies. Secondly, we discriminated four categories of objects using combining features from multiple ERP components, and showed that combination of ERP components improved four-category classification accuracies by utilizing the complementarity of discriminative information in ERP components. These findings confirmed that four categories of object images could be discriminated with single-trial EEG and could direct us to select effective EEG features for classifying visual objects.

Comparison of Single Intra-Articular Injection of Novel Hyaluronan (HYA-JOINT Plus) with Synvisc-One for Knee Osteoarthritis: A Randomized, Controlled, Double-Blind Trial of Efficacy and Safety.

PubMed

Sun, Shu-Fen; Hsu, Chien-Wei; Lin, Huey-Shyan; Liou, I-Hsiu; Chen, Yin-Han; Hung, Chia-Ling

2017-03-15

Viscosupplementation has been widely used for the treatment of knee osteoarthritis. Because we found no well-controlled trial comparing single-injection regimens of hyaluronan for knee osteoarthritis, we compared the efficacy and safety of a single intra-articular injection of a novel cross-linked hyaluronan (HYA-JOINT Plus) with a single injection of Synvisc-One in patients with knee osteoarthritis. In a prospective, randomized, controlled, double-blind trial with a 6-month follow-up, 132 patients with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) were randomized to receive 1 intra-articular injection of 3 mL of HYA-JOINT Plus (20 mg/mL) (n = 66) or 6 mL of Synvisc-One (8 mg/mL) (n = 66). The primary outcome was the change from baseline in the visual analog scale (VAS) (0 to 100 mm) pain score at 6 months. Secondary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, Likert scale), Lequesne index, timed "Up & Go" (TUG) test, single-limb stance (SLS) test, use of rescue analgesics, and patient satisfaction. A total of 121 patients were available for the intention-to-treat analysis at 6 months. Both groups had a significant improvement in the VAS, WOMAC, and Lequesne index scores at each follow-up visit (p < 0.001). Patients who received HYA-JOINT Plus experienced a significantly greater improvement in the VAS pain score at 1, 3, and 6 months compared with those treated with Synvisc-One (adjusted mean difference: -12.0, -8.5, and -6.6; p = 0.001, 0.033, and 0.045, respectively). There were no significant between-group differences in any of the secondary outcomes except the WOMAC stiffness scores at 6 months, which favored HYA-JOINT Plus treatment (p = 0.043). The TUG time did not change significantly in either group during the study (p > 0.05), but the SLS time improved significantly in both the HYA-JOINT Plus and the Synvisc-One group (p = 0.004 and p = 0.022, respectively). No significant between-group differences were observed with respect to patient satisfaction or consumption of analgesics. No serious adverse events occurred following the injections. A single injection of either HYA-JOINT Plus or Synvisc-One is safe and effective for 6 months in patients with knee osteoarthritis. HYA-JOINT Plus is superior to Synvisc-One in terms of reducing the VAS pain score at 1, 3, and 6 months and the WOMAC stiffness score at 6 months, with similar safety. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints.

PubMed

Renfro, Lindsay A; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J

2014-10-01

Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer.

Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints

PubMed Central

Renfro, Lindsay A.; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J.

2014-01-01

Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer. PMID:25061255

Single vs two implant-retained overdentures for edentulous mandibles: a systematic review.

PubMed

Alqutaibi, Ahmed Yaseen; Esposito, Marco; Algabri, Radwan; Alfahad, Adnan; Kaddah, Amal; Farouk, Mohammed; Alsourori, Ali

To compare prosthesis and implant failure, patient satisfaction, prosthetic complications and peri-implant marginal bone loss of mandibular overdentures (IOD) supported by a single or two implants. Manual and electronic database (PubMed and Cochrane) searches were performed to identify randomised controlled trials, without language restriction, comparing single vs two implant supported mandibular overdentures. Two investigators extracted data independently. The Cochrane tool was used for assessing the quality of included studies. Meta-analyses were performed for the included RCTs. Six publications corresponding to four RCTs were identified. Three RCTs (corresponding to five publications) were included and one trial was excluded. Follow-ups in function were 1, 3 and 5 years after loading. All included studies were considered to be at a high risk of bias. The pooled result revealed more prosthesis failures at overdentures supported by two implants at 1 year (three trials) (P = 0.02; Risk Difference: -0.12, 95% CI: -0.22, -0.02), however, there were non-significant differences at 3 years (two trials) (P = 0.22; Risk Difference: -0.32, 95% CI: -0.83, 0.19) and at 5 years (one trial) (P = 0.95; Risk Difference: 0.01, 95% CI: -0.22, 0.24). Regarding implant failures, there were more implant losses in overdentures supported by two implants at 1 year (three trials) (P = 0.02; Risk Difference: -0.12, 95% CI: -0.22, -0.02) and at 5 years (one trial) (P = 0.95; Risk Difference: -0.15, 95% CI: -0.28, -0.02), however, there were non-significant difference at 3 years (two trials) (P = 0.2; Risk Difference: -0.33, 95% CI: -0.84, 0.18). After 5 years in function, meta-analyses revealed that there were non-significant differences regarding overall prosthetic complications when mandibular overdentures supported by a single implant were compared with overdentures supported by two implants (P = 0.43; RD: 0.04, 95% CI: -0.06, 0.15). Mandibular overdentures retained by a single implant have comparable results to those retained by two implants. However, this should be interpreted with caution as all the included studies were considered at a high risk of bias.

Associative Interference and Recognition Memory.

ERIC Educational Resources Information Center

Underwood, Benton J.; And Others

Three experiments tested the generality of the conclusion that associative unlearning is minimal in the A-B, A-D paradigm. In Experiment 1, single-trial study of A-D, following single-trial study of A-B, did not produce retroactive inhibition in the recognition of A-B. In Experiment 2, A-B was acquired by associative matching. The interpolated…

Weakening of ion-channel interactions of Na+ and Li+ in acetylcholine-receptor channels of frog skeletal muscle with an increase in agonist concentration.

PubMed

Manthey, A A

1998-05-01

The possibility that increases in agonist concentration beyond threshold levels may force changes in the character of high-conductance open states of skeletal muscle nicotinic acetylcholine receptor channels (nAChR) was examined by seeing whether differences in several critical ionic properties of nAChR currents could be detected with changes in agonist level. Single- and bi-ionic whole-cell currents of Na+ and Li+ in voltage-clamped frog (Rana pipiens) muscle fibers were measured during local superfusion of endplates with carbamylcholine (carb) at concentrations of 54 microm (low-carb) and 270 microM (high-carb). Three ionic properties that would be affected by changes in the open-state configuration of channel subunits were tested. First, ion-saturation characteristics. Peak Na+ and Li+ currents in low-carb trials showed sublinear dependence on ion concentrations from 0 to 60 mM with Km values of 78 (Na+) and 49 (Li+) mM and a power function slope of 0. 75 on double-log plot. In contrast, the concentration dependence of Na+ and Li+ currents in high-carb tests was linear through the origin with a power function slope of 1.02. Second, Na+/Li+ selectivity. The ratio of peak Na+ and Li+ currents in low-carb tests varied from 1.86 to 2.28 for ion concentrations of from 20 to 60 mM [mean = 2.02 +/- 0.06 (SEM)] whereas the ratio for high-carb trials ranged from only 1.29 to 1.52 [mean = 1.42 +/- 0.40 (SEM)]. Third, competitive interactions of Na+ and Li+ currents. Equimolar mixtures of Na+ and Li+ in low-carb tests produced bi-ionic inward currents which were never larger than the single-ion Na+ current alone, but bi-ionic currents at the high-carb level were always greater than the single-ion Na+ current, approximating the sum of the single-ion Na+ and Li+ currents in most cases. The results are consistent with a decrease in ion-channel binding at the high-carb level and support the possibility of agonist-induced changes in the high-conductance open-state configuration of nAChR subunits which result in a weakening of constraints on cation movements through the channel.

Are multiple-trial experiments appropriate for eyewitness identification studies? Accuracy, choosing, and confidence across trials.

PubMed

Mansour, J K; Beaudry, J L; Lindsay, R C L

2017-12-01

Eyewitness identification experiments typically involve a single trial: A participant views an event and subsequently makes a lineup decision. As compared to this single-trial paradigm, multiple-trial designs are more efficient, but significantly reduce ecological validity and may affect the strategies that participants use to make lineup decisions. We examined the effects of a number of forensically relevant variables (i.e., memory strength, type of disguise, degree of disguise, and lineup type) on eyewitness accuracy, choosing, and confidence across 12 target-present and 12 target-absent lineup trials (N = 349; 8,376 lineup decisions). The rates of correct rejections and choosing (across both target-present and target-absent lineups) did not vary across the 24 trials, as reflected by main effects or interactions with trial number. Trial number had a significant but trivial quadratic effect on correct identifications (OR = 0.99) and interacted significantly, but again trivially, with disguise type (OR = 1.00). Trial number did not significantly influence participants' confidence in correct identifications, confidence in correct rejections, or confidence in target-absent selections. Thus, multiple-trial designs appear to have minimal effects on eyewitness accuracy, choosing, and confidence. Researchers should thus consider using multiple-trial designs for conducting eyewitness identification experiments.

Role of Omega-3 Fatty Acids on Lipid Profile in Diabetic Dyslipidaemia: Single Blind, Randomised Clinical Trial.

PubMed

Chauhan, Shaylika; Kodali, Hanish; Noor, Jawad; Ramteke, Karuna; Gawai, Vidisha

2017-03-01

Diabetic dyslipidaemia is characterised by hypertriglyceridaemia, low High Density Lipoprotein (HDL), postprandial lipimea, small and dense LDL particles is considered to be a major predisposing factor for various macrovascular complications. Omega-3 fatty acids are fish oil derivative introduced in the market for dyslipidaemia associated with increased triglyceride level. To study the effect of omega-3 fatty acids on lipid profile in Type II diabetes patients. This study was prospective, single blind, randomized comparative trial. Hundred patients were randomized into three groups. Group I received metformin 500 mg twice daily and placebo, Group II received metformin 500 mg twice daily and omega-3 fatty acids (1 gram) once daily and the Group III received metformin 500 mg twice daily and omega-3 fatty acids (1 gram) twice daily. ANOVA test was applied for analysis. Group II was effective in reducing the triglyceride level from 144.59±14.18 mg/dl to 101±13.31 mg/dl which was significant as compared to Group I from 147.67±18.57 mg/dl to 145.8±19.86 mg/dl respectively. Group III containing 1 g of omega-3 fatty acids twice daily showed decrease from 144.83±22.17 mg/dl to 86±17.46 mg/dl and was more effective in reducing triglyceride levels than Group II containing 1 gram of omega-3 fatty acids once daily. Omega-3 fatty acids can be given in conjunction with metformin to reduce triglyceride levels in diabetic dyslipidaemia without any adverse drug reactions or any drug interaction. Omega-3 fatty acids were effective in reducing the triglyceride level significantly as compared to placebo. Two grams of omega-3 fatty acids were more effective than 1 gram of omega-3 fatty acids in reducing triglyceride levels.

A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

PubMed Central

Wang, Yi-lun; Li, Yu-sheng; Wei, Jie; Li, Hui; Yang, Tuo; Yang, Tu-bao; Lei, Guang-hua

2015-01-01

Objectives The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery. Methods Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software. Results Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone. Conclusion The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone. Level of Evidence Level I, meta-analysis of Level I studies. PMID:26474401

Generation of “Virtual” Control Groups for Single Arm Prostate Cancer Adjuvant Trials

PubMed Central

Koziol, James A.; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M.; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-guo; McLaren, Christine E.; Gurley, Michael J.; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W.; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. PMID:24465467

Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.

PubMed

Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

2014-01-01

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

Effects of Gait Self-Efficacy and Lower-Extremity Physical Function on Dual-Task Performance in Older Adults

PubMed Central

Banducci, Sarah E.; Daugherty, Ana M.; Fanning, Jason; Awick, Elizabeth A.; Porter, Gwenndolyn C.; Burzynska, Agnieszka; Shen, Sa; Kramer, Arthur F.; McAuley, Edward

2017-01-01

Objectives. Despite evidence of self-efficacy and physical function's influences on functional limitations in older adults, few studies have examined relationships in the context of complex, real-world tasks. The present study tested the roles of self-efficacy and physical function in predicting older adults' street-crossing performance in single- and dual-task simulations. Methods. Lower-extremity physical function, gait self-efficacy, and street-crossing success ratio were assessed in 195 older adults (60–79 years old) at baseline of a randomized exercise trial. During the street-crossing task, participants walked on a self-propelled treadmill in a virtual reality environment. Participants crossed the street without distraction (single-task trials) and conversed on a cell phone (dual-task trials). Structural equation modeling was used to test hypothesized associations independent of demographic and clinical covariates. Results. Street-crossing performance was better on single-task trials when compared with dual-task trials. Direct effects of self-efficacy and physical function on success ratio were observed in dual-task trials only. The total effect of self-efficacy was significant in both conditions. The indirect path through physical function was evident in the dual-task condition only. Conclusion. Physical function can predict older adults' performance on high fidelity simulations of complex, real-world tasks. Perceptions of function (i.e., self-efficacy) may play an even greater role. The trial is registered with United States National Institutes of Health ClinicalTrials.gov (ID: NCT01472744; Fit & Active Seniors Trial). PMID:28255557

[Non-pharmacological treatment of dementia in geriatric psychiatry care units : Scoping review].

PubMed

Göhner, Anne; Hüll, Michael; Voigt-Radloff, Sebastian

2018-02-01

The number of persons suffering from dementia will continuously increase in the coming years; therefore, evidence-based interventions are needed in geriatric psychiatric care. When evidence is poor scoping reviews may help to identify knowledge gaps and needs for research. To present an overview of clinical trials on non-pharmacological treatment for elderly with dementia in hospitals, wards and nursing homes, specializing in gerontopsychiatric care. A systematic search was carried out by one of the authors for clinical trials (randomized controlled, controlled and single group pre-post design, English and German, 1998-2014) in PsycINFO, PubMED, PSYNDEX and the Cochrane Library as well as a manual search in two relevant German peer-reviewed journals. Two authors included studies according to a priori defined inclusion criteria. One author extracted data after consulting the second author in cases of ambiguity. The risk of bias of the studies was not assessed. A total of 77 studies were identified, 29 studies on restructured treatment pathways or settings, 14 trials on environmental changes and 34 studies on therapeutic single or group interventions. Both the methodological quality of the studies and the evidence for the efficacy of non-pharmacological treatment were limited. There are clear indications for an advantage of specialized environments and treatment settings for the elderly with dementia in hospitals, wards and nursing homes. There are consistent indications for positive effects of psychosocial activation alone or in combination with cognitive or physical activation, partly with high-quality study designs. This is consistent with the German S3 guidelines for dementia. For single interventions, such as electroconvulsive therapy or horticultural activities, the level of evidence remains limited.

Corticosterone administration after a single-trial contextual fear conditioning does not influence the strength and specificity of recent and remote memory in rats.

PubMed

Bueno, Ana Paula A; de Paiva, Joselisa Péres Queiroz; Corrêa, Moisés Dos Santos; Tiba, Paula Ayako; Fornari, Raquel Vecchio

2017-03-15

It is well established that corticosterone (CORT) enhances memory consolidation of emotionally arousing experiences. Despite emotional memories being usually referred to as well remembered for long periods, there are no studies that have investigated the effects of CORT in modulating the duration and specificity of memory. In the present study, we trained Wistar rats in a single-trial contextual fear conditioning protocol and injected CORT (0.3, 1.0 or 3.0mg/kg), immediately after training, to investigate its effects on memory consolidation. Rats were tested 2 and 29days after the training session or only 29days after training to assess recent or remote memory. Our results show that animals tested for recent memory discriminated the training context from a novel one, while those tested only for remote memory generalized the fear response to both contexts. Animals tested for remote memory after being tested for recent memory were able to discriminate both contexts. These results support the literature regarding memory specificity and duration. However, CORT treatment, even at the dose of 1.0mg/kg that effectively enhanced the plasmatic hormone levels, did not affect the strength or the specificity of memory in either recent or remote memory tests. We hypothesize that the lack of effect of CORT treatment could be due to the low arousing training experience of the single-trial protocol which, despite being sufficient to induce significant recent and remote memory consolidation, may not be sufficient to allow the memory-enhancing effect of CORT. Copyright © 2017 Elsevier Inc. All rights reserved.

Micronutrient supplementation in adults with HIV infection.

PubMed

Visser, Marianne E; Durao, Solange; Sinclair, David; Irlam, James H; Siegfried, Nandi

2017-05-18

Micronutrient deficiencies are common among adults living with HIV disease, particularly in low-income settings where the diet may be low in essential vitamins and minerals. Some micronutrients play critical roles in maintenance of the immune system, and routine supplementation could therefore be beneficial. This is an update of a Cochrane Review previously published in 2010. To assess whether micronutrient supplements are effective and safe in reducing mortality and HIV-related morbidity of HIV-positive adults (excluding pregnant women). We performed literature searches from January 2010 to 18 November 2016 for new randomized controlled trials (RCTs) of micronutrient supplements since the previous review included all trials identified from searches prior to 2010. We searched the CENTRAL (the Cochrane Library), Embase, and PubMed databases. Also we checked the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov trials registers. We also checked the reference lists of all new included trials. We included RCTs that compared supplements that contained either single, dual, or multiple micronutrients with placebo, no treatment, or other supplements. We excluded studies that were primarily designed to investigate the role of micronutrients for the treatment of HIV-positive participants with metabolic morbidity related to highly active antiretroviral therapy (HAART). Primary outcomes included all-cause mortality, morbidity, and disease progression. Two review authors independently selected trials for inclusion, and appraised trial quality for risk of bias. Where possible, we presented results as risk ratios (RR) for dichotomous variables, as hazard ratios (HRs) for time-to-event data, and as mean differences (MD) for continuous variables, each with 95% confidence intervals (CIs). Since we were often unable to pool the outcome data, we tabulated it for each comparison. We assessed the certainty of the evidence using the GRADE approach. We included 33 trials with 10,325 participants, of which 17 trials were new trials. Ten trials compared a daily multiple micronutrient supplement to placebo in doses up to 20 times the dietary reference intake, and one trial compared a daily standard dose with a high daily dose of multivitamins. Nineteen trials compared supplementation with single or dual micronutrients (such as vitamins A and D, zinc, and selenium) to placebo, and three trials compared different dosages or combinations of micronutrients. Multiple micronutrientsWe conducted analyses across antiretroviral therapy (ART)-naive adults (3 trials, 1448 participants), adults on antiretroviral therapy (ART) (1 trial, 400 participants), and ART-naive adults with concurrent active tuberculosis (3 trials, 1429 participants). Routine multiple micronutrient supplementation may have little or no effect on mortality in adults living with HIV (RR 0.91, 95% CI 0.72 to 1.15; 7 trials, 2897 participants, low certainty evidence).Routine supplementation for up to two years may have little or no effect on the average of mean CD4+ cell count (MD 26.40 cells/mm³, 95% CI -22.91 to 75.70; 6 trials, 1581 participants, low certainty evidence), or the average of mean viral load (MD -0.1 log 10 viral copies, 95% CI -0.26 to 0.06; 4 trials, 840 participants, moderate certainty evidence). One additional trial in ART-naïve adults did report an increase in the time to reach a CD4+ cell count < 250 cells/mm³ after two years of high dose supplementation in Botswana (HR 0.48, 95% CI 0.26 to 0.88; 1 trial, 439 participants). However, the trial authors reported this effect only in the trial arm that received multiple micronutrients plus selenium (not either supplementation alone), which is inconsistent with the findings of other trials that used similar combinations of micronutrients and selenium.In one additional trial that compared high-dose multiple micronutrient supplementation with standard doses in people on ART, peripheral neuropathy was lower with high dose supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI 0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to increased adverse events (elevated alanine transaminase (ALT) levels) in the high dose group. Single or dual micronutrientsNone of the trials of single or dual micronutrient supplements were adequately powered to assess for effects on mortality or morbidity outcomes. No clinically significant changes in CD4 cell count (data not pooled, 14 trials, 2370 participants, very low or low certainty evidence) or viral load (data not pooled, seven studies, 1334 participants, very low or low certainty evidence), were reported. Supplementation probably does increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D: 4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty evidence) and may also increase blood concentrations of vitamin A (data not pooled, 3 trials, 495 participants, low certainty evidence), especially in those who are deficient. The analyses of the available trials have not revealed consistent clinically important benefits with routine multiple micronutrient supplementation in people living with HIV. Larger trials might reveal small but important effects.These findings should not be interpreted as a reason to deny micronutrient supplements for people living with HIV where specific deficiencies are found or where the person's diet is insufficient to meet the recommended daily allowance of vitamins and minerals.

Analysis of force profile during a maximum voluntary isometric contraction task.

PubMed

Househam, Elizabeth; McAuley, John; Charles, Thompson; Lightfoot, Timothy; Swash, Michael

2004-03-01

This study analyses maximum voluntary isometric contraction (MVIC) and its measurement by recording the force profile during maximal-effort, 7-s hand-grip contractions. Six healthy subjects each performed three trials repeated at short intervals to study variation from fatigue. These three trials were performed during three separate sessions at daily intervals to look at random variation. A pattern of force development during a trial was identified. An initiation phase, with or without an initiation peak, was followed by a maintenance phase, sometimes with secondary pulses and an underlying decline in force. Of these three MVIC parameters, maximum force during the maintenance phase showed less random variability compared to intertrial fatigue variability than did maximum force during the initiation phase or absolute maximum force. Analysis of MVIC as a task, rather than a single, maximal value reveals deeper levels of motor control in its generation. Thus, force parameters other than the absolute maximum force may be better suited to quantification of muscle performance in health and disease.

Phase I/II adaptive design for drug combination oncology trials

PubMed Central

Wages, Nolan A.; Conaway, Mark R.

2014-01-01

Existing statistical methodology on dose finding for combination chemotherapies has focused on toxicity considerations alone in finding a maximum tolerated dose combination to recommend for further testing of efficacy in a phase II setting. Recently, there has been increasing interest in integrating phase I and phase II trials in order to facilitate drug development. In this article, we propose a new adaptive phase I/II method for dual-agent combinations that takes into account both toxicity and efficacy after each cohort inclusion. The primary objective, both within and at the conclusion of the trial, becomes finding a single dose combination with an acceptable level of toxicity that maximizes efficacious response. We assume that there exist monotone dose–toxicity and dose–efficacy relationships among doses of one agent when the dose of other agent is fixed. We perform extensive simulation studies that demonstrate the operating characteristics of our proposed approach, and we compare simulated results to existing methodology in phase I/II design for combinations of agents. PMID:24470329

A methodology for assessing the effect of correlations among muscle synergy activations on task-discriminating information.

PubMed

Delis, Ioannis; Berret, Bastien; Pozzo, Thierry; Panzeri, Stefano

2013-01-01

Muscle synergies have been hypothesized to be the building blocks used by the central nervous system to generate movement. According to this hypothesis, the accomplishment of various motor tasks relies on the ability of the motor system to recruit a small set of synergies on a single-trial basis and combine them in a task-dependent manner. It is conceivable that this requires a fine tuning of the trial-to-trial relationships between the synergy activations. Here we develop an analytical methodology to address the nature and functional role of trial-to-trial correlations between synergy activations, which is designed to help to better understand how these correlations may contribute to generating appropriate motor behavior. The algorithm we propose first divides correlations between muscle synergies into types (noise correlations, quantifying the trial-to-trial covariations of synergy activations at fixed task, and signal correlations, quantifying the similarity of task tuning of the trial-averaged activation coefficients of different synergies), and then uses single-trial methods (task-decoding and information theory) to quantify their overall effect on the task-discriminating information carried by muscle synergy activations. We apply the method to both synchronous and time-varying synergies and exemplify it on electromyographic data recorded during performance of reaching movements in different directions. Our method reveals the robust presence of information-enhancing patterns of signal and noise correlations among pairs of synchronous synergies, and shows that they enhance by 9-15% (depending on the set of tasks) the task-discriminating information provided by the synergy decompositions. We suggest that the proposed methodology could be useful for assessing whether single-trial activations of one synergy depend on activations of other synergies and quantifying the effect of such dependences on the task-to-task differences in muscle activation patterns.

Single dental implant retained mandibular complete dentures – influence of the loading protocol: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Over the years, there has been a strong consensus in dentistry that at least two implants are required to retain a complete mandibular denture. It has been shown in several clinical trials that one single median implant can retain a mandibular overdenture sufficiently well for up to 5 years without implant failures, when delayed loading was used. However, other trials have reported conflicting results with in part considerable failure rates when immediate loading was applied. Therefore it is the purpose of the current randomized clinical trial to test the hypothesis that immediate loading of a single mandibular midline implant with an overdenture will result in a comparable clinical outcome as using the standard protocol of delayed loading. Methods/design This prospective nine-center randomized controlled clinical trial is still ongoing. The final patient will complete the trial in 2016. In total, 180 edentulous patients between 60 and 89 years with sufficient complete dentures will receive one median implant in the edentulous mandible, which will retain the existing complete denture using a ball attachment. Loading of the median implant is either immediately after implant placement (experimental group) or delayed by 3 months of submerged healing at second-stage surgery (control group). Follow-up of patients will be performed for 24 months after implant loading. The primary outcome measure is non-inferiority of implant success rate of the experimental group compared to the control group. The secondary outcome measures encompass clinical, technical and subjective variables. The study was funded by the Deutsche Forschungsgemeinschaft (German research foundation, KE 477/8-1). Discussion This multi-center clinical trial will give information on the ability of a single median implant to retain a complete mandibular denture when immediately loaded. If viable, this treatment option will strongly improve everyday dental practice. Trial registration The trial has been registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00003730 since 23 August 2012. (http://www.germanctr.de). PMID:24884848

Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator, following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy

PubMed Central

Ricotti, Valeria; Spinty, Stefan; Roper, Helen; Hughes, Imelda; Tejura, Bina; Robinson, Neil; Layton, Gary; Davies, Kay

2016-01-01

Purpose SMT C1100 is a utrophin modulator being evaluated as a treatment for Duchenne muscular dystrophy (DMD). This study, the first in pediatric DMD patients, reports the safety, tolerability and PK parameters of single and multiple doses of SMT C1100, as well as analyze potential biomarkers of muscle damage. Methods This multicenter, Phase 1 study enrolled 12 patients, divided equally into three groups (A–C). Group A were given 50 mg/kg on Days 1 and 11, and 50 mg/kg bid on Days 2 to 10. Group B and C received 100 mg/kg on Days 1 and 11; Group B and Group C were given 100 mg/kg bid and 100 mg/kg tid, respectively, on Days 2 to 10. A safety review was performed on all patients following the single dose and there was at least 2 weeks between each dose escalation, for safety and PK review. Adverse events (AEs) were monitored throughout the study. Results Most patients experienced mild AEs and there were no serious AEs. Two patients required analgesia for pain (headache, ear pain and toothache). One patient experienced moderate psychiatric AEs (abnormal behaviour and mood swings). Plasma concentrations of SMT C1100 at Days 1 and 11 indicated a high degree of patient variability regardless of dose. Unexpectedly the SMT C1100 levels were significantly lower than similar doses administered to healthy volunteers in an earlier clinical study. In general, individual baseline changes of creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase levels fell with SMT C1100 dosing. Conclusions SMT C1100 was well tolerated in pediatric DMD patients. Trial Registration ClinicalTrials.gov NCT02383511 PMID:27055247

Relationship Between Circulating Fatty Acids and Fatty Acid Ethanolamide Levels After a Single 2-h Dietary Fat Feeding in Male Sprague-Dawley Rats : Elevated levels of oleoylethanolamide, palmitoylethanolamide, linoleoylethanolamide, arachidonoylethanolamide and docosahexanoylethanolamide after a single 2 h dietary fat feeding in male Sprague Dawley rats.

PubMed

Olatinsu, Anthonia O; Sihag, Jyoti; Jones, Peter J H

2017-11-01

Previous studies show that long term variations in dietary fat consumption impact circulating fatty acid ethanolamide (FAE) concentrations, however, few studies have investigated short term effects of dietary fat feeding on FAE levels. The trial's objective was to explore the effect of acute feeding of varying amounts of dietary n-9 and n-3 fatty acids on plasma and organ levels of FAE. Sixty-four rats were assigned to four groups fed meals containing 40% of energy as either safflower oil (control), canola oil (CO), or DHA rich oil (DRO), each consumed as a bolus within a 2-h window. Plasma and tissue FAE levels were measured at 3, 6, 12 and 24 h following the bolus. FAE profiles over time exhibited patterns that were specific both to FAE and to dietary fat type provided. At 3 h, plasma and liver OEA levels were higher (p < 0.05) in the 95% CO:5% DRO compared with other groups. At 12 h, plasma PEA levels were lower (p < 0.05) in the 50% CO:50% DRO group compared to the 95% CO group. Plasma DEA levels showed an increase (p < 0.05) only after 24 h of feeding. All four dietary groups manifested increased DEA levels in a dose-dependent manner. Data demonstrate that a single meal feeding of diets with different ratios of fat types impacts tissue levels of FAE within a short time frame, which could further influence the physiological roles of FAE on appetite regulation and energy expenditure.

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

PubMed

2007-02-19

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

Losing Control in Social Situations: How the Presence of Others Affects Neural Processes Related to Sense of Agency

PubMed Central

Fleming, Stephen

2018-01-01

Social contexts substantially influence individual behavior, but little is known about how they affect cognitive processes related to voluntary action. Previously, it has been shown that social context reduces participants’ sense of agency over the outcomes of their actions and outcome monitoring. In this fMRI study on human volunteers, we investigated the neural mechanisms by which social context alters sense of agency. Participants made costly actions to stop inflating a balloon before it burst. On “social” trials, another player could act in their stead, but we analyzed only trials in which the other player remained passive. We hypothesized that mentalizing processes during social trials would affect decision-making fluency and lead to a decreased sense of agency. In line with this hypothesis, we found increased activity in the bilateral temporo-parietal junction (TPJ), precuneus, and middle frontal gyrus during social trials compared with nonsocial trials. Activity in the precuneus was, in turn, negatively related to sense of agency at a single-trial level. We further found a double dissociation between TPJ and angular gyrus (AG): activity in the left AG was not sensitive to social context but was negatively related to sense of agency. In contrast, activity in the TPJ was modulated by social context but was not sensitive to sense of agency. PMID:29527568

Losing Control in Social Situations: How the Presence of Others Affects Neural Processes Related to Sense of Agency.

PubMed

Beyer, Frederike; Sidarus, Nura; Fleming, Stephen; Haggard, Patrick

2018-01-01

Social contexts substantially influence individual behavior, but little is known about how they affect cognitive processes related to voluntary action. Previously, it has been shown that social context reduces participants' sense of agency over the outcomes of their actions and outcome monitoring. In this fMRI study on human volunteers, we investigated the neural mechanisms by which social context alters sense of agency. Participants made costly actions to stop inflating a balloon before it burst. On "social" trials, another player could act in their stead, but we analyzed only trials in which the other player remained passive. We hypothesized that mentalizing processes during social trials would affect decision-making fluency and lead to a decreased sense of agency. In line with this hypothesis, we found increased activity in the bilateral temporo-parietal junction (TPJ), precuneus, and middle frontal gyrus during social trials compared with nonsocial trials. Activity in the precuneus was, in turn, negatively related to sense of agency at a single-trial level. We further found a double dissociation between TPJ and angular gyrus (AG): activity in the left AG was not sensitive to social context but was negatively related to sense of agency. In contrast, activity in the TPJ was modulated by social context but was not sensitive to sense of agency.

RECCAS - REmoval of Cytokines during CArdiac Surgery: study protocol for a randomised controlled trial.

PubMed

Baumann, Andreas; Buchwald, Dirk; Annecke, Thorsten; Hellmich, Martin; Zahn, Peter K; Hohn, Andreas

2016-03-12

On-pump cardiac surgery triggers a significant postoperative systemic inflammatory response, sometimes resulting in multiple-organ dysfunction associated with poor clinical outcome. Extracorporeal cytokine elimination with a novel haemoadsorption (HA) device (CytoSorb®) promises to attenuate inflammatory response. This study primarily assesses the efficacy of intraoperative HA during cardiopulmonary bypass (CPB) to reduce the proinflammatory cytokine burden during and after on-pump cardiac surgery, and secondarily, we aim to evaluate effects on postoperative organ dysfunction and outcomes in patients at high risk. This will be a single-centre randomised, two-arm, patient-blinded trial of intraoperative HA in patients undergoing on-pump cardiac surgery. Subjects will be allocated to receive either CPB with intraoperative HA or standard CPB without HA. The primary outcome is the difference in mean interleukin 6 (IL-6) serum levels between the two study groups on admission to the intensive care unit. A total number of 40 subjects was calculated as necessary to detect a clinically relevant 30 % reduction in postoperative IL-6 levels. Secondary objectives evaluate effects of HA on markers of inflammation up to 48 hours postoperatively, damage to the endothelial glycocalyx and effects on clinical scores and parameters of postoperative organ dysfunction and outcomes. In this pilot trial we try to assess whether intraoperative HA with CytoSorb® can relevantly reduce postoperative IL-6 levels in patients undergoing on-pump cardiac surgery. Differences in secondary outcome variables between the study groups may give rise to further studies and may lead to a better understanding of the mechanisms of haemoadsorption. German Clinical Trials Register number DRKS00007928 (Date of registration 3 Aug 2015).

Effects of Oral L-Carnitine Administration in Narcolepsy Patients: A Randomized, Double-Blind, Cross-Over and Placebo-Controlled Trial

PubMed Central

Miyagawa, Taku; Kawamura, Hiromi; Obuchi, Mariko; Ikesaki, Asuka; Ozaki, Akiko; Tokunaga, Katsushi; Inoue, Yuichi; Honda, Makoto

2013-01-01

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities. A genome-wide association study (GWAS) identified a novel narcolepsy-related single nucleotide polymorphism (SNP), which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral l-carnitine for the treatment of narcolepsy, we performed a clinical trial administering l-carnitine (510 mg/day) to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02). l-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. l-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo. This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. Trial Registration University hospital Medical Information Network (UMIN) UMIN000003760 PMID:23349733

Serum levels of bupivacaine after pre-peritoneal bolus vs. epidural bolus injection for analgesia in abdominal surgery: A safety study within a randomized controlled trial

PubMed Central

Geerts, Bart F.; van Dieren, Susan; Besselink, Marc G.; Veelo, Denise P.; Lirk, Philipp

2017-01-01

Background Continuous wound infiltration (CWI) has become increasingly popular in recent years as an alternative to epidural analgesia. As catheters are not placed until the end of surgery, more intraoperative opioid analgesics might be needed. We, therefore, added a single pre-peritoneal bolus of bupivacaine at the start of laparotomy, similar to the bolus given with epidural analgesia. Methods This was a comparative study within a randomized controlled trial (NTR4948). Patients undergoing hepato-pancreato-biliary surgery received either a pre-peritoneal bolus of 30ml bupivacaine 0.25%, or an epidural bolus of 10ml bupivacaine 0.25% at the start of laparotomy. In a subgroup of patients, we sampled blood and determined bupivacaine serum levels 20, 40, 60 and 80 minutes after bolus injection. We assumed toxicity of bupivacaine to be >1000 ng/ml. Results A total of 20 patients participated in this sub-study. All plasma levels measured as well as the upper limit of the predicted 99% confidence intervals per time point were well below the toxicity limit. In a mixed linear-effect model both groups did not differ statistically significant (p = 0.131). The intra-operative use of opioids was higher with CWI as compared to epidural (86 (SD 73) μg sufentanil vs. 50 (SD 32). Conclusions In this exploratory study, the pre-peritoneal bolus using bupivacaine resulted in serum bupivacaine concentrations well below the commonly accepted toxic threshold. With CWI more additional analgesics are needed intraoperatively as compared to epidural analgesia, although this is compensated by a reduction in use of vasopressors with CWI. Trial registration Netherlands Trial Register NTR4948 PMID:28614364

Effects of endovascular cooling on infarct size in ST-segment elevation myocardial infarction: A patient-level pooled analysis from randomized trials.

PubMed

Dae, Michael; O'Neill, William; Grines, Cindy; Dixon, Simon; Erlinge, David; Noc, Marko; Holzer, Michael; Dee, Anne

2018-06-01

This study sought to examine the relationship between temperature at reperfusion and infarct size. Hypothermia consistently reduces infarct size when administered prior to reperfusion in animal studies, however, clinical results have been inconsistent. We performed a patient-level pooled analysis from six randomized control trials of endovascular cooling during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) in 629 patients in which infarct size was assessed within 1 month after randomization by either single-photon emission computed tomography (SPECT) or cardiac magnetic resonance imaging (cMR). In anterior infarct patients, after controlling for variability between studies, mean infarct size in controls was 21.3 (95%CI 17.4-25.3) and in patients with hypothermia <35°C it was 14.8 (95%CI 10.1-19.6), which was a statistically significant absolute reduction of 6.5%, or a 30% relative reduction in infarct size (P = 0.03). There was no significant difference in infarct size in anterior ≥35°C, or inferior infarct patients. There was no difference in the incidence of death, ventricular arrhythmias, or re-infarction due to stent thrombosis between hypothermia and control patients. The present study, drawn from a patient-level pooled analysis of six randomized trials of endovascular cooling during primary PCI in STEMI, showed a significant reduction in infarct size in patients with anterior STEMI who were cooled to <35°C at the time of reperfusion. The results support the need for trials in patients with anterior STEMI using more powerful cooling devices to optimize the delivery of hypothermia prior to reperfusion. © 2017 The Authors. Journal of Interventional Cardiology Published by Wiley Periodicals, Inc.

The PREEMPT study - evaluating smartphone-assisted n-of-1 trials in patients with chronic pain: study protocol for a randomized controlled trial.

PubMed

Barr, Colin; Marois, Maria; Sim, Ida; Schmid, Christopher H; Wilsey, Barth; Ward, Deborah; Duan, Naihua; Hays, Ron D; Selsky, Joshua; Servadio, Joseph; Schwartz, Marc; Dsouza, Clyde; Dhammi, Navjot; Holt, Zachary; Baquero, Victor; MacDonald, Scott; Jerant, Anthony; Sprinkle, Ron; Kravitz, Richard L

2015-02-27

Chronic pain is prevalent, costly, and clinically vexatious. Clinicians typically use a trial-and-error approach to treatment selection. Repeated crossover trials in a single patient (n-of-1 trials) may provide greater therapeutic precision. N-of-1 trials are the most direct way to estimate individual treatment effects and are useful in comparing the effectiveness and toxicity of different analgesic regimens. The goal of the PREEMPT study is to test the 'Trialist' mobile health smartphone app, which has been developed to make n-of-1 trials easier to accomplish, and to provide patients and clinicians with tools for individualizing treatments for chronic pain. A randomized controlled trial is being conducted to test the feasibility and effectiveness of the Trialist app. A total of 244 participants will be randomized to either the Trialist app intervention group (122 patients) or a usual care control group (122 patients). Patients assigned to the Trialist app will work with their clinicians to set up an n-of-1 trial comparing two pain regimens, selected from a menu of flexible options. The Trialist app provides treatment reminders and collects data entered daily by the patient on pain levels and treatment side effects. Upon completion of the n-of-1 trial, patients review results with their clinicians and develop a long-term treatment plan. The primary study outcome (comparing Trialist to usual care patients) is pain-related interference with daily functioning at 26 weeks. Trialist will allow patients and clinicians to conduct personalized n-of-1 trials. In prior studies, n-of-1 trials have been shown to encourage greater patient involvement with care, which has in turn been associated with better health outcomes. mHealth technology implemented using smartphones may offer an efficient means of facilitating n-of-1 trials so that more patients can benefit from this approach. ClinicalTrials.gov: NCT02116621 , first registered 15 April 2014.

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

PubMed Central

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

2016-01-01

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

Method for enhancing single-trial P300 detection by introducing the complexity degree of image information in rapid serial visual presentation tasks

PubMed Central

Lin, Zhimin; Zeng, Ying; Tong, Li; Zhang, Hangming; Zhang, Chi

2017-01-01

The application of electroencephalogram (EEG) generated by human viewing images is a new thrust in image retrieval technology. A P300 component in the EEG is induced when the subjects see their point of interest in a target image under the rapid serial visual presentation (RSVP) experimental paradigm. We detected the single-trial P300 component to determine whether a subject was interested in an image. In practice, the latency and amplitude of the P300 component may vary in relation to different experimental parameters, such as target probability and stimulus semantics. Thus, we proposed a novel method, Target Recognition using Image Complexity Priori (TRICP) algorithm, in which the image information is introduced in the calculation of the interest score in the RSVP paradigm. The method combines information from the image and EEG to enhance the accuracy of single-trial P300 detection on the basis of traditional single-trial P300 detection algorithm. We defined an image complexity parameter based on the features of the different layers of a convolution neural network (CNN). We used the TRICP algorithm to compute for the complexity of an image to quantify the effect of different complexity images on the P300 components and training specialty classifier according to the image complexity. We compared TRICP with the HDCA algorithm. Results show that TRICP is significantly higher than the HDCA algorithm (Wilcoxon Sign Rank Test, p<0.05). Thus, the proposed method can be used in other and visual task-related single-trial event-related potential detection. PMID:29283998

Mixed response and time-to-event endpoints for multistage single-arm phase II design.

PubMed

Lai, Xin; Zee, Benny Chung-Ying

2015-06-04

The objective of phase II cancer clinical trials is to determine if a treatment has sufficient activity to warrant further study. The efficiency of a conventional phase II trial design has been the object of considerable debate, particularly when the study regimen is characteristically cytostatic. At the time of development of a phase II cancer trial, we accumulated clinical experience regarding the time to progression (TTP) for similar classes of drugs and for standard therapy. By considering the time to event (TTE) in addition to the tumor response endpoint, a mixed-endpoint phase II design may increase the efficiency and ability of selecting promising cytotoxic and cytostatic agents for further development. We proposed a single-arm phase II trial design by extending the Zee multinomial method to fully use mixed endpoints with tumor response and the TTE. In this design, the dependence between the probability of response and the TTE outcome is modeled through a Gaussian copula. Given the type I and type II errors and the hypothesis as defined by the response rate (RR) and median TTE, such as median TTP, the decision rules for a two-stage phase II trial design can be generated. We demonstrated through simulation that the proposed design has a smaller expected sample size and higher early stopping probability under the null hypothesis than designs based on a single-response endpoint or a single TTE endpoint. The proposed design is more efficient for screening new cytotoxic or cytostatic agents and less likely to miss an effective agent than the alternative single-arm design.

Vaxchora: A Single-Dose Oral Cholera Vaccine.

PubMed

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

2017-07-01

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

Current status of evidence-based sports medicine.

PubMed

Harris, Joshua D; Cvetanovich, Gregory; Erickson, Brandon J; Abrams, Geoffrey D; Chahal, Jaskarndip; Gupta, Anil K; McCormick, Frank M; Bach, Bernard R

2014-03-01

The purpose of this investigation is to determine the proportion of sports medicine studies that are labeled as Level I Evidence in 5 journals and compare the quality of surgical and nonsurgical studies using simple quality assessment tools (Consolidated Standards of Reporting Trials [CONSORT] and Jadad). By use of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines over the prior 2 years in the top 5 (citation and impact factor based) sports medicine journals, only Level I Evidence studies were eligible for inclusion and were analyzed. All study types (therapeutic, prognostic, diagnostic, and economic) were analyzed. Study quality was assessed with the level of evidence, Jadad score, and CONSORT 2010 guidelines. Study demographic data were compared among journals and between surgical and nonsurgical studies by use of χ(2), 1-way analysis of variance, and 2-sample Z tests. We analyzed 190 Level I Evidence studies (10% of eligible studies) (119 randomized controlled trials [RCTs]). Therapeutic, nonsurgical, single-center studies from the United States were the most common studies published. Sixty-two percent of studies reported a financial conflict of interest. The knee was the most common body part studied, and track-and-field/endurance sports were the most common sports analyzed. Significant differences (P < .05) were shown in Jadad and CONSORT scores among the journals reviewed. Overall, the Jadad and CONSORT scores were 2.71 and 77%, respectively. No differences (P > .05) were shown among journals based on the proportion of Level I studies or appropriate randomization. Significant strengths and limitations of RCTs were identified. This study showed that Level I Evidence and RCTs comprise 10% and 6% of contemporary sports medicine literature, respectively. Therapeutic, nonsurgical, single-center studies are the most common publications with Level I Evidence. Significant differences across sports medicine journals were found in study quality. Surgical studies appropriately described randomization, blinding, and patient enrollment significantly more than nonsurgical studies. Level I, systematic review of Level I studies. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

The Malaysian Childhood Obesity Treatment Trial (MASCOT).

PubMed

Sharifah, W W; Nur, Hana H; Ruzita, A T; Roslee, R; Reilly, J J

2011-08-01

The present study describes a randomised controlled trial (RCT) based on a novel, generalisable intervention for childhood obesity, comparing the intervention with a no-treatment control group. The Malaysian Childhood Obesity Treatment Trial (MASCOT) was a single-blind RCT of a dietetic treatment for childhood obesity in children of primary school age (7 to 11 years old) in Kuala Lumpur, Malaysia. The MASCOT comprising eight sessions, of an 8-hour family-centred group treatment programme is described, based on behavioural change techniques. The study sample was characterised by BMI z-score, health related quality of life reported by participants and their parents (PedsQL questionnaire), objectively measured habitual physical activity and sedentary behaviour (Actigraph accelerometry) The MASCOT sample of 107 children was characterised by a low quality of life, mean total score on PedsQL 67.7 (4.5) as reported by the children, and 66.0 (16.4) as reported by their parents. The children spent, on average, 89% of their waking day on sedentary activity, and 1% of the day in moderate-vigorous intensity physical activity, equivalent to only around 8 minutes/day. Obese children in the MASCOT study had an impaired quality of life, high levels of sedentary behaviour and very low levels of physical activity.

Effects of Testosterone Therapy on Muscle Performance and Physical Function in Older Men with Mobility Limitations (The TOM Trial): Design and Methods

PubMed Central

LeBrasseur, Nathan K.; Lajevardi, Newsha; Miciek, Renee; Mazer, Norman; Storer, Thomas W.; Bhasin, Shalender

2010-01-01

The TOM study is the first, single-site, placebo-controlled, randomized clinical trial designed to comprehensively determine the effects of testosterone administration on muscle strength and physical function in older men with mobility limitations. A total of 252 community dwelling individuals aged 65 and older with low testosterone levels and self-reported limitations in mobility and short physical performance battery (SPPB) score between 4 and 9 will be randomized to receive either placebo or testosterone therapy for 6 months. The primary objective is to determine whether testosterone therapy improves maximal voluntary muscle strength as quantified by the one repetition maximum. Secondary outcomes will include measures of physical function (walking, stair climbing and a lifting and lowering task), habitual physical activity and self-reported disability. The effects of testosterone on affect, fatigue and sense of well being will also be assessed. Unique aspects of the TOM Trial include selection of men with self-reported as well as objectively demonstrable functional limitations, community-based screening and recruitment, adjustment of testosterone dose to ensure serum testosterone levels in the target range while maintaining blinding, and inclusion of a range of self-reported and performance-based physical function measures as outcomes. Clinicaltrials.gov identifier: NCT00240981. PMID:18996225

Effects of testosterone therapy on muscle performance and physical function in older men with mobility limitations (The TOM Trial): design and methods.

PubMed

LeBrasseur, Nathan K; Lajevardi, Newsha; Miciek, Renee; Mazer, Norman; Storer, Thomas W; Bhasin, Shalender

2009-03-01

The TOM study is the first, single-site, placebo-controlled, randomized clinical trial designed to comprehensively determine the effects of testosterone administration on muscle strength and physical function in older men with mobility limitations. A total of 252 community dwelling individuals aged 65 and older with low testosterone levels and self-reported limitations in mobility and short physical performance battery (SPPB) scores between 4 and 9 will be randomized to receive either placebo or testosterone therapy for 6 months. The primary objective is to determine whether testosterone therapy improves maximal voluntary muscle strength as quantified by the one repetition maximum. Secondary outcomes will include measures of physical function (walking, stair climbing and a lifting and lowering task), habitual physical activity and self-reported disability. The effects of testosterone on affect, fatigue and sense of well being will also be assessed. Unique aspects of the TOM Trial include selection of men with self-reported as well as objectively demonstrable functional limitations, community-based screening and recruitment, adjustment of testosterone dose to ensure serum testosterone levels in the target range while maintaining blinding, and inclusion of a range of self-reported and performance-based physical function measures as outcomes. Clinicaltrials.gov identifier: NCT00240981.

A P300-based Brain-Computer Interface with Stimuli on Moving Objects: Four-Session Single-Trial and Triple-Trial Tests with a Game-Like Task Design

PubMed Central

Ganin, Ilya P.; Shishkin, Sergei L.; Kaplan, Alexander Y.

2013-01-01

Brain-computer interfaces (BCIs) are tools for controlling computers and other devices without using muscular activity, employing user-controlled variations in signals recorded from the user’s brain. One of the most efficient noninvasive BCIs is based on the P300 wave of the brain’s response to stimuli and is therefore referred to as the P300 BCI. Many modifications of this BCI have been proposed to further improve the BCI’s characteristics or to better adapt the BCI to various applications. However, in the original P300 BCI and in all of its modifications, the spatial positions of stimuli were fixed relative to each other, which can impose constraints on designing applications controlled by this BCI. We designed and tested a P300 BCI with stimuli presented on objects that were freely moving on a screen at a speed of 5.4°/s. Healthy participants practiced a game-like task with this BCI in either single-trial or triple-trial mode within four sessions. At each step, the participants were required to select one of nine moving objects. The mean online accuracy of BCI-based selection was 81% in the triple-trial mode and 65% in the single-trial mode. A relatively high P300 amplitude was observed in response to targets in most participants. Self-rated interest in the task was high and stable over the four sessions (the medians in the 1st/4th sessions were 79/84% and 76/71% in the groups practicing in the single-trial and triple-trial modes, respectively). We conclude that the movement of stimulus positions relative to each other may not prevent the efficient use of the P300 BCI by people controlling their gaze, e.g., in robotic devices and in video games. PMID:24302977

Involving South Asian patients in clinical trials.

PubMed

Hussain-Gambles, M; Leese, B; Atkin, K; Brown, J; Mason, S; Tovey, P

2004-10-01

To investigate how South Asian patients conceptualise the notion of clinical trials and to identify key processes that impact on trial participation and the extent to which communication difficulties, perceptions of risk and attitudes to authority influence these decisions. Also to identify whether 'South Asian' patients are homogeneous in these issues, and which factors differ between different South Asian subgroups and finally how professionals regard the involvement of South Asian patients and their views on strategies to increase participation. A review of the literature on minority ethnic participation in clinical trials was followed by three qualitative interview studies. Interviews were taped and transcribed (and translated if required) and subjected to framework analysis. Face-to-face interviews were conducted with 25 health professionals; 60 South Asian lay people who had not taken part in a trial and 15 South Asian trial participants. Motivations for trial participation were identified as follows: to help society, to improve own health or that of family and friends, out of obligation to the doctor and to increase scientific knowledge. Deterrents were concerns about drug side-effects, busy lifestyles, language, previous bad experiences, mistrust and feelings of not belonging to British society. There was no evidence of antipathy amongst South Asians to the concept of clinical trials and, overall, the younger respondents were more knowledgeable than the older ones. Problems are more likely to be associated with service delivery. Lack of being approached was a common response. Lay-reported factors that might affect South Asian participation in clinical trials include age, language, social class, feeling of not belonging/mistrust, culture and religion. Awareness of clinical trials varied between each group. There are more similarities than differences in attitudes towards clinical trial participation between the South Asian and the general population. Important decisions, such as participation in clinical trials, are likely to be made by those family members who are fluent in English and younger. Social class appears to be more important than ethnicity, and older South Asian people and those from working class backgrounds appear to be more mistrustful. Approachable patients (of the same gender, social class and fluent in English) tend to be 'cherry picked' to clinical trials. This practice was justified because of a lack of time and resources and inadequate support. South Asian patients might be systematically excluded from trials owing to the increased cost and time associated with their inclusion, particularly in relation to the language barrier. Under-representation might also be due to passive exclusion associated with cultural stereotypes. Other characteristics such as gender, age, educational level and social class can also affect trial inclusion. Effective strategies for South Asian recruitment to clinical trials include: using multi-recruitment strategies; defining the demographic and social profiles of the population to be included; using focus groups to identify any potential barriers; consulting representative community members to provide assistance in the study; ensuring eligibility criteria are set as wide as possible; developing educational and recruitment approaches to attract ethnic minority health professionals; ensuring health professionals are adequately trained in culturally and ethnically orientated service provision; determining the most effective mass media to use in study promotion and recruitment; and targeting inner-city, single-handed practices likely to have high ethnic minority populations. Future research should consider: responses when invited to participate; the role of methodological and organisational barriers to recruitment; the complexities of recruitment from a health professional perspective; developing culturally sensitive research methods; the magnitude of the problem of under-recruitment; strategies to encourage inner-city, single-handed GP participation; and other factors affecting trial inclusion, such as age, gender, educational level and socio-cultural background.

Analgesic effects in dogs of carprofen and pethidine together compared with the effects of either drug alone.

PubMed

Slingsby, L S; Waterman-Pearson, A E

2001-04-07

Thirty bitches undergoing routine neutering were used in an assessor-blinded trial of the postoperative analgesic effects of pethidine and carprofen administered either together or singly. The level of analgesia was assessed by visual analogue scale (VAS) scores for pain and sedation and by nociceptive mechanical threshold testing. The two drugs administered together, and carprofen alone, provided good postoperative analgesia as assessed by VAS scoring. Pethidine alone did not provide postoperative analgesia of sufficient duration.

Blockchain technology for improving clinical research quality.

PubMed

Benchoufi, Mehdi; Ravaud, Philippe

2017-07-19

Reproducibility, data sharing, personal data privacy concerns and patient enrolment in clinical trials are huge medical challenges for contemporary clinical research. A new technology, Blockchain, may be a key to addressing these challenges and should draw the attention of the whole clinical research community.Blockchain brings the Internet to its definitive decentralisation goal. The core principle of Blockchain is that any service relying on trusted third parties can be built in a transparent, decentralised, secure "trustless" manner at the top of the Blockchain (in fact, there is trust, but it is hardcoded in the Blockchain protocol via a complex cryptographic algorithm). Therefore, users have a high degree of control over and autonomy and trust of the data and its integrity. Blockchain allows for reaching a substantial level of historicity and inviolability of data for the whole document flow in a clinical trial. Hence, it ensures traceability, prevents a posteriori reconstruction and allows for securely automating the clinical trial through what are called Smart Contracts. At the same time, the technology ensures fine-grained control of the data, its security and its shareable parameters, for a single patient or group of patients or clinical trial stakeholders.In this commentary article, we explore the core functionalities of Blockchain applied to clinical trials and we illustrate concretely its general principle in the context of consent to a trial protocol. Trying to figure out the potential impact of Blockchain implementations in the setting of clinical trials will shed new light on how modern clinical trial methods could evolve and benefit from Blockchain technologies in order to tackle the aforementioned challenges.

Advancing the evidence base in cancer: psychosocial multicenter trials

PubMed Central

2012-01-01

Background The diagnosis and treatment of cancer is associated with significant distress and psychosocial morbidity. Although psychosocial interventions have been developed in an attempt to improve psychosocial outcomes in cancer patients and survivors, there is continued debate about whether there is adequate high-level evidence to establish the effectiveness of these interventions. The evidence base is limited as a result of numerous challenges faced by those attempting to conduct psychosocial intervention trials within the health system. Barriers include insufficient participant recruitment, difficulty generalizing from single-trial studies, difficulty in building and managing research teams with multidisciplinary expertise, lack of research design expertise and a lack of incentives for researchers conducting intervention research. To strengthen the evidence base, more intervention studies employing methodologically rigorous research designs are necessary. Methods In order to advance the evidence base of interventions designed to improve psychosocial outcomes for cancer patients and survivors, we propose the formation of a collaborative trials group that conducts multicenter trials to test the effectiveness of such interventions. Results Establishment of such a group would improve the quality of the evidence base in psychosocial research in cancer patients, by increasing support for conducting intervention research and providing intervention research training opportunities. A multidisciplinary collaborative group conducting multicenter trials would have the capacity to overcome many of the barriers that currently exist. Conclusions A stronger evidence base is necessary to identify effective psychosocial interventions for cancer patients. The proposed formation of a psycho-oncology collaborative trials group that conducts multicenter trials to test the effectiveness of psychosocial interventions would assist in achieving this outcome. PMID:22992443

The interaction between the spatial distribution of resource patches and population density: consequences for intraspecific growth and morphology.

PubMed

Jacobson, Bailey; Grant, James W A; Peres-Neto, Pedro R

2015-07-01

How individuals within a population distribute themselves across resource patches of varying quality has been an important focus of ecological theory. The ideal free distribution predicts equal fitness amongst individuals in a 1 : 1 ratio with resources, whereas resource defence theory predicts different degrees of monopolization (fitness variance) as a function of temporal and spatial resource clumping and population density. One overlooked landscape characteristic is the spatial distribution of resource patches, altering the equitability of resource accessibility and thereby the effective number of competitors. While much work has investigated the influence of morphology on competitive ability for different resource types, less is known regarding the phenotypic characteristics conferring relative ability for a single resource type, particularly when exploitative competition predominates. Here we used young-of-the-year rainbow trout (Oncorhynchus mykiss) to test whether and how the spatial distribution of resource patches and population density interact to influence the level and variance of individual growth, as well as if functional morphology relates to competitive ability. Feeding trials were conducted within stream channels under three spatial distributions of nine resource patches (distributed, semi-clumped and clumped) at two density levels (9 and 27 individuals). Average trial growth was greater in high-density treatments with no effect of resource distribution. Within-trial growth variance had opposite patterns across resource distributions. Here, variance decreased at low-population, but increased at high-population densities as patches became increasingly clumped as the result of changes in the levels of interference vs. exploitative competition. Within-trial growth was related to both pre- and post-trial morphology where competitive individuals were those with traits associated with swimming capacity and efficiency: larger heads/bodies/caudal fins and less angled pectoral fins. The different degrees of within-population growth variance at the same density level found here, as a function of spatial resource distribution, provide an explanation for the inconsistencies in within-site growth variance and population regulation often noted with regard to density dependence in natural landscapes. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Preoperative versus postoperative ultrasound-guided rectus sheath block for improving pain, sleep quality and cytokine levels of patients with open midline incisions undergoing transabdominal gynaecological operation: study protocol for a randomised controlled trial.

PubMed

Jin, Feng; Li, Xiao-Qian; Tan, Wen-Fei; Ma, Hong; Lu, Huang-Wei

2015-12-10

Rectus sheath block (RSB) is used for postoperative pain relief in patients undergoing abdominal surgery with midline incision. Preoperative RSB has been shown to be effective, but it has not been compared with postoperative RSB. The aim of the present study is to evaluate postoperative pain, sleep quality and changes in the cytokine levels of patients undergoing gynaecological surgery with RSB performed preoperatively versus postoperatively. This study is a prospective, randomised, controlled (randomised, parallel group, concealed allocation), single-blinded trial. All patients undergoing transabdominal gynaecological surgery will be randomised 1:1 to the treatment intervention with general anaesthesia as an adjunct to preoperative or postoperative RSB. The objective of the trial is to evaluate postoperative pain, sleep quality and changes in the cytokine levels of patients undergoing gynaecological surgery with RSB performed preoperatively (n = 32) versus postoperatively (n = 32). All of the patients, irrespective of group allocation, will receive patient-controlled intravenous analgesia (PCIA) with oxycodone. The primary objective is to compare the interval between leaving the post-anaesthesia care unit and receiving the first PCIA bolus injection on the first postoperative night between patients who receive preoperative versus postoperative RSB. The secondary objectives will be to compare (1) cumulative oxycodone consumption at 24 hours after surgery; (2) postoperative sleep quality, as measured using a BIS-Vista monitor during the first night after surgery; and (3) cytokine levels (interleukin-1, interleukin-6, tumour necrosis factor-α and interferon-γ) during surgery and at 24 and 48 hours postoperatively. Clinical experience has suggested that RSB is a very effective postoperative analgesic technique, and we will answer the following questions with this trial. Do preoperative block and postoperative block have the same duration of analgesic effects? Can postoperative block extend the analgesic time? The results of this study could have actual clinical applications that could help to reduce postoperative pain and shorten hospital stays. Current Controlled Trials NCT02477098 15 June 2015.

Industrial application of selected lactic acid bacteria isolated from local semolinas for typical sourdough bread production.

PubMed

Corona, Onofrio; Alfonzo, Antonio; Ventimiglia, Giusi; Nasca, Anna; Francesca, Nicola; Martorana, Alessandra; Moschetti, Giancarlo; Settanni, Luca

2016-10-01

Four obligate heterofermentative lactic acid bacteria (LAB) strains (Weissella cibaria PON10030 and PON10032 and Leuconostoc citreum PON 10079 and PON10080) were tested as single strain starters, mono-species dual strain starters, and multiple strain starter for the preparation and propagation of sourdoughs for the production of a typical bread at industrial level. The kinetics of pH and TTA during the daily sourdough refreshments indicated a correct acidification process for all trials. The concentration of lactic and acetic acid increased consistently during fermentation. The resulting molar ratios between these two organic acids in the experimental trials were lower than those observed in the control trial. The microbiological investigation showed levels of approximately 10(9) CFU/mL in almost all sourdoughs and the comparison of the genetic polymorphisms of the dominating LAB with those of the pure cultures evidenced the persistence of the added strains over time. The resulting breads were evaluated for several quality parameters. The breads with the greatest height were obtained with the quadruple combination of leuconostocs and weissellas. The highest softness was registered for the breads obtained from fermentations performed by W. cibaria PON10032 alone and in combination. The different inocula influenced also the color, the void fraction, the cell density and the mean cell area of the breads. Different levels of acids, alcohols, aldehydes, esters, hydrocarbons, ketones, terpenes, furans and phenol were emitted by the breads. The sensory tests indicated the breads from the sourdoughs fermented with the seven LAB inocula as sweeter and less acidic than control breads and the breads from the trials with the highest complexity of LAB inoculums were those more appreciated by tasters. A multivariate approach found strong differences among the trials. In particular, control breads and the breads obtained with different starter LAB were quite distant and a more strict relation was found among the productions carried out by W. cibaria strains. This study proved the suitability of the selected strains of L. citreum and W. cibaria for industrial-scale level applications in sourdough bread production. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of Danshen extract on lipoprotein-associated phospholipase A2 levels in patients with stable angina pectoris: study protocol for a randomized controlled trial - the DOLPHIN study.

PubMed

Chen, A-Di; Wang, Chun-Ling; Qin, Yang; Tian, Liang; Chen, Li-Bin; Yuan, Xiao-Ming; Ma, Lin-Xiu; Wang, Yu-Feng; Sun, Ji-Rong; Wang, Hao-Sen; Dai, Neng

2017-12-20

Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), a biomarker of oxidation and inflammation, has been associated with increased coronary artery disease risk. To date, very few studies have examined the Chinese herbal drug Danshen or its extract on Lp-PLA 2 in patients with stable angina pectoris. In this study, we aim to investigate the effect of Danshen extract on Lp-PLA 2 level in patients with stable angina. This is a randomized, single-blind, placebo-controlled, adaptive clinical trial. A total of 156 patients meeting the eligibility criteria will be randomly assigned to either the Danshen extract (DanshenDuofensuanyan injection and Danshen drop spill) group or the placebo group in a 1:1 ratio. Participants will then undergo treatment with DanshenDuofensuanyan injection or placebo (glucose) during hospitalization, followed by open-label Danshen drop spill (30 pills/day) in Danshen extract group for 60 days after discharge. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. On the basis of the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the serum level of Lp-PLA 2 in the Danshen extract group and the placebo group. The secondary outcomes include the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire and the carotid intima-media thickness, which will be measured using ultrasound. Other secondary efficacy and safety outcomes will also be assessed. This study will provide evidence that Danshen extract is beneficial for stable angina and may establish a possible mechanism of Danshen treatment effects on cardiovascular disease. This study may also validate an objective blood test (LP-PLA 2 level) for assessing the effectiveness of Danshen therapy in patients with stable angina pectoris. ClinicalTrials.gov, NCT02870764 . Registered on 13 August 2016.

The effects of reducing worry in patients with persecutory delusions: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Our approach to advancing the treatment of psychosis is to focus on key single symptoms and develop interventions that target the mechanisms that maintain them. In our theoretical research we have found worry to be an important factor in the development and maintenance of persecutory delusions. Worry brings implausible ideas to mind, keeps them there, and makes the experience distressing. Therefore the aim of the trial is to test the clinical efficacy of a cognitive-behavioral intervention for worry for patients with persecutory delusions and determine how the worry treatment might reduce delusions. Methods/Design An explanatory randomized controlled trial - called the Worry Intervention Trial (WIT) - with 150 patients with persecutory delusions will be carried out. Patients will be randomized to the worry intervention in addition to standard care or to standard care. Randomization will be carried out independently, assessments carried out single-blind, and therapy competence and adherence monitored. The study population will be individuals with persecutory delusions and worry in the context of a schizophrenia spectrum diagnosis. They will not have responded adequately to previous treatment. The intervention is a six-session cognitive-behavioral treatment provided over eight weeks. The control condition will be treatment as usual, which is typically antipsychotic medication and regular appointments. The principal hypotheses are that a worry intervention will reduce levels of worry and that it will also reduce the persecutory delusions. Assessments will be carried out at 0 weeks (baseline), 8 weeks (post treatment) and 24 weeks (follow-up). The statistical analysis strategy will follow the intention-to-treat principle and involve the use of linear mixed models to evaluate and estimate the relevant between- and within-subjects effects (allowing for the possibility of missing data). Both traditional regression and newer instrumental variables analyses will examine mediation. The trial is funded by the UK Medical Research Council (MRC)/NHS National Institute of Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) Programme. Discussion This will be the first large randomized controlled trial specifically focused upon persecutory delusions. The project will produce a brief, easily administered intervention that can be readily used in mental health services. Trial registration Current Controlled Trials ISRCTN23197625 PMID:23171601

Robust inference for group sequential trials.

PubMed

Ganju, Jitendra; Lin, Yunzhi; Zhou, Kefei

2017-03-01

For ethical reasons, group sequential trials were introduced to allow trials to stop early in the event of extreme results. Endpoints in such trials are usually mortality or irreversible morbidity. For a given endpoint, the norm is to use a single test statistic and to use that same statistic for each analysis. This approach is risky because the test statistic has to be specified before the study is unblinded, and there is loss in power if the assumptions that ensure optimality for each analysis are not met. To minimize the risk of moderate to substantial loss in power due to a suboptimal choice of a statistic, a robust method was developed for nonsequential trials. The concept is analogous to diversification of financial investments to minimize risk. The method is based on combining P values from multiple test statistics for formal inference while controlling the type I error rate at its designated value.This article evaluates the performance of 2 P value combining methods for group sequential trials. The emphasis is on time to event trials although results from less complex trials are also included. The gain or loss in power with the combination method relative to a single statistic is asymmetric in its favor. Depending on the power of each individual test, the combination method can give more power than any single test or give power that is closer to the test with the most power. The versatility of the method is that it can combine P values from different test statistics for analysis at different times. The robustness of results suggests that inference from group sequential trials can be strengthened with the use of combined tests. Copyright © 2017 John Wiley & Sons, Ltd.

Suicide Risk Assessment and Prevention: A Systematic Review Focusing on Veterans.

PubMed

Nelson, Heidi D; Denneson, Lauren M; Low, Allison R; Bauer, Brian W; O'Neil, Maya; Kansagara, Devan; Teo, Alan R

2017-10-01

Suicide rates in veteran and military populations in the United States are high. This article reviews studies of the accuracy of methods to identify individuals at increased risk of suicide and the effectiveness and adverse effects of health care interventions relevant to U.S. veteran and military populations in reducing suicide and suicide attempts. Trials, observational studies, and systematic reviews relevant to U.S. veterans and military personnel were identified in searches of MEDLINE, PsycINFO, SocINDEX, and Cochrane databases (January 1, 2008, to September 11, 2015), on Web sites, and in reference lists. Investigators extracted and confirmed data and dual-rated risk of bias for included studies. Nineteen studies evaluated accuracy of risk assessment methods, including models using retrospective electronic records data and clinician- or patient-rated instruments. Most methods demonstrated sensitivity ≥80% or area-under-the-curve values ≥.70 in single studies, including two studies based on electronic records of veterans and military personnel, but specificity varied. Suicide rates were reduced in six of eight observational studies of population-level interventions. Only two of ten trials of individual-level psychotherapy reported statistically significant differences between treatment and usual care. Risk assessment methods have been shown to be sensitive predictors of suicide and suicide attempts, but the frequency of false positives limits their clinical utility. Research to refine these methods and examine clinical applications is needed. Studies of suicide prevention interventions are inconclusive; trials of population-level interventions and promising therapies are required to support their clinical use.

Systems Biology Methods for Alzheimer's Disease Research Toward Molecular Signatures, Subtypes, and Stages and Precision Medicine: Application in Cohort Studies and Trials.

PubMed

Castrillo, Juan I; Lista, Simone; Hampel, Harald; Ritchie, Craig W

2018-01-01

Alzheimer's disease (AD) is a complex multifactorial disease, involving a combination of genomic, interactome, and environmental factors, with essential participation of (a) intrinsic genomic susceptibility and (b) a constant dynamic interplay between impaired pathways and central homeostatic networks of nerve cells. The proper investigation of the complexity of AD requires new holistic systems-level approaches, at both the experimental and computational level. Systems biology methods offer the potential to unveil new fundamental insights, basic mechanisms, and networks and their interplay. These may lead to the characterization of mechanism-based molecular signatures, and AD hallmarks at the earliest molecular and cellular levels (and beyond), for characterization of AD subtypes and stages, toward targeted interventions according to the evolving precision medicine paradigm. In this work, an update on advanced systems biology methods and strategies for holistic studies of multifactorial diseases-particularly AD-is presented. This includes next-generation genomics, neuroimaging and multi-omics methods, experimental and computational approaches, relevant disease models, and latest genome editing and single-cell technologies. Their progressive incorporation into basic research, cohort studies, and trials is beginning to provide novel insights into AD essential mechanisms, molecular signatures, and markers toward mechanism-based classification and staging, and tailored interventions. Selected methods which can be applied in cohort studies and trials, with the European Prevention of Alzheimer's Dementia (EPAD) project as a reference example, are presented and discussed.

A prospective picture collection study for a grading atlas of radiation dermatitis for clinical trials in head-and-neck cancer patients

PubMed Central

Zenda, Sadamoto; Ota, Yosuke; Tachibana, Hiroyuki; Ogawa, Hirofumi; Ishii, Shinobu; Hashiguchi, Chikako; Akimoto, Tetsuo; Ohe, Yuichiro; Uchitomi, Yosuke

2016-01-01

Radiation dermatitis is one of the most common acute toxicities of both radiotherapy and chemoradiotherapy. Many clinical trials have evaluated the level of toxicity using the Common Terminology Criteria for Adverse Events ver. 4.03. This criterion accounts for severity in a single sentence only, and no visual classification guide has been available. Thus, there is a risk of subjective interpretation by the individual investigator. This contrasts with the situation with hematologic toxicities, which can be interpreted objectively. The aim of this prospective picture collection study was to develop a grading tool for use in establishing the severity of radiation dermatitis in clinical trials. A total of 118 patients who were scheduled to receive definitive or postoperative radiotherapy or chemoradiotherapy were enrolled from the four participating cancer centers. All researchers in our group used the same model of camera under the same shooting conditions to maintain consistent photographic quality. In all, 1600 photographs were collected. Of these, 100 photographs qualified for the first round of selection and were then graded by six experts, basically in accordance with the CTCAE ver. 4.03 (JCOG ver. in Japanese). After further study, 38 photographs were selected as representing typical models for Grade 1–4 radiation dermatitis; the radiation dermatitis grading atlas was produced from these photographs. The atlas will play a major role in ensuring that the dermatitis rating system is consistent between the institutions participating in trials. We hope that this will contribute to improving the quality of clinical trials, and also to improving the level of routine clinical practice. PMID:26850926

Comparison of the benefits of cochlear implantation versus contra-lateral routing of signal hearing aids in adult patients with single-sided deafness: study protocol for a prospective within-subject longitudinal trial

PubMed Central

2014-01-01

Background Individuals with a unilateral severe-to-profound hearing loss, or single-sided deafness, report difficulty with listening in many everyday situations despite having access to well-preserved acoustic hearing in one ear. The standard of care for single-sided deafness available on the UK National Health Service is a contra-lateral routing of signals hearing aid which transfers sounds from the impaired ear to the non-impaired ear. This hearing aid has been found to improve speech understanding in noise when the signal-to-noise ratio is more favourable at the impaired ear than the non-impaired ear. However, the indiscriminate routing of signals to a single ear can have detrimental effects when interfering sounds are located on the side of the impaired ear. Recent published evidence has suggested that cochlear implantation in individuals with a single-sided deafness can restore access to the binaural cues which underpin the ability to localise sounds and segregate speech from other interfering sounds. Methods/Design The current trial was designed to assess the efficacy of cochlear implantation compared to a contra-lateral routing of signals hearing aid in restoring binaural hearing in adults with acquired single-sided deafness. Patients are assessed at baseline and after receiving a contra-lateral routing of signals hearing aid. A cochlear implant is then provided to those patients who do not receive sufficient benefit from the hearing aid. This within-subject longitudinal design reflects the expected care pathway should cochlear implantation be provided for single-sided deafness on the UK National Health Service. The primary endpoints are measures of binaural hearing at baseline, after provision of a contra-lateral routing of signals hearing aid, and after cochlear implantation. Binaural hearing is assessed in terms of the accuracy with which sounds are localised and speech is perceived in background noise. The trial is also designed to measure the impact of the interventions on hearing- and health-related quality of life. Discussion This multi-centre trial was designed to provide evidence for the efficacy of cochlear implantation compared to the contra-lateral routing of signals. A purpose-built sound presentation system and established measurement techniques will provide reliable and precise measures of binaural hearing. Trial registration Current Controlled Trials http://www.controlled-trials.com/ISRCTN33301739 (05/JUL/2013) PMID:25152694

Study protocol for a randomised controlled multicentre study: the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) in patients with cervical radiculopathy.

PubMed

Broekema, A E H; Kuijlen, J M A; Lesman-Leegte, G A T; Bartels, R H M A; van Asselt, A D I; Vroomen, P C A J; van Dijk, J M C; Reneman, M F; Soer, R; Groen, R J M

2017-01-05

Cervical radiculopathy due to discogenic or spondylotic stenosis of the neuroforamen can be surgically treated by an anterior discectomy with fusion (ACDF) or a posterior foraminotomy (FOR). Most surgeons prefer ACDF, although there are indications that FOR is as effective as ACDF, has a lower complication rate and is less expensive. A head-to-head comparison of the 2 surgical techniques in a randomised controlled trial has not yet been performed. The study objectives of the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) study are to compare clinical outcomes, complication rates and cost-effectiveness of FOR to ACDF. The FACET study is a prospective randomised controlled trial conducted in 7 medical centres in the Netherlands. The follow-up period is 2 years. The main inclusion criterion is a radiculopathy of the C4, C5, C6 or C7 nerve root, due to a single-level isolated cervical foraminal stenosis caused by a soft disc and/or osteophytic component, requiring operative decompression. A sample size of 308 patients is required to test the hypothesis of clinical non-inferiority of FOR versus ACDF. Primary outcomes are: 'operative success', the measured decrease in radiculopathy assessed by the visual analogue scale and 'patient success', assessed by the modified Odom's criteria. Secondary outcomes are: Work Ability Index (single-item WAI), quality of life (EuroQol 5 Dimensions 5 level Survey, EQ-5D-5L), Neck Disability Index (NDI) and complications. An economic evaluation will assess cost-effectiveness. In addition, a budget impact analysis will be performed. Ethical approval was obtained from the Institutional Ethics Committee of the University Medical Center Groningen. Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. NTR5536, pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Stemming the Tide of Antibiotic Resistance (STAR): a protocol for a trial of a complex intervention addressing the 'why' and 'how' of appropriate antibiotic prescribing in general practice.

PubMed

Simpson, Sharon A; Butler, Christopher C; Hood, Kerry; Cohen, David; Dunstan, Frank; Evans, Meirion R; Rollnick, Stephen; Moore, Laurence; Hare, Monika; Bekkers, Marie-Jet; Evans, John

2009-03-23

After some years of a downward trend, antibiotic prescribing rates in the community have tended to level out in many countries. There is also wide variation in antibiotic prescribing between general practices, and between countries. There are still considerable further gains that could be made in reducing inappropriate antibiotic prescribing, but complex interventions are required. Studies to date have generally evaluated the effect of interventions on antibiotic prescribing in a single consultation and pragmatic evaluations that assess maintenance of new skills are rare. This paper describes the protocol for a pragmatic, randomized evaluation of a complex intervention aimed at reducing antibiotic prescribing by primary care clinicians. We developed a Social Learning Theory based, blended learning program (on-line learning, a practice based seminar, and context bound learning) called the STAR Educational Program. The 'why of change' is addressed by providing clinicians in general practice with information on antibiotic resistance in urine samples submitted by their practice and their antibiotic prescribing data, and facilitating a practice-based seminar on the implications of this data. The 'how of change' is addressed through context-bound communication skills training and information on antibiotic indication and choice. This intervention will be evaluated in a trial involving 60 general practices, with general practice as the unit of randomization (clinicians from each practice to either receive the STAR Educational Program or not) and analysis. The primary outcome will be the number of antibiotic items dispensed over one year. An economic and process evaluation will also be conducted. This trial will be the first to evaluate the effectiveness of this type of theory-based, blended learning intervention aimed at reducing antibiotic prescribing by primary care clinicians. Novel aspects include feedback of practice level data on antimicrobial resistance and prescribing, use of principles from motivational interviewing, training in enhanced communication skills that incorporates context-bound experience and reflection, and using antibiotic dispensing over one year (as opposed to antibiotic prescribing in a single consultation) as the main outcome. Current Controlled Trials ISRCTN63355948.

Effect of a Mediterranean diet on endothelial progenitor cells and carotid intima-media thickness in type 2 diabetes: Follow-up of a randomized trial.

PubMed

Maiorino, Maria Ida; Bellastella, Giuseppe; Petrizzo, Michela; Gicchino, Maurizio; Caputo, Mariangela; Giugliano, Dario; Esposito, Katherine

2017-03-01

Background We assessed the long-term effects of a Mediterranean diet on circulating levels of endothelial progenitor cells (EPCs) and the carotid intima-media thickness (CIMT) in patients with type 2 diabetes. Design This was a parallel, two-arm, single-centre trial. Methods Two hundred and fifteen men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet ( n = 108) or a low-fat diet ( n = 107). The primary outcome measures were changes in the EPC count and the CIMT of the common carotid artery after the treatment period defined as the end of trial (EOT). Results At the EOT, both the CD34 + KDR + and CD34 + KDR + CD133 + counts had increased with the Mediterranean diet compared with the low-fat diet ( p < 0.05 for both). At the EOT evaluation, there was a significant ( p = 0.024) difference of -0.025 mm in the CIMT favouring the Mediterranean diet. Compared with the low-fat diet, the rate of regression in the CIMT was higher in the Mediterranean diet group (51 vs. 26%), whereas the rate of progression was lower (25 vs. 50%) ( p = 0.032 for both). Changes in the CIMT were inversely correlated with the changes in EPC levels (CD34 + KDR + , r = -0.24, p = 0.020; CD34 + KDR + CD133 + , r = -0.28, p = 0.014). At the EOT, changes in levels of HbA1c, HOMA, total cholesterol, high-density lipoprotein cholesterol and systolic blood pressure were significantly greater with the Mediterranean diet than with the low-fat diet. Conclusion Compared with a low-fat diet, a long-term trial with Mediterranean diet was associated with an increase in circulating EPCs levels and prevention of the progression of subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes.

Effect of low-dose spironolactone on resistant hypertension in type 2 diabetes mellitus: a randomized controlled trial in a sub-Saharan African population.

PubMed

Djoumessi, Romance Nguetse; Noubiap, Jean Jacques N; Kaze, Francois Folefack; Essouma, Mickael; Menanga, Alain Patrick; Kengne, Andre Pascal; Mbanya, Jean Claude; Sobngwi, Eugene

2016-03-23

Low-dose spironolactone has been proven to be effective for resistant hypertension in the general population, but this has yet to be confirmed in type 2 diabetic (T2DM) patients. We assessed the efficacy of a low-dose spironolactone on resistant hypertension in a sub-Saharan African population of T2DM patients from Cameroon. This was a four-week single blinded randomized controlled trial in 17 subjects presenting with resistant hypertension in specialized diabetes care units in Cameroon. They were randomly assigned to treatment with a daily 25 mg of spironolactone (n = 9) or to an alternative antihypertensive regimen (n = 8), on top of any ongoing regimen and prevailing lifestyle prescriptions. They were seen at the start of the treatment, then 2 and 4 weeks later. The primary outcome was change in office and self-measured blood pressure (BP) during follow-up, and secondary outcomes were changes in serum potassium, sodium, and creatinine levels. Compared with alternative treatment, low-dose spironolactone was associated with significant decrease in office systolic BP (-33 vs. -14 mmHg; p = 0.024), and in diastolic BP (-14 vs. -5 mmHg; p = 0.006). After 1 month of spironolactone, all the patients were controlled based on BP below 130/80 mmHg, with significant office BP reduction from 158 ± 17/86 ± 11 to 125 ± 11/72 ± 8, vs. 158 ± 8/94 ± 8 to 144 ± 17/89 ± 12 mmHg in the alternative treatment group. There was no significant variation in sodium and creatinine levels in both groups, but a mild increase of potassium levels in the spironolactone group. Add-on low-dose spironolactone was effective in reducing BP to optimal levels in T2DM Cameroonian patients despite mild increase in serum potassium. Trial registration ClinicalTrials.gov Identifier NCT02426099. Date of registration April 2015.

Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis.

PubMed

Takahashi, S; Katada, J; Daida, H; Kitamura, F; Yokoyama, K

2016-09-01

Blood pressure (BP) control is important to ameliorate cardiovascular events in patients with diabetes mellitus (DM). However, achieving the target BP with a single drug is often difficult. The objective of this study was to evaluate the antihypertensive effects of mineralocorticoid receptor antagonists (MRAs) as add-on therapy to renin-angiotensin system (RAS) inhibitor(s) in patients with hypertension and DM. Studies were searched through October 2014 in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Randomized, controlled trials or prospective, observational studies regarding concomitant administration of MRA and RAS inhibitor(s) in patients with DM were included. Articles were excluded if the mean systolic BP (SBP) was <130 mm Hg before randomization for interventional studies or at baseline for prospective cohort studies. We identified nine eligible studies (486 patients): five randomized placebo-controlled trials; three randomized active drug-controlled trials; and one single-arm observational study. The mean differences in office SBP and diastolic BP (DBP) between the MRA and placebo groups were -9.4 (95% confidence interval (CI) -12.9 to -5.9) and -3.8 (95% CI, -5.5 to -2.2) mm Hg, respectively. Subgroup analysis results for study type, age, baseline office SBP and follow-up duration were similar to those of the main analysis. MRA mildly increased serum potassium (0.4 mEq l(-1); 95% CI, 0.3-0.5 mEq l(-1)). A consistent reduction of albuminuria across these studies was also demonstrated. MRA further reduced SBP and DBP in patients with hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia.

A Multiinstitutional Phase 2 Trial of Pazopanib Monotherapy in Advanced Anaplastic Thyroid Cancer

PubMed Central

Suman, Vera J.; Menefee, Michael E.; Smallridge, Robert C.; Molina, Julian R.; Maples, William J.; Karlin, Nina J.; Traynor, Anne M.; Kumar, Priya; Goh, Boon Cher; Lim, Wan-Teck; Bossou, Ayoko R.; Isham, Crescent R.; Webster, Kevin P.; Kukla, Andrea K.; Bieber, Carolyn; Burton, Jill K.; Harris, Pamela; Erlichman, Charles

2012-01-01

Context/Objectives: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC). Design/Setting/Patients/Interventions/Outcome Measures: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response. Results: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45–77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease. Conclusions: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC. PMID:22774206

Relative and absolute reliability of the clinical version of the Narrow Path Walking Test (NPWT) under single and dual task conditions.

PubMed

Gimmon, Yoav; Jacob, Grinshpon; Lenoble-Hoskovec, Constanze; Büla, Christophe; Melzer, Itshak

2013-01-01

Decline in gait stability has been associated with increased fall risk in older adults. Reliable and clinically feasible methods of gait instability assessment are needed. This study evaluated the relative and absolute reliability and concurrent validity of the testing procedure of the clinical version of the Narrow Path Walking Test (NPWT) under single task (ST) and dual task (DT) conditions. Thirty independent community-dwelling older adults (65-87 years) were tested twice. Participants were instructed to walk within the 6-m narrow path without stepping out. Trial time, number of steps, trial velocity, number of step errors, and number of cognitive task errors were determined. Intraclass correlation coefficients (ICCs) were calculated as indices of agreement, and a graphic approach called "mountain plot" was applied to help interpret the direction and magnitude of disagreements between testing procedures. Smallest detectable change and smallest real difference (SRD) were computed to determine clinically relevant improvement at group and individual levels, respectively. Concurrent validity was assessed using Performance Oriented Mobility Assessment Tool (POMA) and the Short Physical Performance Battery (SPPB). Test-retest agreement (ICC1,2) varied from 0.77 to 0.92 in ST and from 0.78 to 0.92 in DT conditions, with no apparent systematic differences between testing procedures demonstrated by the mountain plot graphs. Smallest detectable change and smallest real change were small for motor task performance and larger for cognitive errors. Significant correlations were observed for trial velocity and trial time with POMA and SPPB. The present results indicate that the NPWT testing procedure is highly reliable and reproducible. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Prospective trial of an herbal formula BYSH and Saw palmetto in patients with hormonal refractory prostate cancer: a pilot study.

PubMed

Ng, Anthony C-F; Cheng, K-F; Leung, P-C

2014-01-01

BYSH, a herbal formula, was evaluated for efficacy and safety in a pilot study for patients with advanced hormone refractory prostate cancer (HRPC). The pilot study was designed as a single-center open-label trial. Patients with HRPC were treated with BYSH for 24 weeks. The primary end point was the changes in serum prostate-specific antigen (PSA) level. Safety parameters such as liver and renal functions were monitored during the study period. Ten patients were eligible for the study. Most of them had stable PSA levels while taking BYSH. However, at the end of the BYSH treatment, the level of PSA increased. The median survival from diagnosis of HRPC was 16.4 months. Liver and renal functions remained normal. BYSH was well tolerated and no patient reported adverse events during the study period. Although it is inappropriate to make a conclusion based on the pilot study results, the trend of improvement is obvious. Further investigations should be conducted to demonstrate its clinical benefits. We have also briefly reviewed some plant products which are patented and also available in market.

Laser in Glaucoma and Ocular Hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology.

PubMed

Gazzard, Gus; Konstantakopoulou, Evgenia; Garway-Heath, David; Barton, Keith; Wormald, Richard; Morris, Stephen; Hunter, Rachael; Rubin, Gary; Buszewicz, Marta; Ambler, Gareth; Bunce, Catey

2018-05-01

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. ISRCTN32038223, Pre-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.

Single-trial classification of motor imagery differing in task complexity: a functional near-infrared spectroscopy study

PubMed Central

2011-01-01

Background For brain computer interfaces (BCIs), which may be valuable in neurorehabilitation, brain signals derived from mental activation can be monitored by non-invasive methods, such as functional near-infrared spectroscopy (fNIRS). Single-trial classification is important for this purpose and this was the aim of the presented study. In particular, we aimed to investigate a combined approach: 1) offline single-trial classification of brain signals derived from a novel wireless fNIRS instrument; 2) to use motor imagery (MI) as mental task thereby discriminating between MI signals in response to different tasks complexities, i.e. simple and complex MI tasks. Methods 12 subjects were asked to imagine either a simple finger-tapping task using their right thumb or a complex sequential finger-tapping task using all fingers of their right hand. fNIRS was recorded over secondary motor areas of the contralateral hemisphere. Using Fisher's linear discriminant analysis (FLDA) and cross validation, we selected for each subject a best-performing feature combination consisting of 1) one out of three channel, 2) an analysis time interval ranging from 5-15 s after stimulation onset and 3) up to four Δ[O2Hb] signal features (Δ[O2Hb] mean signal amplitudes, variance, skewness and kurtosis). Results The results of our single-trial classification showed that using the simple combination set of channels, time intervals and up to four Δ[O2Hb] signal features comprising Δ[O2Hb] mean signal amplitudes, variance, skewness and kurtosis, it was possible to discriminate single-trials of MI tasks differing in complexity, i.e. simple versus complex tasks (inter-task paired t-test p ≤ 0.001), over secondary motor areas with an average classification accuracy of 81%. Conclusions Although the classification accuracies look promising they are nevertheless subject of considerable subject-to-subject variability. In the discussion we address each of these aspects, their limitations for future approaches in single-trial classification and their relevance for neurorehabilitation. PMID:21682906

Multi-Tasking and Choice of Training Data Influencing Parietal ERP Expression and Single-Trial Detection-Relevance for Neuroscience and Clinical Applications.

PubMed

Kirchner, Elsa A; Kim, Su Kyoung

2018-01-01

Event-related potentials (ERPs) are often used in brain-computer interfaces (BCIs) for communication or system control for enhancing or regaining control for motor-disabled persons. Especially results from single-trial EEG classification approaches for BCIs support correlations between single-trial ERP detection performance and ERP expression. Hence, BCIs can be considered as a paradigm shift contributing to new methods with strong influence on both neuroscience and clinical applications. Here, we investigate the relevance of the choice of training data and classifier transfer for the interpretability of results from single-trial ERP detection. In our experiments, subjects performed a visual-motor oddball task with motor-task relevant infrequent ( targets ), motor-task irrelevant infrequent ( deviants ), and motor-task irrelevant frequent ( standards ) stimuli. Under dual-task condition, a secondary senso-motor task was performed, compared to the simple-task condition. For evaluation, average ERP analysis and single-trial detection analysis with different numbers of electrodes were performed. Further, classifier transfer was investigated between simple and dual task. Parietal positive ERPs evoked by target stimuli (but not by deviants) were expressed stronger under dual-task condition, which is discussed as an increase of task emphasis and brain processes involved in task coordination and change of task set. Highest classification performance was found for targets irrespective whether all 62, 6 or 2 parietal electrodes were used. Further, higher detection performance of targets compared to standards was achieved under dual-task compared to simple-task condition in case of training on data from 2 parietal electrodes corresponding to results of ERP average analysis. Classifier transfer between tasks improves classification performance in case that training took place on more varying examples (from dual task). In summary, we showed that P300 and overlaying parietal positive ERPs can successfully be detected while subjects are performing additional ongoing motor activity. This supports single-trial detection of ERPs evoked by target events to, e.g., infer a patient's attentional state during therapeutic intervention.

Multi-Tasking and Choice of Training Data Influencing Parietal ERP Expression and Single-Trial Detection—Relevance for Neuroscience and Clinical Applications

PubMed Central

Kirchner, Elsa A.; Kim, Su Kyoung

2018-01-01

Event-related potentials (ERPs) are often used in brain-computer interfaces (BCIs) for communication or system control for enhancing or regaining control for motor-disabled persons. Especially results from single-trial EEG classification approaches for BCIs support correlations between single-trial ERP detection performance and ERP expression. Hence, BCIs can be considered as a paradigm shift contributing to new methods with strong influence on both neuroscience and clinical applications. Here, we investigate the relevance of the choice of training data and classifier transfer for the interpretability of results from single-trial ERP detection. In our experiments, subjects performed a visual-motor oddball task with motor-task relevant infrequent (targets), motor-task irrelevant infrequent (deviants), and motor-task irrelevant frequent (standards) stimuli. Under dual-task condition, a secondary senso-motor task was performed, compared to the simple-task condition. For evaluation, average ERP analysis and single-trial detection analysis with different numbers of electrodes were performed. Further, classifier transfer was investigated between simple and dual task. Parietal positive ERPs evoked by target stimuli (but not by deviants) were expressed stronger under dual-task condition, which is discussed as an increase of task emphasis and brain processes involved in task coordination and change of task set. Highest classification performance was found for targets irrespective whether all 62, 6 or 2 parietal electrodes were used. Further, higher detection performance of targets compared to standards was achieved under dual-task compared to simple-task condition in case of training on data from 2 parietal electrodes corresponding to results of ERP average analysis. Classifier transfer between tasks improves classification performance in case that training took place on more varying examples (from dual task). In summary, we showed that P300 and overlaying parietal positive ERPs can successfully be detected while subjects are performing additional ongoing motor activity. This supports single-trial detection of ERPs evoked by target events to, e.g., infer a patient's attentional state during therapeutic intervention. PMID:29636660

The Tendril Plot-a novel visual summary of the incidence, significance and temporal aspects of adverse events in clinical trials.

PubMed

Karpefors, Martin; Weatherall, James

2018-03-21

In contrast to efficacy, safety hypotheses of clinical trials are not always pre-specified, and therefore, the safety interpretation work of a trial tends to be more exploratory, often reactive, and the analysis more statistically and graphically challenging. We introduce a new means of visualizing the adverse event data across an entire clinical trial. The approach overcomes some of the current limitations of adverse event analysis and streamlines the way safety data can be explored, interpreted and analyzed. Using a phase II study, we describe and exemplify how the tendril plot effectively summarizes the time-resolved safety profile of two treatment arms in a single plot and how that can provide scientists with a trial safety overview that can support medical decision making. To our knowledge, the tendril plot is the only way to graphically show important treatment differences with preserved temporal information, across an entire clinical trial, in a single view.

Number of embryos for transfer following in-vitro fertilisation or intra-cytoplasmic sperm injection.

PubMed

Pandian, Z; Bhattacharya, S; Ozturk, O; Serour, G I; Templeton, A

2004-10-18

The traditional reliance on the transfer of multiple embryos during in vitro fertilisation (IVF) in order to maximise the chance of pregnancy, has resulted in increasing rates of multiple pregnancies. Women undergoing IVF had a 20 - fold increased risk of twins and 400 - fold increased risk of higher order pregnancies (Martin 1998). The maternal and perinatal morbidity and mortality as well as national health service costs associated with multiple pregnancies is significantly high in comparison with singleton births (Luke 1992; Callahan 1994; Goldfarb 1996). Single embryo transfer is now being considered as an effective means of reducing this iatrogenic complication. This systematic review evaluates the effectiveness of elective two embryo transfer in comparison with single and more than two embryo transfer following IVF and ICSI (intra cytoplasmic sperm injection) treatment. The aim of this review is to determine, whether in couples who undergo IVF/ICSI: (1) the elective transfer of two embryos improves the probability of livebirth compared with: (a) Single embryo transfer, (b) Three embryo transfer or (c) Four embryo transfer.(2) the elective transfer of three embryos improves the probability of livebirth compared with: (a) Single embryo transfer, or (b) Four embryo transfer, We searched the Cochrane Menstrual Disorders and Subfertility Group's trials register (searched June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (1970 to 2003), EMBASE (1985 to 2003) and reference lists of articles. We also handsearched relevant conference proceedings and contacted researchers in the field. Only randomised controlled trials were included. Two reviewers independently assessed eligibility and quality of trials. We found no studies that compared a policy of transferring multiple embryos on one cycle versus a policy of cryo- preservation and transfer of a single embryo over multiple cycles. We also found no trials comparing transfer of two versus three embryos. Three small, poorly reported trials compared transfer of two versus one embryo in a single cycle, and one small, poorly reported trial compared transfer of two versus four embryos in a single cycle. The clinical pregnancy rate per woman/couple associated with two embryo transfer was significantly higher compared to single embryo transfer (OR 2.08, 95% CI 1.24 to 3.50; test for overall effect p = 0.006). The live birth rate per woman/couple associated with two embryo transfer was also significantly higher than that associated with single embryo transfer (OR 1.90, 95% CI 1.12 to 3.22, test for overall effect p=0.02). The multiple pregnancy rate was significantly lower in women who had single embryo transfer (OR 9.97, 95% CI 2.61 to 38.19; p = 0.0008). The effectiveness of double embryo transfer versus four embryo transfer was tested in a single trial. There was no statistically significant differences in the clinical pregnancy rate (OR 0.75, 95% CI 0.26 to 2.16; p=0.6), and multiple pregnancy rates (OR 0.44. 95% CI 0.10 to 1.97; p = 0.28) between the two groups. The livebirth rate in the four embryo transfer group was higher compared to the two embryo transfer group, but the results were not statistically significant (OR 0.35, 95% CI 0.11 to 1.05; p = 0.06). The results of this systematic review suggest that live birth and pregnancy rates following single embryo transfer are lower than those following double embryo transfer as are the chances of multiple pregnancy including twins. As such, it is unlikely that the conclusions are robust enough to catalyse a change in clinical practice. The studies included are limited by their small sample size, so that even large differences might be hidden. Cumulative livebirth rates are seldom reported. The data were inadequate to draw conclusions about single embryo transfer and first frozen single embryo transfer (1FZET) or subsequent single frozen embryo transfers. Until more evidence is available single embryo transfer may not be the preferred choice for all patients undergoing IVF/ICSI. Clinicians may need to individualise protocols for couples based on their risks of multiple pregnancy. A definitive pragmatic, large multi centre randomised controlled trial comparing single embryo versus double embryo transfer in terms of clinical and cost effectiveness as well as acceptability is required. The primary outcome measured should be cumulative livebirth per woman/couple.

Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial.

PubMed

Mathiassen, Ole N; Vase, Henrik; Bech, Jesper N; Christensen, Kent L; Buus, Niels H; Schroeder, Anne P; Lederballe, Ole; Rickers, Hans; Kampmann, Ulla; Poulsen, Per L; Hansen, Klavs W; Btker, Hans E; Peters, Christian D; Engholm, Morten; Bertelsen, Jannik B; Lassen, Jens F; Langfeldt, Sten; Andersen, Gratien; Pedersen, Erling B; Kaltoft, Anne

2016-08-01

Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ± 18.8 mmHg (RDN) vs. -6.0 ± 13.5 mmHg (SHAM)] and at 6 months [-6.1 ± 18.9 mmHg (RDN) vs. -4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

Meeting the Challenge: The National Cancer Institute's Central Institutional Review Board for Multi-Site Research.

PubMed

Massett, Holly A; Hampp, Sharon L; Goldberg, Jacquelyn L; Mooney, Margaret; Parreco, Linda K; Minasian, Lori; Montello, Mike; Mishkin, Grace E; Davis, Catasha; Abrams, Jeffrey S

2018-03-10

The National Institutes of Health (NIH) issued a new policy that requires a single institutional review board (IRB) of record be used for all protocols funded by the NIH that are carried out at more than one site in the United States, effective January 2018. This policy affects several hundred clinical trials opened annually across the NIH. Limited data exist to compare the use of a single IRB to that of multiple local IRBs, so some institutions are resistant to or distrustful of single IRBs. Since 2001, the National Cancer Institute (NCI) has funded a central IRB (CIRB) that provides human patient reviews for its extensive national cancer clinical trials program. This paper presents data to show the adoption, efficiencies gained, and satisfaction of the CIRB among NCI trial networks and reviews key lessons gleaned from 16 years of experience that may be informative for others charged with implementation of the new NIH single-IRB policy.

The effectiveness of wellness coaching for improving quality of life.

PubMed

Clark, Matthew M; Bradley, Karleah L; Jenkins, Sarah M; Mettler, Emily A; Larson, Brent G; Preston, Heather R; Liesinger, Juliette T; Werneburg, Brooke L; Hagen, Philip T; Harris, Ann M; Riley, Beth A; Olsen, Kerry D; Vickers Douglas, Kristin S

2014-11-01

To learn more about the potential psychosocial benefits of wellness coaching. Although wellness coaching is increasing in popularity, there are few published outcome studies. In a single-cohort study design, 100 employees who completed the 12-week wellness coaching program were of a mean age of 42 years, 90% were women, and most were overweight or obese. Three areas of psychosocial functioning were assessed: quality of life (QOL; 5 domains and overall), depressive symptoms (Patient Health Questionnaire-9), and perceived stress level (Perceived Stress Scale-10). Participants were recruited from January 1, 2011, through December 31, 2011; data were collected up to July 31, 2012, and were analyzed from August 1, 2012, through October 31, 2013. These 100 wellness coaching completers exhibited significant improvements in all 5 domains of QOL and overall QOL (P<.0001), reduced their level of depressive symptoms (P<.0001), and reduced their perceived stress level (P<.001) after 12 weeks of in-person wellness coaching, and they maintained these improvements at the 24-week follow-up. In this single-arm cohort study (level 2b evidence), participating in wellness coaching was associated with improvement in 3 key areas of psychosocial functioning: QOL, mood, and perceived stress level. The results from this single prospective cohort study suggest that these areas of functioning improve after participating in wellness coaching; however, randomized clinical trials involving large samples of diverse individuals are needed to establish level 1 evidence for wellness coaching. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Sfontouris, Ioannis A; Martins, Wellington P; Nastri, Carolina O; Viana, Iara G R; Navarro, Paula A; Raine-Fenning, Nick; van der Poel, Sheryl; Rienzi, Laura; Racowsky, Catherine

2016-10-01

The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF. We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate. No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2  = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2  = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2  = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2  = 93 %). The overall quality of the evidence was very low for all these four outcomes. Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

Comparison of the benefits of cochlear implantation versus contra-lateral routing of signal hearing aids in adult patients with single-sided deafness: study protocol for a prospective within-subject longitudinal trial.

PubMed

Kitterick, Pádraig T; O'Donoghue, Gerard M; Edmondson-Jones, Mark; Marshall, Andrew; Jeffs, Ellen; Craddock, Louise; Riley, Alison; Green, Kevin; O'Driscoll, Martin; Jiang, Dan; Nunn, Terry; Saeed, Shakeel; Aleksy, Wanda; Seeber, Bernhard U

2014-01-01

Individuals with a unilateral severe-to-profound hearing loss, or single-sided deafness, report difficulty with listening in many everyday situations despite having access to well-preserved acoustic hearing in one ear. The standard of care for single-sided deafness available on the UK National Health Service is a contra-lateral routing of signals hearing aid which transfers sounds from the impaired ear to the non-impaired ear. This hearing aid has been found to improve speech understanding in noise when the signal-to-noise ratio is more favourable at the impaired ear than the non-impaired ear. However, the indiscriminate routing of signals to a single ear can have detrimental effects when interfering sounds are located on the side of the impaired ear. Recent published evidence has suggested that cochlear implantation in individuals with a single-sided deafness can restore access to the binaural cues which underpin the ability to localise sounds and segregate speech from other interfering sounds. The current trial was designed to assess the efficacy of cochlear implantation compared to a contra-lateral routing of signals hearing aid in restoring binaural hearing in adults with acquired single-sided deafness. Patients are assessed at baseline and after receiving a contra-lateral routing of signals hearing aid. A cochlear implant is then provided to those patients who do not receive sufficient benefit from the hearing aid. This within-subject longitudinal design reflects the expected care pathway should cochlear implantation be provided for single-sided deafness on the UK National Health Service. The primary endpoints are measures of binaural hearing at baseline, after provision of a contra-lateral routing of signals hearing aid, and after cochlear implantation. Binaural hearing is assessed in terms of the accuracy with which sounds are localised and speech is perceived in background noise. The trial is also designed to measure the impact of the interventions on hearing- and health-related quality of life. This multi-centre trial was designed to provide evidence for the efficacy of cochlear implantation compared to the contra-lateral routing of signals. A purpose-built sound presentation system and established measurement techniques will provide reliable and precise measures of binaural hearing. Current Controlled Trials http://www.controlled-trials.com/ISRCTN33301739 (05/JUL/2013).

Single-injection femoral nerve block. Effects on the independence level in functional activities in the early postoperative period in patients with total knee arthroplasty.

PubMed

Tugay, Nazan; Saricaoglu, Fatma; Satilmis, Tulin; Alpar, Ulku; Akarcali, Inci; Citaker, Seyit; Tugay, Umut; Atilla, Bulent; Tokgozoglu, Mazhar

2006-07-01

To investigate the efficacy of single injection femoral nerve block (FNB) on the independence level in functional activities in the early postoperative period in patients with total knee arthroplasty (TKA). We conducted this prospective, randomized, blinded trial in the Department of Orthopedics and Traumatology, Hacettepe University Hospital Ankara, Turkey, between June 2003 and April 2004. Twenty-three patients scheduled for elective TKA were randomly divided into 3 groups. Group I received preemptive single injection FNB, group II received postoperative single injection FNB, and group III served as a control group. Intravenous morphine patient controlled analgesia (PCA) was used following surgery in all groups. Morphine dose and pain score defined by the visual analog scale (VAS) were recorded postoperatively at the 15th minute, 30th minute, 1st, 4th, 6th, 12th, 24th, and 48th hours. A standard rehabilitation protocol was applied for all patients. The independence level in functional activities was assessed during the first 2 postoperative days and at discharge with the Iowa Level of Assistance Scale (ILAS) and the Iowa Ambulation Speed Scale (IASS). Physical therapists that enrolled in the study were blinded to the groups. Pain scores were significantly different between the groups (p<0.05). The preemptive and postoperative FNB group`s VAS scores were both significantly lower than the control group (p<0.05). However, there was no significant difference in VAS scores between preemptive and postoperative FNB groups (p>0.05). There was no statistically significant difference between the groups in any of the functional scores in the first 2 postoperative days, and at discharge (p>0.05). Single injection FNB provided effective analgesia in patients undergoing TKA. However, the independence level in functional activities in the early postoperative period was not influenced by the analgesia method.

Spatiotemporal analysis of single-trial EEG of emotional pictures based on independent component analysis and source location

NASA Astrophysics Data System (ADS)

Liu, Jiangang; Tian, Jie

2007-03-01

The present study combined the Independent Component Analysis (ICA) and low-resolution brain electromagnetic tomography (LORETA) algorithms to identify the spatial distribution and time course of single-trial EEG record differences between neural responses to emotional stimuli vs. the neutral. Single-trial multichannel (129-sensor) EEG records were collected from 21 healthy, right-handed subjects viewing the emotion emotional (pleasant/unpleasant) and neutral pictures selected from International Affective Picture System (IAPS). For each subject, the single-trial EEG records of each emotional pictures were concatenated with the neutral, and a three-step analysis was applied to each of them in the same way. First, the ICA was performed to decompose each concatenated single-trial EEG records into temporally independent and spatially fixed components, namely independent components (ICs). The IC associated with artifacts were isolated. Second, the clustering analysis classified, across subjects, the temporally and spatially similar ICs into the same clusters, in which nonparametric permutation test for Global Field Power (GFP) of IC projection scalp maps identified significantly different temporal segments of each emotional condition vs. neutral. Third, the brain regions accounted for those significant segments were localized spatially with LORETA analysis. In each cluster, a voxel-by-voxel randomization test identified significantly different brain regions between each emotional condition vs. the neutral. Compared to the neutral, both emotional pictures elicited activation in the visual, temporal, ventromedial and dorsomedial prefrontal cortex and anterior cingulated gyrus. In addition, the pleasant pictures activated the left middle prefrontal cortex and the posterior precuneus, while the unpleasant pictures activated the right orbitofrontal cortex, posterior cingulated gyrus and somatosensory region. Our results were well consistent with other functional imaging studies, while revealed temporal dynamics of emotional processing of specific brain structure with high temporal resolution.

Enhanced brainstem and cortical evoked response amplitudes: single-trial covariance analysis.

PubMed

Galbraith, G C

2001-06-01

The purpose of the present study was to develop analytic procedures that improve the definition of sensory evoked response components. Such procedures could benefit all recordings but would especially benefit difficult recordings where many trials are contaminated by muscle and movement artifacts. First, cross-correlation and latency adjustment analyses were applied to the human brainstem frequency-following response and cortical auditory evoked response recorded on the same trials. Lagged cross-correlation functions were computed, for each of 17 subjects, between single-trial data and templates consisting of the sinusoid stimulus waveform for the brainstem response and the subject's own smoothed averaged evoked response P2 component for the cortical response. Trials were considered in the analysis only if the maximum correlation-squared (r2) exceeded .5 (negatively correlated trials were thus included). Identical correlation coefficients may be based on signals with quite different amplitudes, but it is possible to assess amplitude by the nonnormalized covariance function. Next, an algorithm is applied in which each trial with negative covariance is matched to a trial with similar, but positive, covariance and these matched-trial pairs are deleted. When an evoked response signal is present in the data, the majority of trials positively correlate with the template. Thus, a residual of positively correlated trials remains after matched covariance trials are deleted. When these residual trials are averaged, the resulting brainstem and cortical responses show greatly enhanced amplitudes. This result supports the utility of this analysis technique in clarifying and assessing evoked response signals.

Intelligent single switch wheelchair navigation.

PubMed

Ka, Hyun W; Simpson, Richard; Chung, Younghyun

2012-11-01

We have developed an intelligent single switch scanning interface and wheelchair navigation assistance system, called intelligent single switch wheelchair navigation (ISSWN), to improve driving safety, comfort and efficiency for individuals who rely on single switch scanning as a control method. ISSWN combines a standard powered wheelchair with a laser rangefinder, a single switch scanning interface and a computer. It provides the user with context sensitive and task specific scanning options that reduce driving effort based on an interpretation of sensor data together with user input. Trials performed by 9 able-bodied participants showed that the system significantly improved driving safety and efficiency in a navigation task by significantly reducing the number of switch presses to 43.5% of traditional single switch wheelchair navigation (p < 0.001). All participants made a significant improvement (39.1%; p < 0.001) in completion time after only two trials.

Intertrial Temporal Contextual Cuing: Association across Successive Visual Search Trials Guides Spatial Attention

ERIC Educational Resources Information Center

Ono, Fuminori; Jiang, Yuhong; Kawahara, Jun-ichiro

2005-01-01

Contextual cuing refers to the facilitation of performance in visual search due to the repetition of the same displays. Whereas previous studies have focused on contextual cuing within single-search trials, this study tested whether 1 trial facilitates visual search of the next trial. Participants searched for a T among Ls. In the training phase,…

Classifying four-category visual objects using multiple ERP components in single-trial ERP.

PubMed

Qin, Yu; Zhan, Yu; Wang, Changming; Zhang, Jiacai; Yao, Li; Guo, Xiaojuan; Wu, Xia; Hu, Bin

2016-08-01

Object categorization using single-trial electroencephalography (EEG) data measured while participants view images has been studied intensively. In previous studies, multiple event-related potential (ERP) components (e.g., P1, N1, P2, and P3) were used to improve the performance of object categorization of visual stimuli. In this study, we introduce a novel method that uses multiple-kernel support vector machine to fuse multiple ERP component features. We investigate whether fusing the potential complementary information of different ERP components (e.g., P1, N1, P2a, and P2b) can improve the performance of four-category visual object classification in single-trial EEGs. We also compare the classification accuracy of different ERP component fusion methods. Our experimental results indicate that the classification accuracy increases through multiple ERP fusion. Additional comparative analyses indicate that the multiple-kernel fusion method can achieve a mean classification accuracy higher than 72 %, which is substantially better than that achieved with any single ERP component feature (55.07 % for the best single ERP component, N1). We compare the classification results with those of other fusion methods and determine that the accuracy of the multiple-kernel fusion method is 5.47, 4.06, and 16.90 % higher than those of feature concatenation, feature extraction, and decision fusion, respectively. Our study shows that our multiple-kernel fusion method outperforms other fusion methods and thus provides a means to improve the classification performance of single-trial ERPs in brain-computer interface research.

The patient general satisfaction of mandibular single-implant overdentures and conventional complete dentures: Study protocol for a randomized crossover trial.

PubMed

Kanazawa, Manabu; Tanoue, Mariko; Miyayasu, Anna; Takeshita, Shin; Sato, Daisuke; Asami, Mari; Lam, Thuy Vo; Thu, Khaing Myat; Oda, Ken; Komagamine, Yuriko; Minakuchi, Shunsuke; Feine, Jocelyne

2018-05-01

Mandibular overdentures retained by a single implant placed in the midline of edentulous mandible have been reported to be more comfortable and function better than complete dentures. Although single-implant overdentures are still more costly than conventional complete dentures, there are a few studies which investigated whether mandibular single-implant overdentures are superior to complete dentures when patient general satisfaction is compared. The aim of this study is to assess patient general satisfaction with mandibular single-implant overdentures and complete dentures. This study is a randomized crossover trial to compare mandibular single-implant overdentures and complete dentures in edentulous individuals. Participant recruitment is ongoing at the time of this submission. Twenty-two participants will be recruited. New mandibular complete dentures will be fabricated. A single implant will be placed in the midline of the edentulous mandible. The mucosal surface of the complete denture around the implant will be relieved for 3 months. The participants will then be randomly allocated into 2 groups according to the order of the interventions; group 1 will receive single-implant overdentures first and will wear them for 2 months, followed by complete dentures for 2 months. Group 2 will receive the same treatments in a reverse order. After experiencing the 2 interventions, the participants will choose one of the mandibular prostheses, and yearly follow-up visits are planned for 5 years. The primary outcome of this trial is patient ratings of general satisfaction on 100 mm visual analog scales. Assessments of the prostheses and oral health-related quality of life will also be recorded as patient-reported outcomes. The secondary outcomes are cost and time for treatment. Masticatory efficiency and cognitive capacity will also be recorded. Furthermore, qualitative research will be performed to investigate the factors associated with success of these mandibular denture types. Clinical outcomes, such as implant survival rate, marginal bone loss, and prosthodontic complications, will also be recorded. The results of this randomized crossover trial will clarify whether mandibular single implants and overdentures for edentulous individuals provide better patient general satisfaction when compared to conventional complete dentures. This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center (UMIN000017883).

Feasibility of the Atlas Unicompartmental Knee System Load Absorber in Improving Pain Relief and Function in Patients Needing Unloading of the Medial Compartment of the Knee: 1-Year Follow-Up of a Prospective, Multicenter, Single-Arm Pilot Study (PHANTOM High Flex Trial).

PubMed

Slynarski, Konrad; Walawski, Jacek; Smigielski, Robert; van der Merwe, Willem

2017-01-01

In young patients with medial knee osteoarthritis (OA), surgical intervention may not be desirable due to preferences to avoid bone cutting procedures, return to high activity levels, and prolong implant survival. The Atlas Knee System was designed to fill the gap between ineffective conservative treatments and invasive surgery. This single-arm study included 26 patients, aged 25 to 65 years, who completed 12 months of follow-up. All dimensions of the Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Society Score significantly improved from baseline to 12 months. About 96.2% and 92.3% of patients experienced a ⩾20% improvement in their KOOS pain and WOMAC pain scores, respectively, at 12 months. This study highlights the potential benefit of a joint unloading device in the management of young patients with medial knee OA. The trial is still ongoing and another analysis is planned at 24 months.

Rapid, generalized adaptation to asynchronous audiovisual speech

PubMed Central

Van der Burg, Erik; Goodbourn, Patrick T.

2015-01-01

The brain is adaptive. The speed of propagation through air, and of low-level sensory processing, differs markedly between auditory and visual stimuli; yet the brain can adapt to compensate for the resulting cross-modal delays. Studies investigating temporal recalibration to audiovisual speech have used prolonged adaptation procedures, suggesting that adaptation is sluggish. Here, we show that adaptation to asynchronous audiovisual speech occurs rapidly. Participants viewed a brief clip of an actor pronouncing a single syllable. The voice was either advanced or delayed relative to the corresponding lip movements, and participants were asked to make a synchrony judgement. Although we did not use an explicit adaptation procedure, we demonstrate rapid recalibration based on a single audiovisual event. We find that the point of subjective simultaneity on each trial is highly contingent upon the modality order of the preceding trial. We find compelling evidence that rapid recalibration generalizes across different stimuli, and different actors. Finally, we demonstrate that rapid recalibration occurs even when auditory and visual events clearly belong to different actors. These results suggest that rapid temporal recalibration to audiovisual speech is primarily mediated by basic temporal factors, rather than higher-order factors such as perceived simultaneity and source identity. PMID:25716790

Convolutional neural networks for event-related potential detection: impact of the architecture.

PubMed

Cecotti, H

2017-07-01

The detection of brain responses at the single-trial level in the electroencephalogram (EEG) such as event-related potentials (ERPs) is a difficult problem that requires different processing steps to extract relevant discriminant features. While most of the signal and classification techniques for the detection of brain responses are based on linear algebra, different pattern recognition techniques such as convolutional neural network (CNN), as a type of deep learning technique, have shown some interests as they are able to process the signal after limited pre-processing. In this study, we propose to investigate the performance of CNNs in relation of their architecture and in relation to how they are evaluated: a single system for each subject, or a system for all the subjects. More particularly, we want to address the change of performance that can be observed between specifying a neural network to a subject, or by considering a neural network for a group of subjects, taking advantage of a larger number of trials from different subjects. The results support the conclusion that a convolutional neural network trained on different subjects can lead to an AUC above 0.9 by using an appropriate architecture using spatial filtering and shift invariant layers.

Genetic associations between fibrinogen and cognitive performance in three Scottish cohorts.

PubMed

Marioni, Riccardo E; Deary, Ian J; Murray, Gordon D; Lowe, Gordon D O; Strachan, Mark W J; Luciano, Michelle; Houlihan, Lorna M; Gow, Alan J; Harris, Sarah E; Rumley, Ann; Stewart, Marlene C; Fowkes, F Gerry R; Price, Jackie F

2011-09-01

There is increasing evidence to suggest that elevated plasma levels of fibrinogen are associated with late-life cognitive performance. This study tested the association of single nucleotide polymorphisms in the fibrinogen α (FGA) and β (FGB) genes with cognitive performance. Data were analysed from three community-dwelling populations of older persons (>50 years) in central Scotland: the Aspirin for Asymptomatic Atherosclerosis (AAA) Trial (n = 2,091), the Edinburgh Type 2 Diabetes Study (ET2DS, n = 1,066), and the Lothian Birth Cohort 1936 (LBC1936, n = 1,091). Cognition was assessed using a battery of five, seven, and four psychometric tests, respectively. This information was used to derive a general cognitive factor. Weakly significant associations were found between the rs4220 (FGB), and rs2227412 (FGB) SNPs and a single test of cognitive performance in the AAA Trial (p < 0.05). These findings did not replicate in the LBC1936 or ET2DS cohorts, except for the rs2227412 SNP, which was significantly associated with the general cognitive factor in the ET2DS (p = 3.3 × 10(-4)). A summary term that combined results from all three studies suggested that the rs2227412 genotype associated with reduced cognitive ability also associated with higher plasma fibrinogen levels. These findings suggest a tentative role for fibrinogen as a determinant of late-life cognitive performance and justify further attempts at replication in older persons.

A single aerobic exercise session accelerates movement execution but not central processing.

PubMed

Beyer, Kit B; Sage, Michael D; Staines, W Richard; Middleton, Laura E; McIlroy, William E

2017-03-27

Previous research has demonstrated that aerobic exercise has disparate effects on speed of processing and movement execution. In simple and choice reaction tasks, aerobic exercise appears to increase speed of movement execution while speed of processing is unaffected. In the flanker task, aerobic exercise has been shown to reduce response time on incongruent trials more than congruent trials, purportedly reflecting a selective influence on speed of processing related to cognitive control. However, it is unclear how changes in speed of processing and movement execution contribute to these exercise-induced changes in response time during the flanker task. This study examined how a single session of aerobic exercise influences speed of processing and movement execution during a flanker task using electromyography to partition response time into reaction time and movement time, respectively. Movement time decreased during aerobic exercise regardless of flanker congruence but returned to pre-exercise levels immediately after exercise. Reaction time during incongruent flanker trials decreased over time in both an aerobic exercise and non-exercise control condition indicating it was not specifically influenced by exercise. This disparate influence of aerobic exercise on movement time and reaction time indicates the importance of partitioning response time when examining the influence of aerobic exercise on speed of processing. The decrease in reaction time over time independent of aerobic exercise indicates that interpreting pre-to-post exercise changes in behavior requires caution. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

The NUTRAOLEOUM Study, a randomized controlled trial, for achieving nutritional added value for olive oils.

PubMed

Biel, Sara; Mesa, Maria-Dolores; de la Torre, Rafael; Espejo, Juan-Antonio; Fernández-Navarro, Jose-Ramón; Fitó, Montserrat; Sánchez-Rodriguez, Estefanía; Rosa, Carmen; Marchal, Rosa; Alche, Juan de Dios; Expósito, Manuela; Brenes, Manuel; Gandul, Beatriz; Calleja, Miguel Angel; Covas, María-Isabel

2016-10-22

Virgin olive oil, a recognized healthy food, cannot be consumed in great quantities. We aim to assess in humans whether an optimized virgin olive oil with high phenolic content (OVOO, 429 mg/Kg) and a functional one (FOO), both rich in phenolic compounds (429 mg/Kg) and triterpenic acids (389 mg/kg), could provide health benefits additional to those supplied a by a standard virgin olive oil (VOO). A randomized, double-blind, crossover, controlled study will be conducted. Healthy volunteers (aged 20 to 50) will be randomized into one of three groups of daily raw olive oil consumption: VOO, OVOO, and FOO (30 mL/d). Olive oils will be administered over 3-week periods preceded by 2-week washout ones. The main outcomes will be markers of lipid and DNA oxidation, inflammation, and vascular damage. A bioavailability and dose-response study will be nested within this sustained- consumption one. It will be made up of 18 volunteers and be performed at two stages after a single dose of each olive oil. Endothelial function and nitric oxide will be assessed at baseline and at 4 h and 6 h after olive oil single dose ingestion. For the first time the NUTRAOLEUM Study will provide first level evidence on the health benefits in vivo in humans of olive oil triterpenes (oleanolic and maslinic acid) in addition to their bioavailability and disposition. The Trial has been registered in ClinicalTrials.gov ID: NCT02520739 .

A Single Bout of Aerobic Exercise Reduces Anxiety Sensitivity But Not Intolerance of Uncertainty or Distress Tolerance: A Randomized Controlled Trial.

PubMed

LeBouthillier, Daniel M; Asmundson, Gordon J G

2015-01-01

Several mechanisms have been posited for the anxiolytic effects of exercise, including reductions in anxiety sensitivity through interoceptive exposure. Studies on aerobic exercise lend support to this hypothesis; however, research investigating aerobic exercise in comparison to placebo, the dose-response relationship between aerobic exercise anxiety sensitivity, the efficacy of aerobic exercise on the spectrum of anxiety sensitivity and the effect of aerobic exercise on other related constructs (e.g. intolerance of uncertainty, distress tolerance) is lacking. We explored reductions in anxiety sensitivity and related constructs following a single session of exercise in a community sample using a randomized controlled trial design. Forty-one participants completed 30 min of aerobic exercise or a placebo stretching control. Anxiety sensitivity, intolerance of uncertainty and distress tolerance were measured at baseline, post-intervention and 3-day and 7-day follow-ups. Individuals in the aerobic exercise group, but not the control group, experienced significant reductions with moderate effect sizes in all dimensions of anxiety sensitivity. Intolerance of uncertainty and distress tolerance remained unchanged in both groups. Our trial supports the efficacy of aerobic exercise in uniquely reducing anxiety sensitivity in individuals with varying levels of the trait and highlights the importance of empirically validating the use of aerobic exercise to address specific mental health vulnerabilities. Aerobic exercise may have potential as a temporary substitute for psychotherapy aimed at reducing anxiety-related psychopathology.

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

PubMed

Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

2016-06-01

A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). © Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

Clinical trials in dentistry in India: Analysis from trial registry.

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy participants. From 2011, some of the postgraduate thesis trials had also been registered (2011-8; 2012-8; 2013-13; 2014-6). Inadequacy in reporting the method of randomization and allocation concealment was observed in 37/67 (55.2%) and 31/67 (46.2%) clinical trials respectively. A considerable number of postgraduate theses was also registered with CTRI in dentistry and majority of the clinical trials despite being completed are not yet published. The number of clinical trials in dentistry are low in India, and more focus should be placed by dental investigators regarding the reporting standards. Furthermore, researchers and trial sponsors should aim at publication of the research findings so that it is made publically available for use. A clear-cut need exists for an increase in both the quantity and quality of clinical trials in dentistry.

Effect of hand and foot surface stroke massage on anxiety and vital signs in patients with acute coronary syndrome: A randomized clinical trial.

PubMed

Alimohammad, Hasheminia Seyyed; Ghasemi, Zahra; Shahriar, Salehi; Morteza, Sedehi; Arsalan, Khaledifar

2018-05-01

Anxiety affects various body systems, which leads to an increase in respiratory rate, heart rate, blood pressure, and myocardial oxygen demand. The aim of this study was to investigate the effect of hand and foot surface stroke massage on the level of anxiety and vital signs in patients with acute coronary syndrome (ACS). The single-blind clinical trial was performed on 70 patients with ACS. The patients were randomly assigned to the case and control groups. Anxiety levels were controlled 30 min before and 15 min after the intervention. The vital signs were checked in the two groups before, immediately after, 60 min, and 90 min after the intervention. The data were analyzed using SPSS software, descriptive statistics (mean ± standard deviation), independent t-test, paired t-test, and chi-square test. No significant difference was observed in the patients' levels of anxiety, systolic blood pressure, diastolic blood pressure, respiratory rate, and pulse rate before the intervention. However, after the intervention, the mean changes in the levels of anxiety, blood pressure, heart rate, and respiratory rate were significant. Hand and foot massage can be a useful nursing intervention in attenuating anxiety levels and improving the vital signs in patients. Copyright © 2018. Published by Elsevier Ltd.

Immunotherapy for cow's milk allergy

PubMed Central

Takahashi, Masaya; Soejima, Kazukiko; Hatano, Yasuko; Minami, Hirotaka

2017-01-01

ABSTRACT Oral immunotherapy (OIT) is used regularly for young children with cow's milk (CM) allergy and has been shown to be effective in several studies. However, adverse events occur frequently during OIT. Furthermore, there are only 5 randomized controlled trial studies of CM-OIT and these are low-powered single center trials. Therefore, evidence levels are also low and sometimes frequent and severe allergic events occur during the OIT. Furthermore, there are no standardized protocols in pediatric allergy guidelines from several countries and studies with long-term follow-up observations and clinical tolerance defined as sustained unresponsiveness are rare. Additionally, clinical tolerance by OIT is generally not well defined and obscure. Thus, several problems remain to be resolved, however we hope OIT in combination with omalizumab and less allergenic heated CM products will resolve these problems in the future. PMID:28825866

A randomised controlled trial of multiple periods of outdoor free-play to increase moderate-to-vigorous physical activity among 3 to 6 year old children attending childcare: study protocol.

PubMed

Wolfenden, Luke; Wiggers, John; Morgan, Philip; Razak, Lubna Abdul; Jones, Jannah; Finch, Meghan; Sutherland, Rachel; Lecathelinais, Christophe; Gillham, Karen; Yoong, Sze Lin

2016-09-02

The implementation of physical activity interventions in centre-based childcare services has been recommended to improve child health. This study aims to evaluate the efficacy of scheduling multiple periods of outdoor free play in increasing the time children spend in moderate-to-vigorous physical activity (MVPA) during childcare. The study will employ a between group cluster randomised controlled trial design. Fourteen childcare services in the Hunter New England region of New South Wales, Australia, who currently implement a single session of free outdoor play between their core operational hours of 9 am to 3 pm will be recruited into the trial. Childcare services will be randomised to an intervention or a no intervention control group. Childcare services in the intervention group will be supported by an early childhood education specialist to provide three periods of outdoor free play for children between the hours of 9 am to 3 pm. Each period of outdoor free play will be at least 15 min in duration but must equate to their total usual duration of outdoor play. Services in the control group will continue to implement a single period of outdoor play. The primary trial outcome is minutes of time children spend in MVPA whilst in care assessed objectively via accelerometer over 5 days. Outcome assessment will occur at baseline and 3 months post baseline. Generalised Linear Mixed Models (GLMM) under an intention to treat framework will be used to compare differences between groups in the primary trial outcome at follow-up. Sensitivity analysis will be conducted to test assumptions of missing data. Per protocol analysis will be performed using services that implemented the intervention as intended and subgroup analysis undertaken by gender and baseline physical activity levels of children. The study tests a simple ecological intervention that has the potential to increase child physical activity in care. Australian New Zealand Clinical Trials Registry 12616000347460 . Prospectively registered 17th March 2016.

An open cluster-randomized, 18-month trial to compare the effectiveness of educational outreach visits with usual guideline dissemination to improve family physician prescribing

PubMed Central

2014-01-01

Background The Portuguese National Health Directorate has issued clinical practice guidelines on prescription of anti-inflammatory drugs, acid suppressive therapy, and antiplatelets. However, their effectiveness in changing actual practice is unknown. Methods The study will compare the effectiveness of educational outreach visits regarding the improvement of compliance with clinical guidelines in primary care against usual dissemination strategies. A cost-benefit analysis will also be conducted. We will carry out a parallel, open, superiority, randomized trial directed to primary care physicians. Physicians will be recruited and allocated at a cluster-level (primary care unit) by minimization. Data will be analyzed at the physician level. Primary care units will be eligible if they use electronic prescribing and have at least four physicians willing to participate. Physicians in intervention units will be offered individual educational outreach visits (one for each guideline) at their workplace during a six-month period. Physicians in the control group will be offered a single unrelated group training session. Primary outcomes will be the proportion of cyclooxygenase-2 inhibitors prescribed in the anti-inflammatory class, and the proportion of omeprazole in the proton pump inhibitors class at 18 months post-intervention. Prescription data will be collected from the regional pharmacy claims database. We estimated a sample size of 110 physicians in each group, corresponding to 19 clusters with a mean size of 6 physicians. Outcome collection and data analysis will be blinded to allocation, but due to the nature of the intervention, physicians and detailers cannot be blinded. Discussion This trial will attempt to address unresolved issues in the literature, namely, long term persistence of effect, the importance of sequential visits in an outreach program, and cost issues. If successful, this trial may be the cornerstone for deploying large scale educational outreach programs within the Portuguese National Health Service. Trial registration ClinicalTrials.gov number NCT01984034. PMID:24423370

Comparison of outcome measures and complication rates following three different approaches for primary total hip arthroplasty: a pragmatic randomised controlled trial.

PubMed

Talia, Adrian J; Coetzee, Cassandra; Tirosh, Oren; Tran, Phong

2018-01-08

Total hip arthroplasty is one of the most commonly performed surgical procedures worldwide. There are a number of surgical approaches for total hip arthroplasty and no high-level evidence supporting one approach over the other. Each approach has its unique benefits and drawbacks. This trial aims to directly compare the three most common surgical approaches for total hip arthroplasty. This is a single-centre study conducted at Western Health, Melbourne, Australia; a large metropolitan centre. It is a pragmatic, parallel three-arm, randomised controlled trial. Sample size will be 243 participants (81 in each group). Randomisation will be secure, web-based and managed by an independent statistician. Patients and research team will be blinded pre-operatively, but not post-operatively. Intervention will be either direct anterior, lateral or posterior approach for total hip arthroplasty, and the three arms will be directly compared. Participants will be aged over 18 years, able to provide informed consent and recruited from our outpatients. Patients who are having revision surgery or have indications for hip replacement other than osteoarthritis (i.e., fracture, malignancy, development dysplasia) will be excluded from the trial. The Oxford Hip Score will be determined for patients pre-operatively and 6 weeks, 6, 12 and 24 months post-operatively. The Oxford Hip Score at 24 months will be the primary outcome measure. Secondary outcome measures will be dislocation, infection, intraoperative and peri-prosthetic fracture rate, length of hospital stay and pain level, reported using a visual analogue scale. Many studies have evaluated approaches for total hip arthroplasty and arthroplasty registries worldwide are now collecting this data. However no study to date has compared these three common approaches directly in a randomised fashion. No trial has used patient-reported outcome measures to evaluate success. This pragmatic study aims to identify differences in patient perception of total hip arthroplasty depending on surgical approach. Australian New Zealand Clinical Trials Registry, ACTRN12617000272392 . Registered on 22 February 2017.

Can genetic-based advice help you lose weight? Findings from the Food4Me European randomized controlled trial.

PubMed

Celis-Morales, Carlos; Marsaux, Cyril Fm; Livingstone, Katherine M; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; Fallaize, Rosalind; Macready, Anna L; O'Donovan, Clare; Woolhead, Clara; Forster, Hannah; Kolossa, Silvia; Daniel, Hannelore; Moschonis, George; Mavrogianni, Christina; Manios, Yannis; Surwillo, Agnieszka; Traczyk, Iwona; Drevon, Christian A; Grimaldi, Keith; Bouwman, Jildau; Gibney, Mike J; Walsh, Marianne C; Gibney, Eileen R; Brennan, Lorraine; Lovegrove, Julie A; Martinez, J Alfredo; Saris, Wim Hm; Mathers, John C

2017-05-01

Background: There has been limited evidence about whether genotype-tailored advice provides extra benefits in reducing obesity-related traits compared with the benefits of conventional one-size-fits-all advice. Objective: We determined whether the disclosure of information on fat-mass and obesity-associated ( FTO ) genotype risk had a greater effect on a reduction of obesity-related traits in risk carriers than in nonrisk carriers across different levels of personalized nutrition. Design: A total of 683 participants (women: 51%; age range: 18-73 y) from the Food4Me randomized controlled trial were included in this analysis. Participants were randomly assigned to 4 intervention arms as follows: level 0, control group; level 1, dietary group; level 2, phenotype group; and level 3, genetic group. FTO (single nucleotide polymorphism rs9939609) was genotyped at baseline in all participants, but only subjects who were randomly assigned to level 3 were informed about their genotypes. Level 3 participants were stratified into risk carriers (AA/AT) and nonrisk carriers (TT) of the FTO gene for analyses. Height, weight, and waist circumference (WC) were self-measured and reported at baseline and months 3 and 6. Results: Changes in adiposity markers were greater in participants who were informed that they carried the FTO risk allele (level 3 AT/AA carriers) than in the nonpersonalized group (level 0) but not in the other personalized groups (level 1 and 2). Mean reductions in weight and WC at month 6 were greater for FTO risk carriers than for noncarriers in the level 3 group [-2.28 kg (95% CI: -3.06, -1.48 kg) compared with -1.99 kg (-2.19, -0.19 kg), respectively ( P = 0.037); and -4.34 cm (-5.63, -3.08 cm) compared with -1.99 cm (-4.04, -0.05 cm), respectively, ( P = 0.048)]. Conclusions: There are greater body weight and WC reductions in risk carriers than in nonrisk carriers of the FTO gene. This trial was registered at clinicaltrials.gov as NCT01530139. © 2017 American Society for Nutrition.

Single Trial EEG Patterns for the Prediction of Individual Differences in Fluid Intelligence.

PubMed

Qazi, Emad-Ul-Haq; Hussain, Muhammad; Aboalsamh, Hatim; Malik, Aamir Saeed; Amin, Hafeez Ullah; Bamatraf, Saeed

2016-01-01

Assessing a person's intelligence level is required in many situations, such as career counseling and clinical applications. EEG evoked potentials in oddball task and fluid intelligence score are correlated because both reflect the cognitive processing and attention. A system for prediction of an individual's fluid intelligence level using single trial Electroencephalography (EEG) signals has been proposed. For this purpose, we employed 2D and 3D contents and 34 subjects each for 2D and 3D, which were divided into low-ability (LA) and high-ability (HA) groups using Raven's Advanced Progressive Matrices (RAPM) test. Using visual oddball cognitive task, neural activity of each group was measured and analyzed over three midline electrodes (Fz, Cz, and Pz). To predict whether an individual belongs to LA or HA group, features were extracted using wavelet decomposition of EEG signals recorded in visual oddball task and support vector machine (SVM) was used as a classifier. Two different types of Haar wavelet transform based features have been extracted from the band (0.3 to 30 Hz) of EEG signals. Statistical wavelet features and wavelet coefficient features from the frequency bands 0.0-1.875 Hz (delta low) and 1.875-3.75 Hz (delta high), resulted in the 100 and 98% prediction accuracies, respectively, both for 2D and 3D contents. The analysis of these frequency bands showed clear difference between LA and HA groups. Further, discriminative values of the features have been validated using statistical significance tests and inter-class and intra-class variation analysis. Also, statistical test showed that there was no effect of 2D and 3D content on the assessment of fluid intelligence level. Comparisons with state-of-the-art techniques showed the superiority of the proposed system.

Managing Injuries of the Neck Trial (MINT): a randomised controlled trial of treatments for whiplash injuries.

PubMed

Lamb, S E; Williams, M A; Williamson, E M; Gates, S; Withers, E J; Mt-Isa, S; Ashby, D; Castelnuovo, E; Underwood, M; Cooke, M W

2012-01-01

To examine the clinical effectiveness of a stepped care approach over a 12-month period after an acute whiplash injury; to estimate the costs and cost-effectiveness of each strategy including treatments and subsequent health-care costs; and to gain participants' perspective on experiencing whiplash injury, NHS treatment, and recovery within the context of the Managing Injuries of the Neck Trial (MINT). Two linked, pragmatic, randomised controlled trials. In Step 1, emergency departments (EDs) were cluster randomised to usual care advice (UCA) or The Whiplash Book advice (WBA)/active management advice. In Step 2, participants were individually randomised to either a single session of advice from a physiotherapist or a physiotherapy package of up to six sessions. An economic evaluation and qualitative study were run in parallel with the trial. Twelve NHS trusts in England comprising 15 EDs. People who attended EDs with an acute whiplash injury of whiplash-associated disorder grades I-III were eligible for Step 1. People who had attended EDs with whiplash injuries and had persistent symptoms 3 weeks after ED attendance were eligible for Step 2. In Step 1, the control intervention was UCA and the experimental intervention was a psycho-educational intervention (WBA/active management advice). In Step 2 the control treatment was reinforcement of the advice provided in Step 1 and the experimental intervention was a package of up to six physiotherapy treatments. The primary outcome was the Neck Disability Index (NDI), which measures severity and frequency of pain and symptoms, and a range of activities including self-care, driving, reading, sleeping and recreation. Secondary outcomes included the mental and physical health-related quality-of-life (HRQoL) subscales of the Short Form questionnaire-12 items (SF-12) and the number of work days lost. A total of 3851 patients were recruited to Step 1 of the trial. 1598 patients attending EDs were randomised to UCA, and 2253 were randomised to WBA/active management. Outcome data were obtained at 12 months for 70% and 80% of participants at Step 1 and Step 2, respectively. The majority of people recovered from the injury. Eighteen per cent of the Step 1 cohort had late whiplash syndrome. There was no statistically or clinically significant difference observed in any of the outcomes for participants attending EDs randomised to UCA or active management advice [difference in NDI 0.5, 95% confidence interval (CI) -1.8 to 2.8]. In Step 2 the physiotherapy package resulted in improvements in neck disability at 4 months compared with a single advice session, but these effects were small at the population level (difference in NDI -3.2, 95% CI -5.8 to -0.7). The physiotherapy package was accompanied by a significant reduction in the number of work days lost at 4-month follow-up (difference -40.2, 95% CI -44.3 to -35.8). MINT suggests that enhanced psycho-educational interventions in EDs are no more effective than UCA in reducing the burden of acute whiplash injuries. A physiotherapy package provided to people who have persisting symptoms within the first 6 weeks of injury produced additional short-term benefits in neck disability compared with a single physiotherapy advice session. However, from a health-care perspective, the physiotherapy package was not cost-effective at current levels of willingness to pay. Both experimental treatments were associated with increased cost with no discernible gain in health-related quality of life. However, an important benefit of the physiotherapy package was a reduction in work days lost; consequently, the intervention may prove cost-effective at the societal level. Current Controlled Trials ISRCTN33302125. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 49. See the HTA programme website for further project information.

Protocol for a single-centre randomised controlled trial of multimodal periarticular anaesthetic infiltration versus single-agent femoral nerve blockade as analgesia for total knee arthroplasty: Perioperative Analgesia for Knee Arthroplasty (PAKA)

PubMed Central

Wall, P D H; Sprowson, A P; Parsons, N; Parsons, H; Achten, J; Balasubramanian, S; Costa, M L

2015-01-01

Introduction Total knee arthroplasty (TKA) surgery causes postoperative pain. The use of perioperative injections around the knee containing local anaesthetic, opiates and non-steroidal anti-inflammatory drugs has increased in popularity to manage pain. Theoretical advantages include reduced requirements for analgesia and earlier mobilisation. We propose a single-centre randomised controlled trial of multimodal periarticular anaesthetic infiltration versus femoral nerve anaesthetic blockade as analgesia for TKA. The aim is to determine, in patients undergoing TKA, if there is a difference in patient-reported pain scores on the visual analogue scale (VAS) prior to physiotherapy on day 1 postoperatively between treatment groups. Methods and analysis Patients undergoing a primary unilateral TKA at University Hospitals Coventry and Warwickshire Hospitals will be assessed for eligibility. A total of 264 patients will provide 90% power to detect a difference of 12 mm on the VAS on day 1 postoperatively at the 5% level. The trial will use 1:1 randomisation, stratified by mode of anaesthetic. Primary outcome measure will be the VAS for pain prior to physiotherapy on day 1. Secondary outcome measures include VAS on day 2, total use of opiate analgesia up to 48 h, ordinal pain scores up to 40 min after surgery, independent functional knee physiotherapist assessment on days 1 and 2. Oxford knee Scores (OKS), EuroQol (EQ-5D) and Douleur Neuropathic Pain Scores (DN2) will be recorded at baseline, 6 weeks and 12 months. Adverse events will be recorded up to 12 months. Analysis will investigate differences in VAS on day 1 between the two treatment groups on an intention-to-treat basis. Tests will be two-sided and considered to provide evidence for a significant difference if p values are less than 0.05. Ethics and dissemination NRES Committee West Midlands, 23 September 2013 (ref: 13/WM/0316). The results will be disseminated via peer-reviewed publications and conference presentations. Trial registration numbers ISRCTN 60611146 and EUDRACT Number 2013-002439-10 (protocol code number PAKA-33601-AS117013); Pre-results. PMID:26692559

75 FR 4827 - Submission for OMB Review; Comment Request Clinical Trials Reporting Program (CTRP) Database (NCI)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

...; Comment Request Clinical Trials Reporting Program (CTRP) Database (NCI) Summary: Under the provisions of... Collection: Title: Clinical Trials Reporting Program (CTRP) Database. Type of Information Collection Request... Program (CTRP) Database, to serve as a single, definitive source of information about all NCI-supported...

Trial Sequential Methods for Meta-Analysis

ERIC Educational Resources Information Center

Kulinskaya, Elena; Wood, John

2014-01-01

Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

Safety of primaquine given to people with G6PD deficiency: systematic review of prospective studies.

PubMed

Uthman, Olalekan A; Graves, Patricia M; Saunders, Rachel; Gelband, Hellen; Richardson, Marty; Garner, Paul

2017-08-22

Haemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people. Major electronic databases (to August 2016) were searched for single or short course 8-aminoquinolines (8-AQ) in (1) randomized comparisons against placebo in G6PD deficient people; and (2) observational comparisons in G6PD deficient compared to replete people. Two authors independently assessed eligibility, risk-of-bias, and extracted data. Five randomized controlled trials and four controlled observational cohorts were included. In G6PD deficient individuals, high-dose (0.75 mg/kg) PQ resulted in lower average haemoglobin levels at 7 days (mean difference [MD] -1.45 g/dl, 95% CI -2.17 to -0.74, 2 trials) and larger percentage fall from baseline to day 7 (MD -10.31%, 95% CI -17.69 to -2.92, 3 trials) compared to placebo. In G6PD deficient compared to replete people, average haemoglobin was lower at 7 days (MD -1.19 g/dl, 95% CI -1.94 to -0.44, 2 trials) and haemoglobin change from baseline to day 7 was greater (MD -9.10%, 95% CI -12.55 to -5.65, 5 trials). One small trial evaluated mid-range PQ dose (0.4-0.5 mg/kg) in G6PD deficient people, with no difference detected in average haemoglobin at day 7 compared to placebo. In one cohort comparing G6PD deficient and replete people there was a greater fall with G6PD deficiency (MD -4.99%, 95% CI -9.96 to -0.02). For low-dose PQ (0.1-0.25 mg/kg) in G6PD deficient people, haemoglobin change from baseline was similar to the placebo group (MD 1.72%, 95% CI -1.89 to 5.34, 2 trials). Comparing low dose PQ in G6PD deficient with replete people, the average haemoglobin was lower in the G6PD deficient group at 7 days (-0.57 g (95% CI -0.97 to -0.17, 1 trial)); although change from baseline was similar (MD -1.45%, 95% CI -5.69 to 2.78, 3 trials). Falls in average haemoglobin are less marked with the 0.1 to 0.25 mg/kg PQ than with the 0.75 mg/kg dose, and severe haemolytic events are not common. However, data were limited and the evidence GRADE was low or very low certainty.

Does 360° lumbar spinal fusion improve long-term clinical outcomes after failure of conservative treatment in patients with functionally disabling single-level degenerative lumbar disc disease? Results of 5-year follow-up in 75 postoperative patients.

PubMed

Zigler, Jack E; Delamarter, Rick B

2013-01-01

Surgical treatment of patients with mechanical degenerative disc disease has been controversial, but improvements in clinical outcomes have been shown in properly selected patients with disease-specific diagnoses, with fusion arguably now becoming the "gold standard" for surgical management of these patients. No published study thus far has been designed for prospective enrollment of patients with specific inclusion/exclusion criteria in whom at least 6 months of conservative therapy has failed and who are then offered a standardized surgical procedure and are followed up for 5 years. The study group was composed of the patients in the prospective, randomized Food and Drug Administration Investigational Device Exemption trial comparing ProDisc-L (Synthes Spine, West Chester, Pennsylvania) with 360° fusion for the treatment of single-level symptomatic disc degeneration. Of 80 patients randomized to 360° fusion after failure of non-operative care, 75 were treated on protocol with single-level fusions. Follow-up of this treatment cohort was 97% at 2 years and 75% at 5 years and serves as the basis for this report. Patients in the trial were required to have failure of at least 6 months of nonoperative care and in fact had failure of an average of 9 months of nonoperative treatment. The mean Oswestry Disability Index score indicated greater than 60% impairment. The mean entry-level pain score on a visual analog scale was greater than 8 of 10. After fusion, not only did patients have significant improvements in measurable clinical outcomes such as the Oswestry Disability Index score and pain score on a visual analog scale but there were also substantial improvements in their functional status and quality of life. Specifically, over 80% of patients in this study had improvements in recreational status that was maintained 5 years after index surgery, indicating substantial improvements in life quality that were not afforded by months of conservative care. The percentage of patients using narcotics at the 5-year follow-up visit was less than half the percentage of patients who had used narcotics as part of their prior conservative treatment. The 5-year results of this post hoc analysis of 75 patients involved in a multicenter, multi-surgeon trial support 360° fusion surgery as a predictable and lasting treatment option to improve pain and function in properly selected patients with mechanical degenerative disc disease. These improvements occurred dramatically immediately after surgery and have been maintained through the scope of this follow-up period, with 98% follow-up at 2 years and 75% of patients available at 5 years.

O1.3. A COMPUTATIONAL TRIAL-BY-TRIAL EEG ANALYSIS OF HIERARCHICAL PRECISION-WEIGHTED PREDICTION ERRORS

PubMed Central

Tomiello, Sara; Schöbi, Dario; Weber, Lilian; Haker, Helene; Sandra, Iglesias; Stephan, Klaas Enno

2018-01-01

Abstract Background Action optimisation relies on learning about past decisions and on accumulated knowledge about the stability of the environment. In Bayesian models of learning, belief updating is informed by multiple, hierarchically related, precision-weighted prediction errors (pwPEs). Recent work suggests that hierarchically different pwPEs may be encoded by specific neurotransmitters such as dopamine (DA) and acetylcholine (ACh). Abnormal dopaminergic and cholinergic modulation of N-methyl-D-aspartate (NMDA) receptors plays a central role in the dysconnection hypothesis, which considers impaired synaptic plasticity a central mechanisms in the pathophysiology of schizophrenia. Methods To probe the dichotomy between DA and ACh and to investigate timing parameters of pwPEs, we tested 74 healthy male volunteers performing a probabilistic reward associative learning task in which the contingency between cues and rewards changed over 160 trials between 0.8 and 0.2. Furthermore, the current study employed pharmacological interventions (amisulpride / biperiden / placebo) and genetic analyses (COMT and ChAT) to probe DA and ACh modulation of these computational quantities. The study was double-blind and between-subject. We inferred, from subject-specific behavioural data, a low-level choice PE about the reward outcome, a high-level PE about the probability of the outcome as well as the respective precision-weights (uncertainties) and used them, in a trial-by-trial analysis, to explain electroencephalogram (EEG) signals (64 channels). Behavioural data was modelled implementing three versions of the Hierarchical Gaussian Filter (HGF), a Rescorla-Wagner model, and a Sutton model with a dynamic learning rate. The computational trajectories of the winning model were used as regressors in single-subject trial-by-trial GLM analyses at the sensor level. The resulting parameter estimates were entered into 2nd-level ANOVAs. The reported results were family-wise error corrected at the peak-level (p<0.05) across the whole brain and time window (outcome phase: 0 - 500ms). Results A three-level HGF best explained the data and was used to compute the computational regressors for EEG analyses. We found a significant interaction between pharmacology and COMT for the high-level precision-weight (uncertainty). Specifically: - At 276 ms after outcome presentation the difference between Met/Met and Val/Met was more positive for amisulpride than for biperiden over occipital electrodes. - At 274ms and 278 ms after outcome presentation the difference between Met/Met and Val/Met was more negative over fronto-temporal electrodes for amisulpride than for placebo, and for amisulpride than for biperiden, respectively. No significant results were detected for the other computational quantities or for the ChAT gene. Discussion The differential effects of pharmacology on the processing of high-level precision-weight (uncertainty) were modulated by the DA-related gene COMT. Previous results linked high-level PEs to the cholinergic basal forebrain. One possible explanation for the current results is that high-level computational quantities are represented in cholinergic regions, which in turn are influenced by dopaminergic projections. In order to disentangle dopaminergic and cholinergic effects on synaptic plasticity further analyses will concentrate on biophysical models (e.g. DCM). This may prove useful in detecting pathophysiological subgroups and might therefore be of high relevance in a clinical setting.

The effect of Helicobacter pylori on vitamin B 12 blood levels in chronic renal failure patients: a single blind control trial.

PubMed

Khedmat, Hossein; Amini, Mohsen; Karbasi, Ashraf; Azizi, Reza

2013-07-01

Helicobacter pylori (HP) is a common infection worldwide and has been associated with severe morbidity. The level of vitamin B 12 in HP-infected chronic kidney disease (CKD) patients is reported to be lower than in the general population. The present study has been designed to evaluate the vitamin B 12 level in HP-infected CKD patients. We assessed the serum levels of vitamin B 12 in 50 CKD patients with positive HP serology, one and three months after the eradication of HP infection. There were significant differences between the serum levels of vitamin B 12 in the study patients before (806.98 ± 466.82) and after (760.36 ± 433.93) eradication treatment (P <0.001). We conclude that our study suggests the correlation between vitamin B 12 deficiency in CKD patients and the HP infection status.

Social Stories in mainstream schools for children with autism spectrum disorder: a feasibility randomised controlled trial.

PubMed

Marshall, David; Wright, Barry; Allgar, Victoria; Adamson, Joy; Williams, Christine; Ainsworth, Hannah; Cook, Liz; Varley, Danielle; Hackney, Lisa; Dempster, Paul; Ali, Shehzad; Trepel, Dominic; Collingridge Moore, Danielle; Littlewood, Elizabeth; McMillan, Dean

2016-08-11

To assess the feasibility of recruitment, retention, outcome measures and intervention training/delivery among teachers, parents and children. To calculate a sample size estimation for full trial. A single-centre, unblinded, cluster feasibility randomised controlled trial examining Social Stories delivered within a school environment compared with an attentional control. 37 primary schools in York, UK. 50 participants were recruited and a cluster randomisation approach by school was examined. Participants were randomised into the treatment group (n=23) or a waiting list control group (n=27). Acceptability and feasibility of the trial, intervention and of measurements required to assess outcomes in a definitive trial. An assessment of the questionnaire completion rates indicated teachers would be most appropriate to complete the primary outcome measure. 2 outcome measures: the Social Responsiveness Scale (SRS)-2 and a goal-based measure showed both the highest levels of completion rates (above 80%) at the primary follow-up point (6 weeks postintervention) and captured relevant social and behaviour outcomes. Power calculations were based on these 2 outcome measures leading to a total proposed sample size of 180 participant groups. Results suggest that a future trial would be feasible to conduct and could inform the policy and practice of using Social Stories in mainstream schools. ISRCTN96286707; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Do Mental Health Outpatient Services Meet Users' Needs? Trial to Identify Factors Associated with Higher Needs for Care.

PubMed

Dobrzynska, Ewelina; Rymaszewska, Joanna; Biecek, Przemyslaw; Kiejna, Andrzej

2016-05-01

The study was conducted to investigate the extent to which services meet patients' needs and identify the factors associated with higher needs. 174 outpatients were assessed using CANSAS, BPRS and GSDS. The total number of unmet needs in persons with psychotic, eating, personality and affective disorders was higher than in patients with anxiety disorders. Being single, positive symptoms, depression/anxiety, hospitalizations and high social disability accounted for 50 % of the variance in level of unmet need. Persons with eating and personality disorders reported similar level of unmet needs to those with psychotic and affective disorders. The best correlates of unmet needs were depression/anxiety and social disability.

Dynamic Reweighting of Auditory Modulation Filters.

PubMed

Joosten, Eva R M; Shamma, Shihab A; Lorenzi, Christian; Neri, Peter

2016-07-01

Sound waveforms convey information largely via amplitude modulations (AM). A large body of experimental evidence has provided support for a modulation (bandpass) filterbank. Details of this model have varied over time partly reflecting different experimental conditions and diverse datasets from distinct task strategies, contributing uncertainty to the bandwidth measurements and leaving important issues unresolved. We adopt here a solely data-driven measurement approach in which we first demonstrate how different models can be subsumed within a common 'cascade' framework, and then proceed to characterize the cascade via system identification analysis using a single stimulus/task specification and hence stable task rules largely unconstrained by any model or parameters. Observers were required to detect a brief change in level superimposed onto random level changes that served as AM noise; the relationship between trial-by-trial noisy fluctuations and corresponding human responses enables targeted identification of distinct cascade elements. The resulting measurements exhibit a dynamic complex picture in which human perception of auditory modulations appears adaptive in nature, evolving from an initial lowpass to bandpass modes (with broad tuning, Q∼1) following repeated stimulus exposure.

AAB and ABA Renewal as a Function of the Number of Extinction Trials in Conditioned Taste Aversion

ERIC Educational Resources Information Center

Rosas, Juan M.; Garcia-Gutierrez, Ana; Callejas-Aguilera, Jose E.

2007-01-01

Three experiments explored renewal in conditioned taste aversion after different amounts of extinction. In Experiment 1, three groups of rats received a single conditioning trial where a saccharin solution was paired with LiCl, followed by 3 extinction trials, and a two-trial test. Groups differed in the context where they received each of the…

Evidence Underpinning the Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Management Bundle (SEP-1): A Systematic Review.

PubMed

Pepper, Dominique J; Jaswal, Dharmvir; Sun, Junfeng; Welsh, Judith; Natanson, Charles; Eichacker, Peter Q

2018-04-17

This article has been corrected. To see what has changed, please read the Letter to the Editor and the authors' response. The original version (PDF) is appended to this article as a Supplement. The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1), the sepsis performance measure introduced in 2015 by the Centers for Medicare & Medicaid Services (CMS), requires the reporting of up to 5 hemodynamic interventions, as many as 141 tasks, and 3 hours to document for a single patient. To evaluate whether moderate- or high-level evidence shows that use of the 2015 SEP-1 or its hemodynamic interventions improves survival in adults with sepsis. PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov from inception to 28 November 2017 with no language restrictions. Randomized and observational studies of death among adults with sepsis who received versus those who did not receive either the entire SEP-1 bundle or 1 or more SEP-1 hemodynamic interventions, including serial lactate measurements; a fluid infusion of 30 mL/kg of body weight; and assessment of volume status and tissue perfusion with a focused examination, bedside cardiovascular ultrasonography, or fluid responsiveness testing. Two investigators independently extracted study data and assessed each study's risk of bias; 4 authors rated level of evidence by consensus using CMS criteria published in 2013. High- or moderate-level evidence required studies to have no confounders and low risk of bias. Of 56 563 references, 20 studies (18 reports) met inclusion criteria. One single-center observational study reported lower in-hospital mortality after implementation of the SEP-1 bundle. Sixteen studies (2 randomized and 14 observational) reported increased survival with serial lactate measurements or 30-mL/kg fluid infusions. None of the 17 studies were free of confounders or at low risk of bias. In 3 randomized trials, fluid responsiveness testing did not alter survival. Few trials, poor-quality and confounded studies, and no studies (with survival outcomes) of the focused examination or bedside cardiovascular ultrasonography. Use of the 2015 version of SEP-1 and 2013 version of CMS evidence criteria, both of which were updated in 2017. No high- or moderate-level evidence shows that SEP-1 or its hemodynamic interventions improve survival in adults with sepsis. National Institutes of Health. (PROSPERO: CRD42016052716).

CPAP Does Not Reduce Inflammatory Biomarkers in Patients With Coronary Artery Disease and Nonsleepy Obstructive Sleep Apnea: A Randomized Controlled Trial.

PubMed

Thunström, Erik; Glantz, Helena; Yucel-Lindberg, Tülay; Lindberg, Kristin; Saygin, Mustafa; Peker, Yüksel

2017-11-01

Obstructive sleep apnea (OSA) and enhanced vascular inflammation coexist in patients with coronary artery disease (CAD). Continuous positive airway pressure (CPAP) is first-line treatment for OSA with daytime sleepiness. This analysis of data from the RICCADSA (Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea) trial investigated the effects of CPAP on inflammatory markers in patients with CAD and nonsleepy OSA. This single-center, randomized, controlled, open-label trial enrolled consecutive revascularized patients with nonsleepy OSA (apnea-hypopnea index >15/h; Epworth Sleepiness Scale score <10). Levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were measured in blood samples taken at baseline (median 94 days after revascularization) and after 1 year of follow-up in patients randomized to CPAP or no-CPAP. A total of 220 patients with analyzable blood samples at baseline and 1 year were included. Baseline IL-6 levels were significantly lower in the CPAP versus no-CPAP group (median 3.1 pmol/L [interquartile range 1.3-5.7] vs. 4.2 pmol/L [2.0-8.9], respectively; p = .005). At 1-year follow-up, median IL-6 levels were significantly reduced in both groups (to 2.2 pmol/L [1.2-3.9] in the CPAP group and to 2.2 [1.2-4.7] in no-CPAP group; both p < .001 vs. baseline). IL-8, hs-CRP, and TNF-α did not change significantly from baseline. There was no association between CPAP adherence and changes in inflammatory marker levels. In patients with stable CAD and nonsleepy OSA, inflammatory biomarkers did not change significantly over time except for IL-6 levels, which reduced to the same extent in the CPAP and no-CPAP groups. ClinicalTrials.gov, ID: NCT00519597; researchweb.org, VGSKAS-4731. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Mediterranean diet cools down the inflammatory milieu in type 2 diabetes: the MÉDITA randomized controlled trial.

PubMed

Maiorino, Maria Ida; Bellastella, Giuseppe; Petrizzo, Michela; Scappaticcio, Lorenzo; Giugliano, Dario; Esposito, Katherine

2016-12-01

Mediterranean-style diets provide cardiovascular benefits and increase insulin sensitivity. There is little evidence that adherence to Mediterranean diet may influence the levels of the inflammatory milieu in type 2 diabetes. The aim of this study was to assess whether Mediterranean diet influences both C-reactive protein (CRP) and adiponectin in newly diagnosed type 2 diabetes, and whether adherence to Mediterranean diet affects their circulating levels. In a two-arm, single-center trial, 215 men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet (n = 108, 54 males and 54 females) or a low-fat diet (n = 107, 52 males and 55 females), with a total follow-up of 8.1 years. At baseline visit and at 1 year, body weight, HOMA index, CRP, and adiponectin and its fractions were assessed. Adherence to the diets was assessed by calculating the Mediterranean-diet score. At 1 year, CPR fell by 37 % and adiponectin rose by 43 % in the Mediterranean diet group, while remaining unchanged in the low-fat diet group. The pattern of adiponectin fractions (high and non-high molecular weight) showed a response similar to that of total adiponectin. Diabetic patients with the highest scores (6-9 points) of adherence to Mediterranean diet had lower circulating CRP level and higher circulating total adiponectin levels than the diabetic patients who scored <3 points on the scale (P = 0.001). The results of this randomized controlled trial demonstrate that Mediterranean diet cools down the inflammatory milieu of type 2 diabetes.

Bryostatin Effects on Cognitive Function and PKCɛ in Alzheimer's Disease Phase IIa and Expanded Access Trials.

PubMed

Nelson, Thomas J; Sun, Miao-Kun; Lim, Chol; Sen, Abhik; Khan, Tapan; Chirila, Florin V; Alkon, Daniel L

2017-01-01

Bryostatin 1, a potent activator of protein kinase C epsilon (PKCɛ), has been shown to reverse synaptic loss and facilitate synaptic maturation in animal models of Alzheimer's disease (AD), Fragile X, stroke, and other neurological disorders. In a single-dose (25 μg/m2) randomized double-blind Phase IIa clinical trial, bryostatin levels reached a maximum at 1-2 h after the start of infusion. In close parallel with peak blood levels of bryostatin, an increase of PBMC PKCɛ was measured (p = 0.0185) within 1 h from the onset of infusion. Of 9 patients with a clinical diagnosis of AD, of which 6 received drug and 3 received vehicle within a double-blind protocol, bryostatin increased the Mini-Mental State Examination (MMSE) score by +1.83±0.70 unit at 3 h versus -1.00±1.53 unit for placebo. Bryostatin was well tolerated in these AD patients and no drug-related adverse events were reported. The 25 μg/m2 administered dose was based on prior clinical experience with three Expanded Access advanced AD patients treated with bryostatin, in which return of major functions such as swallowing, vocalization, and word recognition were noted. In one Expanded Access patient trial, elevated PKCɛ levels closely tracked cognitive benefits in the first 24 weeks as measured by MMSE and ADCS-ADL psychometrics. Pre-clinical mouse studies showed effective activation of PKCɛ and increased levels of BDNF and PSD-95. Together, these Phase IIa, Expanded Access, and pre-clinical results provide initial encouragement for bryostatin 1 as a potential treatment for AD.

Social support and education groups for single mothers: a randomized controlled trial of a community-based program.

PubMed

Lipman, Ellen L; Boyle, Michael H

2005-12-06

Members of families headed by single mothers are at increased risk of psychosocial disadvantage and mental health problems. We assessed the effect of a community-based program of social support and education groups for single mothers of young children on maternal well-being and parenting. We recruited 116 single mothers of children 3 to 9 years old through community advertisements. Eligible mothers were randomly assigned either to participate in a 10-week program of group sessions (1.5 hours per week) offering social support and education, with a parallel children's activity group, or to receive a standard list of community resources and the option to participate in group sessions at the end of the follow-up period. Interviewers blinded to the randomization collected assessment data from all mothers at baseline and at 3 follow-up visits (immediately after the intervention and at 3 and 6 months after the intervention). Outcome measures were self-reported mood, self-esteem, social support and parenting. Between February 2000 and April 2003, the program was offered to 9 groups of single mothers. Most of the mothers in the trial reported high levels of financial and mental health problems. In the short term (after the intervention), mothers in the intervention group had improved scores for mood (p < 0.01, standardized effect = 0.55) and self-esteem (p < 0.05, standardized effect = 0.29) compared with mothers in the control group; scores for the other 2 measures did not differ between the groups. Growth curve analysis of program effects over the follow-up period showed improvement in all 4 outcomes, with no significant difference between the intervention and control groups. This community-based program of group sessions offering social support and education to low-income single mothers had positive short-term effects on mood and self-esteem but not on social support and parenting. Longer follow-up showed attenuation of these effects.

Using Covert Response Activation to Test Latent Assumptions of Formal Decision-Making Models in Humans.

PubMed

Servant, Mathieu; White, Corey; Montagnini, Anna; Burle, Borís

2015-07-15

Most decisions that we make build upon multiple streams of sensory evidence and control mechanisms are needed to filter out irrelevant information. Sequential sampling models of perceptual decision making have recently been enriched by attentional mechanisms that weight sensory evidence in a dynamic and goal-directed way. However, the framework retains the longstanding hypothesis that motor activity is engaged only once a decision threshold is reached. To probe latent assumptions of these models, neurophysiological indices are needed. Therefore, we collected behavioral and EMG data in the flanker task, a standard paradigm to investigate decisions about relevance. Although the models captured response time distributions and accuracy data, EMG analyses of response agonist muscles challenged the assumption of independence between decision and motor processes. Those analyses revealed covert incorrect EMG activity ("partial error") in a fraction of trials in which the correct response was finally given, providing intermediate states of evidence accumulation and response activation at the single-trial level. We extended the models by allowing motor activity to occur before a commitment to a choice and demonstrated that the proposed framework captured the rate, latency, and EMG surface of partial errors, along with the speed of the correction process. In return, EMG data provided strong constraints to discriminate between competing models that made similar behavioral predictions. Our study opens new theoretical and methodological avenues for understanding the links among decision making, cognitive control, and motor execution in humans. Sequential sampling models of perceptual decision making assume that sensory information is accumulated until a criterion quantity of evidence is obtained, from where the decision terminates in a choice and motor activity is engaged. The very existence of covert incorrect EMG activity ("partial error") during the evidence accumulation process challenges this longstanding assumption. In the present work, we use partial errors to better constrain sequential sampling models at the single-trial level. Copyright © 2015 the authors 0270-6474/15/3510371-15$15.00/0.

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio).

PubMed

Rattner, Barnett A; Horak, Katherine E; Lazarus, Rebecca S; Eisenreich, Karen M; Meteyer, Carol U; Volker, Steven F; Campton, Christopher M; Eisemann, John D; Johnston, John J

2012-04-01

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian short-eared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Meteyer, Carol U.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Johnston, John J.

2012-01-01

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/ or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian shorteared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Rating the methodological quality of single-subject designs and n-of-1 trials: introducing the Single-Case Experimental Design (SCED) Scale.

PubMed

Tate, Robyn L; McDonald, Skye; Perdices, Michael; Togher, Leanne; Schultz, Regina; Savage, Sharon

2008-08-01

Rating scales that assess methodological quality of clinical trials provide a means to critically appraise the literature. Scales are currently available to rate randomised and non-randomised controlled trials, but there are none that assess single-subject designs. The Single-Case Experimental Design (SCED) Scale was developed for this purpose and evaluated for reliability. Six clinical researchers who were trained and experienced in rating methodological quality of clinical trials developed the scale and participated in reliability studies. The SCED Scale is an 11-item rating scale for single-subject designs, of which 10 items are used to assess methodological quality and use of statistical analysis. The scale was developed and refined over a 3-year period. Content validity was addressed by identifying items to reduce the main sources of bias in single-case methodology as stipulated by authorities in the field, which were empirically tested against 85 published reports. Inter-rater reliability was assessed using a random sample of 20/312 single-subject reports archived in the Psychological Database of Brain Impairment Treatment Efficacy (PsycBITE). Inter-rater reliability for the total score was excellent, both for individual raters (overall ICC = 0.84; 95% confidence interval 0.73-0.92) and for consensus ratings between pairs of raters (overall ICC = 0.88; 95% confidence interval 0.78-0.95). Item reliability was fair to excellent for consensus ratings between pairs of raters (range k = 0.48 to 1.00). The results were replicated with two independent novice raters who were trained in the use of the scale (ICC = 0.88, 95% confidence interval 0.73-0.95). The SCED Scale thus provides a brief and valid evaluation of methodological quality of single-subject designs, with the total score demonstrating excellent inter-rater reliability using both individual and consensus ratings. Items from the scale can also be used as a checklist in the design, reporting and critical appraisal of single-subject designs, thereby assisting to improve standards of single-case methodology.

Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

PubMed Central

Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

2011-01-01

Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are warranted. Trial Registration www.controlled-trials.com ISRCTN47375023 PMID:21980373

Serum 24,25-dihydroxyvitamin D3 response to native vitamin D2 and D3 Supplementation in patients with chronic kidney disease on hemodialysis.

PubMed

Graeff-Armas, Laura A; Kaufmann, Martin; Lyden, Elizabeth; Jones, Glenville

2018-06-01

While vitamin D deficiency is common in patients with end stage renal disease on dialysis and treatment with Vitamin D 2 and Vitamin D 3 is becoming increasingly common in these patients, little is known about 24,25(OH) 2 D 3 metabolite production. Some authors report that the CYP24A1 enzyme is upregulated in CKD, but reports of low serum levels of 24,25(OH) 2 D 3 in these patients bring this into question. Lack of substrate or increased clearance of the metabolite have been proposed as possible causes. We report serum 24,25(OH) 2 D 3 levels from three controlled trials of Vitamin D 2 and Vitamin D 3 supplementation which reached adequate levels of 25(OH)D in patients with end stage renal disease on dialysis. 680 samples from three controlled trials of Vitamin D 2 or Vitamin D 3 supplementation in CKD Stage 5D were available for analysis. The trials used single doses of 50,000 IU Vitamin D 3 , or 50,000 IU Vitamin D 2 , or weekly doses of 10,000 IU or 20,000 IU Vitamin D 3 . Blood samples were drawn at baseline and frequently over the ensuing 3-4 months. Serum 25(OH)D and 24,25(OH) 2 D 3 levels were measured using a novel, very sensitive LC-MS/MS-based method involving derivatization with DMEQ-TAD. Linear mixed effect regression models were used to compare the 3 studies and the interventions within studies over time. The subjects given Vitamin D 3 had significant increases in 25(OH)D levels. Serum 24,25(OH) 2 D 3 levels were low at baseline in the renal patients and rose slightly with native vitamin D supplementation, but these levels were lower than reports of 24,25(OH) 2 D 3 in healthy populations. We conclude that the enzymatic activity of CYP24A1 is abnormal in end stage renal patients on dialysis. These trials were registered on clinicaltrials.govNCT00511225 on 8/1/2007; NCT01325610 on 1/17/2011; and NCT01675557 on 8/28/2012. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The immediate and long-term effects of exercise and patient education on physical, functional, and quality-of-life outcome measures after single-level lumbar microdiscectomy: a randomized controlled trial protocol.

PubMed

Selkowitz, David M; Kulig, Kornelia; Poppert, Elizabeth M; Flanagan, Sean P; Matthews, Ndidiamaka D; Beneck, George J; Popovich, John M; Lona, Jose R; Yamada, Kimiko A; Burke, Wendy S; Ervin, Carolyn; Powers, Christopher M

2006-08-25

Low back pain remains a costly quality-of-life-related health problem. Microdiscectomy is often the surgical procedure of choice for a symptomatic, single-level, lumbar disc herniation in younger and middle-aged adults. The question of whether a post-microdiscectomy exercise program enhances function, quality of life, and disability status has not been systematically explored. Thus, the overall purpose of this study is to assess immediate and long-term outcomes of an exercise program, developed at University of Southern California (USC), targeting the trunk and lower extremities (USC Spine Exercise Program) for persons who have undergone a single-level microdiscectomy for the first time. One hundred individuals between the ages of 18 and 60 who consent to undergo lumbar microdiscectomy will be recruited to participate in this study. Subjects will be randomly assigned to one of two groups: 1) one session of back care education, or 2) a back care education session followed by the 12-week USC Spine Exercise Program. The outcome examiners (evaluators), as well as the data managers, will be blinded to group allocation. Education will consist of a one-hour "one-on-one" session with the intervention therapist, guided by an educational booklet specifically designed for post-microdiscectomy care. This session will occur four to six weeks after surgery. The USC Spine Exercise Program consists of two parts: back extensor strength and endurance, and mat and upright therapeutic exercises. This exercise program is goal-oriented, performance-based, and periodized. It will begin two to three days after the education session, and will occur three times a week for 12 weeks. Primary outcome measures include the Oswestry Disability Questionnaire, Roland-Morris Disability Questionnaire, SF-36 quality of life assessment, Subjective Quality of Life Scale, 50-foot Walk, Repeated Sit-to-Stand, and a modified Sorensen test. The outcome measures in the study will be assessed before and after the 12-week post-surgical intervention program. Long-term follow up assessments will occur every six months beginning one year after surgery and ending five years after surgery. Immediate and long-term effects will be assessed using repeated measures multivariate analysis of variance (MANOVA). If significant interactions are found, one-way ANOVAs will be performed followed by post-hoc testing to determine statistically significant pairwise comparisons. We have presented the rationale and design for a randomized controlled trial evaluating the effectiveness of a treatment regimen for people who have undergone a single-level lumbar microdiscectomy.

Subthreshold muscle twitches dissociate oscillatory neural signatures of conflicts from errors.

PubMed

Cohen, Michael X; van Gaal, Simon

2014-02-01

We investigated the neural systems underlying conflict detection and error monitoring during rapid online error correction/monitoring mechanisms. We combined data from four separate cognitive tasks and 64 subjects in which EEG and EMG (muscle activity from the thumb used to respond) were recorded. In typical neuroscience experiments, behavioral responses are classified as "error" or "correct"; however, closer inspection of our data revealed that correct responses were often accompanied by "partial errors" - a muscle twitch of the incorrect hand ("mixed correct trials," ~13% of the trials). We found that these muscle twitches dissociated conflicts from errors in time-frequency domain analyses of EEG data. In particular, both mixed-correct trials and full error trials were associated with enhanced theta-band power (4-9Hz) compared to correct trials. However, full errors were additionally associated with power and frontal-parietal synchrony in the delta band. Single-trial robust multiple regression analyses revealed a significant modulation of theta power as a function of partial error correction time, thus linking trial-to-trial fluctuations in power to conflict. Furthermore, single-trial correlation analyses revealed a qualitative dissociation between conflict and error processing, such that mixed correct trials were associated with positive theta-RT correlations whereas full error trials were associated with negative delta-RT correlations. These findings shed new light on the local and global network mechanisms of conflict monitoring and error detection, and their relationship to online action adjustment. © 2013.

Information on center characteristics as costs' determinants in multicenter clinical trials: is modeling center effect worth the effort?

PubMed

Petrinco, Michele; Pagano, Eva; Desideri, Alessandro; Bigi, Riccardo; Ghidina, Marco; Ferrando, Alberto; Cortigiani, Lauro; Merletti, Franco; Gregori, Dario

2009-01-01

Several methodological problems arise when health outcomes and resource utilization are collected at different sites. To avoid misleading conclusions in multi-center economic evaluations the center effect needs to be taken into adequate consideration. The aim of this article is to compare several models, which make use of a different amount of information about the enrolling center. To model the association of total medical costs with the levels of two sets of covariates, one at patient and one at center level, we considered four statistical models, based on the Gamma model in the class of the Generalized Linear Models with a log link, which use different amount of information on the enrolling centers. Models were applied to Cost of Strategies after Myocardial Infarction data, an international randomized trial on costs of uncomplicated acute myocardial infarction (AMI). The simple center effect adjustment based on a single random effect results in a more conservative estimation of the parameters as compared with approaches which make use of deeper information on the centers characteristics. This study shows, with reference to a real multicenter trial, that center information cannot be neglected and should be collected and inserted in the analysis, better in combination with one or more random effect, taking into account in this way also the heterogeneity among centers because of unobserved centers characteristics.

Comparing cluster-level dynamic treatment regimens using sequential, multiple assignment, randomized trials: Regression estimation and sample size considerations.

PubMed

NeCamp, Timothy; Kilbourne, Amy; Almirall, Daniel

2017-08-01

Cluster-level dynamic treatment regimens can be used to guide sequential treatment decision-making at the cluster level in order to improve outcomes at the individual or patient-level. In a cluster-level dynamic treatment regimen, the treatment is potentially adapted and re-adapted over time based on changes in the cluster that could be impacted by prior intervention, including aggregate measures of the individuals or patients that compose it. Cluster-randomized sequential multiple assignment randomized trials can be used to answer multiple open questions preventing scientists from developing high-quality cluster-level dynamic treatment regimens. In a cluster-randomized sequential multiple assignment randomized trial, sequential randomizations occur at the cluster level and outcomes are observed at the individual level. This manuscript makes two contributions to the design and analysis of cluster-randomized sequential multiple assignment randomized trials. First, a weighted least squares regression approach is proposed for comparing the mean of a patient-level outcome between the cluster-level dynamic treatment regimens embedded in a sequential multiple assignment randomized trial. The regression approach facilitates the use of baseline covariates which is often critical in the analysis of cluster-level trials. Second, sample size calculators are derived for two common cluster-randomized sequential multiple assignment randomized trial designs for use when the primary aim is a between-dynamic treatment regimen comparison of the mean of a continuous patient-level outcome. The methods are motivated by the Adaptive Implementation of Effective Programs Trial which is, to our knowledge, the first-ever cluster-randomized sequential multiple assignment randomized trial in psychiatry.

Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.

PubMed

Rowan, Kathryn M; Angus, Derek C; Bailey, Michael; Barnato, Amber E; Bellomo, Rinaldo; Canter, Ruth R; Coats, Timothy J; Delaney, Anthony; Gimbel, Elizabeth; Grieve, Richard D; Harrison, David A; Higgins, Alisa M; Howe, Belinda; Huang, David T; Kellum, John A; Mouncey, Paul R; Music, Edvin; Peake, Sandra L; Pike, Francis; Reade, Michael C; Sadique, M Zia; Singer, Mervyn; Yealy, Donald M

2017-06-08

After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158 .).

Distribution of guidance models for cardiac resynchronization therapy in the setting of multi-center clinical trials

NASA Astrophysics Data System (ADS)

Rajchl, Martin; Abhari, Kamyar; Stirrat, John; Ukwatta, Eranga; Cantor, Diego; Li, Feng P.; Peters, Terry M.; White, James A.

2014-03-01

Multi-center trials provide the unique ability to investigate novel techniques across a range of geographical sites with sufficient statistical power, the inclusion of multiple operators determining feasibility under a wider array of clinical environments and work-flows. For this purpose, we introduce a new means of distributing pre-procedural cardiac models for image-guided interventions across a large scale multi-center trial. In this method, a single core facility is responsible for image processing, employing a novel web-based interface for model visualization and distribution. The requirements for such an interface, being WebGL-based, are minimal and well within the realms of accessibility for participating centers. We then demonstrate the accuracy of our approach using a single-center pacemaker lead implantation trial with generic planning models.

[The P300 based brain-computer interface: effect of stimulus position in a stimulus train].

PubMed

Ganin, I P; Shishkin, S L; Kochetova, A G; Kaplan, A Ia

2012-01-01

The P300 brain-computer interface (BCI) is currently the most efficient BCI. This interface is based on detection of the P300 wave of the brain potentials evoked when a symbol related to the intended input is highlighted. To increase operation speed of the P300 BCI, reduction of the number of stimuli repetitions is needed. This reduction leads to increase of the relative contribution to the input symbol detection from the reaction to the first target stimulus. It is known that the event-related potentials (ERP) to the first stimulus presentations can be different from the ERP to stimuli presented latter. In particular, the amplitude of responses to the first stimulus presentations is often increased, which is beneficial for their recognition by the BCI. However, this effect was not studied within the BCI framework. The current study examined the ERP obtained from healthy participants (n = 14) in the standard P300 BCI paradigm using 10 trials, as well as in the modified P300 BCI with stimuli presented on moving objects in triple-trial (n = 6) and single-trial (n = 6) stimulation modes. Increased ERP amplitude was observed in response to the first target stimuli in both conditions, as well as in the single-trial mode comparing to triple-trial. We discuss the prospects of using the specific features of the ERP to first stimuli and the single-trial ERP for optimizing the high-speed modes in the P300 BCIs.

Postprandial improvement in insulin sensitivity after a single exercise session in adolescents with low aerobic fitness and physical activity.

PubMed

Short, Kevin R; Pratt, Lauren V; Teague, April M; Man, Chiara Dalla; Cobelli, Claudio

2013-03-01

The purpose of this study was to determine the acute and residual impact of a single exercise bout on meal glucose control in adolescents with habitually low physical activity. Twelve adolescents (seven females/five males, 14 ± 2 yr) completed three trials. One trial [No Exercise (No Ex)] was completed after refraining from vigorous activity for ≥ 3 d. On the other two trials, a 45-min aerobic exercise bout at 75% peak heart rate was performed either 17-h Prior Day Exercise (Prior Day Ex) trial or 1-h Same Day Exercise (Same Day Ex) trial before consuming the test meal (2803 kJ, 45/40/15% energy as carbohydrate/fat/protein, respectively). Compared to No Ex, insulin sensitivity (SI) (minimal model analysis) was increased by 45% (p < 0.03) and 78% (p < 0.01) on the Prior Day Ex and Same Day Ex trials, respectively. This improvement in glucose control was supported by corresponding reductions in the net area under the curve for glucose, insulin, and c-peptide, although there was no change in postprandial suppression of fatty acids. These results show that SI is improved with a single bout of moderate intensity exercise in adolescents with habitually low physical activity and that the residual beneficial effect of exercise lasts at least 17 h. This finding highlights the plasticity of exercise responses in youth and the importance of daily exercise for metabolic health. © 2012 John Wiley & Sons A/S.

Rigorous tests of gene-environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression.

PubMed

LoParo, Devon; Johansson, Ada; Walum, Hasse; Westberg, Lars; Santtila, Pekka; Waldman, Irwin

2016-07-01

Naturalistic studies of gene-environment interactions (G X E) have been plagued by several limitations, including difficulty isolating specific environmental risk factors from other correlated aspects of the environment, gene-environment correlation (rGE ), and the use of a single genetic variant to represent the influence of a gene. We present results from 235 Finnish young men in two lab studies of aggression and alcohol challenge that attempt to redress these limitations of the extant G X E literature. Specifically, we use a latent variable modeling approach in an attempt to more fully account for genetic variation across the oxytocin receptor gene (OXTR) and to robustly test its main effects on aggression and its interaction with alcohol exposure. We also modeled aggression as a latent variable comprising various indices, including the average and maximum levels of aggression, the earliest trial on which aggression was expressed, and the proportion of trials on which the minimum and maximum levels of aggression were expressed. The best fitting model for the genetic variation across OXTR included six factors derived from an exploratory factor analysis, roughly corresponding to six haplotype blocks. Aggression levels were higher on trials in which participants were administered alcohol, won, or were provoked. There was a significant main effect of OXTR on aggression across studies after controlling for covariates. The interaction of OXTR and alcohol was also significant across studies, such that OXTR had stronger effects on aggression in the alcohol administration condition. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Intravenous iron vs blood for acute post-partum anaemia (IIBAPPA): a prospective randomised trial.

PubMed

Chua, Seng; Gupta, Sarika; Curnow, Jennifer; Gidaszewski, Beata; Khajehei, Marjan; Diplock, Hayley

2017-12-19

Acute post-partum anaemia can be associated with significant morbidity including a predisposition for postnatal depression. Lack of clear practice guidelines means a number of women are treated with multiple blood transfusions. Intravenous iron has the potential to limit the need for multiple blood transfusions but its role in the post-partum setting is unclear. IIBAPPA is a multi-centre randomised non-inferiority trial. Women with a primary post-partum haemorrhage (PPH) >1000 mL and resultant haemoglobin (Hb) 5.5-8.0 g/dL after resuscitation with ongoing symptomatic anaemia who are otherwise stable (no active bleeding) are eligible to participate. Patients with sepsis or conditions necessitating rapid Hb restoration are excluded. Eligible participants are randomised to receive a blood transfusion or a single dose of intravenous iron polymaltose calculated using the Ganzoni formula. Primary outcome measures include Hb, Ferritin and C-Reactive Protein levels on Day 7. Secondary outcomes evaluate (i) Hb, Ferritin and CRP levels on Day 14, 28, (ii) anaemia symptoms on Day 0, 7, 14 and 28 using structured health related quality of life questionnaires, (iii) treatment safety by assessing adverse reactions and infection endpoints and (iv) the quantitative impact of anaemia on breast feeding quality using a hospital designed questionnaire. If equivalence in Hb and ferritin levels, symptom scores and safety endpoints is demonstrated, intravenous iron may become the preferred treatment for women with acute post-partum anaemia to minimise transfusion reactions and costs. Australian and New Zealand Clinical Trials Registry: ACTRN12615001370594 on 16th December, 2015 (prospective approval).

Effect of trelagliptin on vascular endothelial functions and serum adiponectin level in patients with type 2 diabetes: a preliminary single-arm prospective pilot study.

PubMed

Ida, Satoshi; Murata, Kazuya; Betou, Katunori; Kobayashi, Chiaki; Ishihara, Yuki; Imataka, Kanako; Uchida, Akihiro; Monguchi, Kou; Kaneko, Ryutaro; Fujiwara, Ryoko; Takahashi, Hiroka

2016-11-04

Trelagliptin, an oral DPP-4 inhibitor, which is administered once per week and characterized by a long half-life in blood. The effects of trelagliptin on vascular endothelial functions have not been clarified to date. The objective of the present study was to examine the effects of trelagliptin on vascular endothelial functions in patients with type 2 diabetes mellitus (DM) using flow-mediated dilatation (FMD), adiponectin, and asymmetric dimethylarginine (ADMA) as evaluation indicators. This study was a preliminary single-arm prospective pilot study. The subjects of this study were type 2 DM patients aged 20-74 years, who visited our outpatient department. The patients were treated with trelagliptin, and their FMD, adiponectin, and ADMA levels were measured at baseline and at 12 weeks after initial treatment to determine the changes during the study period. A total of 27 patients, excluding three dropouts, were included in the population for analysis. Trelagliptin treatment showed no significant changes in FMD (2.42 ± 2.7% at baseline vs. 2.66 ± 3.8% post-treatment, P = 0.785) and ADMA (0.41 ± 0.0 µg/mL at baseline vs. 0.40 ± 0.0 µg/mL post-treatment, P = 0.402). Trelagliptin treatment resulted in a significant increase of serum adiponectin level (7.72 ± 6.9 µg/mL at baseline vs. 8.82 ± 8.3 µg/mL post-treatment, P < 0.002). In this pilot study, trelagliptin treatment showed no significant changes in FMD. On the other hand, it was believed that trelagliptin treatment may increase serum adiponectin level. Trial Registration http://www.umin.ac.jp (Trial ID UMIN000018311).

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.

A Bayesian-frequentist two-stage single-arm phase II clinical trial design.

PubMed

Dong, Gaohong; Shih, Weichung Joe; Moore, Dirk; Quan, Hui; Marcella, Stephen

2012-08-30

It is well-known that both frequentist and Bayesian clinical trial designs have their own advantages and disadvantages. To have better properties inherited from these two types of designs, we developed a Bayesian-frequentist two-stage single-arm phase II clinical trial design. This design allows both early acceptance and rejection of the null hypothesis ( H(0) ). The measures (for example probability of trial early termination, expected sample size, etc.) of the design properties under both frequentist and Bayesian settings are derived. Moreover, under the Bayesian setting, the upper and lower boundaries are determined with predictive probability of trial success outcome. Given a beta prior and a sample size for stage I, based on the marginal distribution of the responses at stage I, we derived Bayesian Type I and Type II error rates. By controlling both frequentist and Bayesian error rates, the Bayesian-frequentist two-stage design has special features compared with other two-stage designs. Copyright © 2012 John Wiley & Sons, Ltd.

Birth weight and prematurity in infants with single ventricle physiology: pediatric heart network infant single ventricle trial screened population.

PubMed

Williams, Richard V; Ravishankar, Chitra; Zak, Victor; Evans, Frank; Atz, Andrew M; Border, William L; Levine, Jami; Li, Jennifer S; Mahony, Lynn; Mital, Seema; Pearson, Gail D; Prakash, Ashwin; Hsu, Daphne T

2010-01-01

Although congenital heart disease is associated with low birth weight and prematurity, there is little information about these birth outcomes in infants with single ventricle physiology. We describe the birth outcomes (i.e., gestational age and birth weight) in neonates with single ventricle physiology screened for enrollment in the Pediatric Heart Network's Infant Single Ventricle Trial, compare these outcomes with US norms, and examine the association of birth outcomes with anatomic diagnosis and race. All neonates with single ventricle physiology presenting to Infant Single Ventricle Trial centers were screened for enrollment. Demographic data and anatomic diagnoses were obtained from medical records. A total of 1245 neonates with single ventricle physiology were screened at 10 centers (63 to 266 per center). Diagnoses included hypoplastic left heart syndrome in 49%, unbalanced atrioventricular septal defect in 12%, and tricuspid atresia in 9%. Preterm birth occurred in 16% of neonates with single ventricle physiology vs. 12% in normal neonates (P < .001), low birth weight (<2.5 kg) in 18% vs. 8% in normals (P < .001), and small for gestational age (<10th percentile by definition) in 22% vs. 10% in normals (P < .001). A genetic syndrome was reported in 8%. The percentage of preterm birth, low birth weight, and small for gestational age was similar between screened neonates with and without hypoplastic left heart syndrome. In this large, contemporary cohort of neonates with single ventricle physiology, rates of preterm birth, low birth weight, and small for gestational age were higher than in the general population, but similar between screened neonates with and without hypoplastic left heart syndrome.

Analysis of phase II studies on targeted agents and subsequent phase III trials: what are the predictors for success?

PubMed

Chan, John K; Ueda, Stefanie M; Sugiyama, Valerie E; Stave, Christopher D; Shin, Jacob Y; Monk, Bradley J; Sikic, Branimir I; Osann, Kathryn; Kapp, Daniel S

2008-03-20

To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors. We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models. Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial. In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.

Biomarker and Clinical Trial Design Support for Disease-Modifying Therapies: Report of a Survey of the EU/US: Alzheimer's Disease Task Force.

PubMed

Cummings, J; Fox, N; Vellas, B; Aisen, P; Shan, G

2018-01-01

Disease-modifying therapies are urgently needed for the treatment of Alzheimer's disease (AD). The European Union/United States (EU/US) Task Force represents a broad range of stakeholders including biopharma industry personnel, academicians, and regulatory authorities. The EU/US Task Force represents a community of knowledgeable individuals who can inform views of evidence supporting disease modification and the development of disease-modifying therapies (DMTs). We queried their attitudes toward clinical trial design and biomarkers in support of DMTs. A survey of members of the EU/US Alzheimer's Disease Task Force was conducted. Ninety-three members (87%) responded. The details were analyzed to understand what clinical trial design and biomarker data support disease modification. Task Force members favored the parallel group design compared to delayed start or staggered withdrawal clinical trial designs to support disease modification. Amyloid biomarkers were regarded as providing mild support for disease modification while tau biomarkers were regarded as providing moderate support. Combinations of biomarkers, particularly combinations of tau and neurodegeneration, were regarded as providing moderate to marked support for disease modification and combinations of all three classes of biomarkers were regarded by a majority as providing marked support for disease modification. Task Force members considered that evidence derived from clinical trials and biomarkers supports clinical meaningfulness of an intervention, and when combined with a single clinical trial outcome, nearly all regarded the clinical trial design or biomarker evidence as supportive of disease modification. A minority considered biomarker evidence by itself as indicative of disease modification in prevention trials. Levels of evidence (A,B,C) were constructed based on these observations. The survey indicates the view of knowledgeable stakeholders regarding evidence derived from clinical trial design and biomarkers in support of disease modification. Results of this survey can assist in designing clinical trials of DMTs.

Characteristics and trends of clinical trials funded by the National Institutes of Health between 2005 and 2015.

PubMed

Gresham, Gillian K; Ehrhardt, Stephan; Meinert, Jill L; Appel, Lawrence J; Meinert, Curtis L

2018-02-01

Background The National Institutes of Health is one of the largest biomedical research agencies in the world. Clinical trials are an important component of National Institutes of Health research efforts. Given the recent updates in National Institutes of Health trial reporting requirements, more information regarding the current state of National Institutes of Health-funded clinical trials is warranted. The objective of this analysis was to describe characteristics and trends of clinical trials funded by the National Institutes of Health over time and by Institutes and Centers of the National Institutes of Health. Methods Interventional studies funded by the National Institutes of Health and registered in ClinicalTrials.gov between 2005 and 2015 were included in the analysis. Trials were identified from the 27 March 2016 Clinical Trials Transformation Initiative Aggregate Analysis of ClinicalTrials.gov database. A descriptive analysis of trials by year and National Institutes of Health Institute/Center was performed. Results There were 12,987 National Institutes of Health-funded clinical trials registered between 2005 and 2015. There were 1,580, 1,116, and 930 trials registered in 2005, 2010, and 2015, respectively. The majority were early-development trials (phases 0, 1, or 2; 53%), randomized (61%), and single-center (63%). Trial demographics have remained unchanged over time. Median trial sample size was 64 (interquartile range 29-192) with 10% of trials enrolling ≥500 participants. Most trials were completed within 5 years of enrollment start (69%). Trial characteristics varied considerably across National Institutes of Health Institutes and Centers. Results were reported under the assumptions that most National Institutes of Health-funded trials are registered in ClinicalTrials.gov and that trials are being registered completely and accurately. Conclusion In conclusion, there has been a decline in the number of trials being funded over time, explained in part by a relatively constant budget, increases in trial costs, or other factors that cannot be quantified. National Institutes of Health-funded trials are relatively small and tend to be single-centered. There are substantial differences in the number and types of trials done by Institutes and Centers within the National Institutes of Health.

Tai Chi exercise in improving cardiorespiratory capacity.

PubMed

Thornton, Everard W

2008-01-01

To evaluate evidence relating to effects of Tai Chi on cardiovascular outcomes, with emphasis on randomised control designs. Studies reviewed in 2004 were re-examined, together with more recent controlled trials of Tai Chi relating to cardiovascular outcome. The analysis provided comment on problems associated with randomised control design, including sources of bias in such trials. With a single exception, data support reduction of baseline systolic/diastolic blood pressure (BP). While there may be positive bias in these studies, data are from diverse ethnic groups, different gender, age, and level of functional ability. There are no data relating to BP reactive change to subsequent stressors. Few studies consider potential mediating mechanisms through which Tai Chi may provide these benefits. Caution is advocated in using randomised controlled trials as the only effective type of study. Such designs are difficult to conduct and effective trials are more likely given a better understanding of the mediating mechanism(s) through which benefits may be derived. It is currently unclear how changes in BP are derived. Some data indicate a shift to increased vagal relative to sympathetic dominance and there may be other potential physiological mediators. No study has examined relationships between potential psychological gains such as self-efficacy and BP change, or individual differences in outcomes.

Interventions to reduce accidents in childhood: a systematic review.

PubMed

Barcelos, Raquel S; Del-Ponte, Bianca; Santos, Iná S

2017-12-30

To review the literature on interventions planned to prevent the incidence of injuries in childhood. The PubMed, Web of Science, and Bireme databases were searched by two independent reviewers, employing the single terms accidents, accident, injuries, injury, clinical trial, intervention, educational intervention, and multiple interventions, and their combinations, present in the article title or abstract, with no limits except period of publication (2006-2016) and studies in human subjects. Initially, 11,097 titles were located. Fifteen articles were selected for the review. Eleven were randomized trials (four carried out at the children's households, five in pediatric healthcare services, and two at schools), and four were non-randomized trials carried out at the children's households. Four of the randomized trials were analyzed by intention-to-treat and a protective effect of the intervention was observed: decrease in the number of risk factors, decrease in the number of medical consultations due to injuries, decrease in the prevalence of risk behaviors, and increase of the parents' knowledge regarding injury prevention in childhood. Traumatic injuries in childhood are amenable to primary prevention through strategies that consider the child's age and level of development, as well as structural aspects of the environment. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Effects of Visual Complexity and Sublexical Information in the Occipitotemporal Cortex in the Reading of Chinese Phonograms: A Single-Trial Analysis with MEG

ERIC Educational Resources Information Center

Hsu, Chun-Hsien; Lee, Chia-Ying; Marantz, Alec

2011-01-01

We employ a linear mixed-effects model to estimate the effects of visual form and the linguistic properties of Chinese characters on M100 and M170 MEG responses from single-trial data of Chinese and English speakers in a Chinese lexical decision task. Cortically constrained minimum-norm estimation is used to compute the activation of M100 and M170…

Reporting non-adherence in cluster randomised trials: A systematic review.

PubMed

Agbla, Schadrac C; DiazOrdaz, Karla

2018-06-01

Treatment non-adherence in randomised trials refers to situations where some participants do not receive their allocated treatment as intended. For cluster randomised trials, where the unit of randomisation is a group of participants, non-adherence may occur at the cluster or individual level. When non-adherence occurs, randomisation no longer guarantees that the relationship between treatment receipt and outcome is unconfounded, and the power to detect the treatment effects in intention-to-treat analysis may be reduced. Thus, recording adherence and estimating the causal treatment effect adequately are of interest for clinical trials. To assess the extent of reporting of non-adherence issues in published cluster trials and to establish which methods are currently being used for addressing non-adherence, if any, and whether clustering is accounted for in these. We systematically reviewed 132 cluster trials published in English in 2011 previously identified through a search in PubMed. One-hundred and twenty three cluster trials were included in this systematic review. Non-adherence was reported in 56 cluster trials. Among these, 19 reported a treatment efficacy estimate: per protocol in 15 and as treated in 4. No study discussed the assumptions made by these methods, their plausibility or the sensitivity of the results to deviations from these assumptions. The year of publication of the cluster trials included in this review (2011) could be considered a limitation of this study; however, no new guidelines regarding the reporting and the handling of non-adherence for cluster trials have been published since. In addition, a single reviewer undertook the data extraction. To mitigate this, a second reviewer conducted a validation of the extraction process on 15 randomly selected reports. Agreement was satisfactory (93%). Despite the recommendations of the Consolidated Standards of Reporting Trials statement extension to cluster randomised trials, treatment adherence is under-reported. Among the trials providing adherence information, there was substantial variation in how adherence was defined, handled and reported. Researchers should discuss the assumptions required for the results to be interpreted causally and whether these are scientifically plausible in their studies. Sensitivity analyses to study the robustness of the results to departures from these assumptions should be performed.

Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup.

PubMed

Hardarson, Thorir; Bungum, Mona; Conaghan, Joe; Meintjes, Marius; Chantilis, Samuel J; Molnar, Laszlo; Gunnarsson, Kristina; Wikland, Matts

2015-12-01

To study whether a culture medium that allows undisturbed culture supports human embryo development to the blastocyst stage equivalently to a well-established sequential media. Randomized, double-blinded sibling trial. Independent in vitro fertilization (IVF) clinics. One hundred twenty-eight patients, with 1,356 zygotes randomized into two study arms. Embryos randomly allocated into two study arms to compare embryo development on a time-lapse system using a single-step medium or sequential media. Percentage of good-quality blastocysts on day 5. Percentage of day 5 good-quality blastocysts was 21.1% (standard deviation [SD] ± 21.6%) and 22.2% (SD ± 22.1%) in the single-step time-lapse medium (G-TL) and the sequential media (G-1/G-2) groups, respectively. The mean difference (-1.2; 95% CI, -6.0; 3.6) between the two media systems for the primary end point was less than the noninferiority margin of -8%. There was a statistically significantly lower number of good-quality embryos on day 3 in the G-TL group [50.7% (SD ± 30.6%) vs. 60.8% (SD ± 30.7%)]. Four out of the 11 measured morphokinetic parameters were statistically significantly different for the two media used. The mean levels of ammonium concentration in the media at the end of the culture period was statistically significantly lower in the G-TL group as compared with the G-2 group. We have shown that a single-step culture medium supports blastocyst development equivalently to established sequential media. The ammonium concentrations were lower in the single-step media, and the measured morphokinetic parameters were modified somewhat. NCT01939626. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

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

Randomized controlled trial of multidisciplinary team stress and performance in immersive simulation for management of infant in shock: study protocol.

PubMed

Ghazali, Daniel Aiham; Ragot, Stéphanie; Breque, Cyril; Guechi, Youcef; Boureau-Voultoury, Amélie; Petitpas, Franck; Oriot, Denis

2016-03-25

Human error and system failures continue to play a substantial role in adverse outcomes in healthcare. Simulation improves management of patients in critical condition, especially if it is undertaken by a multidisciplinary team. It covers technical skills (technical and therapeutic procedures) and non-technical skills, known as Crisis Resource Management. The relationship between stress and performance is theoretically described by the Yerkes-Dodson law as an inverted U-shaped curve. Performance is very low for a low level of stress and increases with an increased level of stress, up to a point, after which performance decreases and becomes severely impaired. The objectives of this randomized trial are to study the effect of stress on performance and the effect of repeated simulation sessions on performance and stress. This study is a single-center, investigator-initiated randomized controlled trial including 48 participants distributed in 12 multidisciplinary teams. Each team is made up of 4 persons: an emergency physician, a resident, a nurse, and an ambulance driver who usually constitute a French Emergency Medical Service team. Six multidisciplinary teams are planning to undergo 9 simulation sessions over 1 year (experimental group), and 6 multidisciplinary teams are planning to undergo 3 simulation sessions over 1 year (control group). Evidence of the existence of stress will be assessed according to 3 criteria: biological, electrophysiological, and psychological stress. The impact of stress on overall team performance, technical procedure and teamwork will be evaluated. Participant self-assessment of the perceived impact of simulations on clinical practice will be collected. Detection of post-traumatic stress disorder will be performed by self-assessment questionnaire on the 7(th) day and after 1 month. We will concomitantly evaluate technical and non-technical performance, and the impact of stress on both. This is the first randomized trial studying repetition of simulation sessions and its impact on both clinical performance and stress, which is explored by objective and subjective assessments. We expect that stress decreases team performance and that repeated simulation will increase it. We expect no variation of stress parameters regardless of the level of performance. ClinicalTrials.gov registration number NCT02424890.

Involving patients in setting priorities for healthcare improvement: a cluster randomized trial

PubMed Central

2014-01-01

Background Patients are increasingly seen as active partners in healthcare. While patient involvement in individual clinical decisions has been extensively studied, no trial has assessed how patients can effectively be involved in collective healthcare decisions affecting the population. The goal of this study was to test the impact of involving patients in setting healthcare improvement priorities for chronic care at the community level. Methods Design: Cluster randomized controlled trial. Local communities were randomized in intervention (priority setting with patient involvement) and control sites (no patient involvement). Setting: Communities in a canadian region were required to set priorities for improving chronic disease management in primary care, from a list of 37 validated quality indicators. Intervention: Patients were consulted in writing, before participating in face-to-face deliberation with professionals. Control: Professionals established priorities among themselves, without patient involvement. Participants: A total of 172 individuals from six communities participated in the study, including 83 chronic disease patients, and 89 health professionals. Outcomes: The primary outcome was the level of agreement between patients’ and professionals’ priorities. Secondary outcomes included professionals’ intention to use the selected quality indicators, and the costs of patient involvement. Results Priorities established with patients were more aligned with core generic components of the Medical Home and Chronic Care Model, including: access to primary care, self-care support, patient participation in clinical decisions, and partnership with community organizations (p < 0.01). Priorities established by professionals alone placed more emphasis on the technical quality of single disease management. The involvement intervention fostered mutual influence between patients and professionals, which resulted in a 41% increase in agreement on common priorities (95%CI: +12% to +58%, p < 0.01). Professionals’ intention to use the selected quality indicators was similar in intervention and control sites. Patient involvement increased the costs of the prioritization process by 17%, and required 10% more time to reach consensus on common priorities. Conclusions Patient involvement can change priorities driving healthcare improvement at the population level. Future research should test the generalizability of these findings to other contexts, and assess its impact on patient care. Trial registration The Netherlands National Trial Register #NTR2496. PMID:24555508

The Efficacy of a Web-Based Screening and Brief Intervention for Reducing Alcohol Consumption Among Japanese Problem Drinkers: Protocol for a Single-Blind Randomized Controlled Trial.

PubMed

Hamamura, Toshitaka; Suganuma, Shinichiro; Takano, Ayumi; Matsumoto, Toshihiko; Shimoyama, Haruhiko

2018-05-30

The literature shows that computer-delivered interventions with personalized normative feedback can reduce problem drinking for up to 6 months in the West. Meanwhile, no studies have been conducted to examine the effects of such interventions among Japanese problem drinkers. Possible moderators associated with effectiveness of the intervention need to be also explored. The purpose of this study is to conduct a trial and examine the efficacy of a brief intervention with personal normative feedback and psychoeducation on several measures of alcohol consumption among Japanese problem drinkers. Additionally, this study will examine whether the level of alcohol use disorder and beliefs about the physical and psychological outcomes of drinking moderate the effect of the intervention on outcome measures. This study will conduct a single-blind, 2-armed randomized controlled trial. Japanese adults with an Alcohol Use Disorder Identification Test score of 8 or higher will be enrolled in the trial. Participants allocated to the intervention group will receive the intervention immediately after the baseline measurements, and participants allocated to the waitlist group will receive the intervention at the end of the trial. Outcome measures include drinking quantity, drinking frequency, and alcohol-related consequences. Follow-up assessment will take place at 1 month, 2 months, and 6 months following the baseline measurement. The authors will not know the group allocation during trial. The authors will plan to collect a sample of 600 participants. Mixed-effect analyses of variance will be used to examine the main effects of condition, the main effects of time, and the interaction effects between condition and time on outcome variables. Enrollment for the trial began on January 6, 2018 and data are expected to be available by August 2018. This study will contribute to the literature by demonstrating the efficacy of Web-based screenings and brief interventions among Japanese problem drinkers and indicating several possible moderators between the intervention and outcomes. This type of Web-based brief intervention has the possibility of being implemented in Japanese schools and workplaces as a prevention tool. UMIN Clinical Trials Registry R000034388; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi? recptno=R000034388 (Archived by WebCite at http://www.webcitation.org/6xmOoTfTI). RR1-10.2196/10650. ©Toshitaka Hamamura, Shinichiro Suganuma, Ayumi Takano, Toshihiko Matsumoto, Haruhiko Shimoyama. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 30.05.2018.

A method for estimating dry forage intake by sheep using polyethylene glycol as a faecal marker measured with NIRS.

PubMed

Hassoun, P; Viudes, G; Autran, P; Bastianelli, D; Bocquier, F

2013-08-01

In experiments based on ruminants' individual dry matter intake (DMI) assessment, several external markers can be used to estimate faecal output when total faeces collection is not possible. However, preparation of the markers to be administered and analytical procedures used for marker content determination are time-consuming thus strongly limiting the number of animals involved in the experiments. In this paper, polyethylene glycol (PEG, molecular weight 6000 da) was tested as a faecal marker. Four trials were conducted on dry, non-lactating ewes kept in digestibility crates that allowed individual measurements. The overall experiment was designed to assess the major factors that could lessen the effectiveness of this method, assuming that the use of grab samples of faeces is sufficient. Trial 1 was designed to test two levels of PEG (20 and 40 g/day) administered in two equal amounts. Trial 2 was designed to test the effect of either a single morning (0800 h) dose (20 g/day) or a twice daily administration (0800 and 1600 h) of the same fractionated dose. Trial 3 was designed to test a 20 g/day dose of PEG administered once daily to ewes fed with hays of different qualities: medium (MH) and low (LH). In trial 4, a lower dose of PEG (10 g/day) was administered once a day to ewes fed with fresh oat-vetch forage. It was demonstrated that PEG could be precisely estimated (average prediction error = 3.47 g/kg) with near-infrared reflectance spectroscopy (NIRS). On the basis of the four trials, it has been proved that PEG administration (20 and 40 g/day) did not significantly affect the DMI of ewes fed dry diets (trials 1, 2 and 3), whereas there was an unexpected increase of DMI for ewes fed exclusively with green feed (trial 4) without DM digestibility modification. Providing PEG as a single dose (0800 h) or split into two equal parts (0800 and 1600 h) did not alter the estimated DMI. Considering the interest of grab sampling, there were clear variations of PEG in faeces with higher concentrations observed at 0800 and 1600 h and lower concentrations at 1400 h. Consequently, with PEG (measured with NIRS) administered once and using the grab sampling procedure (morning collection), it is possible to estimate the DMI of dry feeds with good accuracy. For green feeds, more research is needed as the estimated results are still highly variable.

Side effects from intense pulsed light: Importance of skin pigmentation, fluence level and ultraviolet radiation-A randomized controlled trial.

PubMed

Thaysen-Petersen, Daniel; Erlendsson, Andres M; Nash, J F; Beerwerth, Frank; Philipsen, Peter A; Wulf, Hans C; Paasch, Uwe; Haedersdal, Merete

2017-01-01

Intense pulsed light (IPL) is a mainstream treatment for hair removal. Side effects after IPL are known, but risk factors remain to be investigated. The objective of this study was to assess the contribution of skin pigmentation, fluence level, and ultraviolet radiation (UVR) on IPL-induced side effects. The study was a blinded, randomized intra-individual controlled trial including 16 healthy subjects with Fitzpatrick Skin Types (FST) II-V. Three test areas were each divided into four sites, randomized to a single IPL exposure of 22, 34, 46 J/cm 2 or triple stacking of 46 J/cm 2 . Areas were subsequently randomized to no UVR or single solar-simulated UVR exposure of 3 Standard Erythema Dose at 30 minutes or 24 hours after IPL. Each area had a corresponding control, resulting in 15 treatment sites. Follow-up visits were scheduled up to 4 weeks after IPL. Outcome measures were: (i) blinded clinical skin reactions; (ii) objectively measured erythema and pigmentation; (iii) pain measured by visual analog scale (VAS); (iv) histology (H&E, Fontana-Masson); and (v) mRNA-expression of p53. Fifteen subjects with FST II-IV completed the protocol. IPL induced a wide range of skin reactions, including erythema (87% of subjects), purpura (27%), blisters (20%), edema (13%), crusting (13%), hyper- (60%), and hypopigmentation (20%). Darker skin pigmentation and increasing IPL fluence were determinants for IPL-induced side effects (P ≤ 0.002), while a single exposure of UVR did not exacerbate side effects (P ≥ 0.180). Clinical findings were confirmed objectively by reflectance spectrometry and qualitatively by histological changes in skin architecture, inflammatory infiltration, and pigmentation. Marker of cellular DNA damage, that is, p53, did not increase after IPL (P ≥ 0.24). Skin pigmentation and IPL fluence are major determinants of side effects after IPL exposure, while a single exposure to three SED of UVR at 30 minutes or 24 hours after IPL, does not amplify such side effects. Lasers Surg. Med. 49:88-96, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Low efficacy of mebendazole against hookworm in Vietnam: two randomized controlled trials.

PubMed

Flohr, Carsten; Tuyen, Luc Nguyen; Lewis, Sarah; Minh, Truong Tan; Campbell, Jim; Britton, John; Williams, Hywel; Hien, Tran Tinh; Farrar, Jeremy; Quinnell, Rupert J

2007-04-01

Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010. The treatment used in Vietnam is single dose oral mebendazole (Phardazone) 500 mg. We tested the efficacy of single dose mebendazole 500 mg in the therapy of hookworm infection in a randomized double-blind placebo-controlled trial among 271 Vietnamese schoolchildren. The treatment efficacy of single dose mebendazole in children did not differ significantly from placebo, with a reduction in mean eggs per gram of feces relative to placebo of 31% (95% CI -9 to 56%, P = 0.1). In light of these findings we then carried out a similar randomized trial comparing triple dose mebendazole, single dose albendazole, and triple dose albendazole against placebo in 209 adults in the same area. The estimated reduction in mean post-treatment eggs per gram of feces relative to placebo was 63% (95% CI 30-81%) for triple mebendazole, 75% (47-88%) for single albendazole, and 88% (58-97%) for triple albendazole. Our results suggest that single dose oral mebendazole has low efficacy against hookworm infection in Vietnam, and that it should be replaced by albendazole. These findings are of major public health relevance given the opportunity costs of treating entire populations with ineffective therapies. We recommend that efficacy of anti-helminth therapies is pilot tested before implementation of national gut worm control programs.

Satellite cell response to concurrent resistance exercise and high-intensity interval training in sedentary, overweight/obese, middle-aged individuals.

PubMed

Pugh, Jamie K; Faulkner, Steve H; Turner, Mark C; Nimmo, Myra A

2018-02-01

Sarcopenia can begin from the 4-5th decade of life and is exacerbated by obesity and inactivity. A combination of resistance exercise (RE) and endurance exercise is recommended to combat rising obesity and inactivity levels. However, work continues to elucidate whether interference in adaptive outcomes occur when RE and endurance exercise are performed concurrently. This study examined whether a single bout of concurrent RE and high-intensity interval training (HIIT) alters the satellite cell response following exercise compared to RE alone. Eight sedentary, overweight/obese, middle-aged individuals performed RE only (8 × 8 leg extensions at 70% 1RM), or RE + HIIT (10 × 1 min at 90% HR max on a cycle ergometer). Muscle biopsies were collected from the vastus lateralis before and 96 h after the RE component to determine muscle fiber type-specific total (Pax7 + cells) and active (MyoD + cells) satellite cell number using immunofluorescence microscopy. Type-I-specific Pax7 + (P = 0.001) cell number increased after both exercise trials. Type-I-specific MyoD + (P = 0.001) cell number increased after RE only. However, an elevated baseline value in RE + HIIT compared to RE (P = 0.046) was observed, with no differences between exercise trials at 96 h (P = 0.21). Type-II-specific Pax7 + and MyoD + cell number remained unchanged after both exercise trials (all P ≥ 0.13). Combining a HIIT session after a single bout of RE does not interfere with the increase in type-I-specific total, and possibly active, satellite cell number, compared to RE only. Concurrent RE + HIIT may offer a time-efficient way to maximise the physiological benefits from a single bout of exercise in sedentary, overweight/obese, middle-aged individuals.

Does partial coating with titanium improve the radiographic fusion rate of empty PEEK cages in cervical spine surgery? A comparative analysis of clinical data.

PubMed

Kotsias, Andreas; Mularski, Sven; Kühn, Björn; Hanna, Michael; Suess, Olaf

2017-01-01

Anterior cervical diskectomy and fusion (ACDF) is a well-established surgical treatment. Several types of intervertebral spacers can be used, but there is increasing evidence that PEEK cages yield insufficient fusion and thus less clinical improvement. The study aim was to assess the outcomes of single-level ACDF with an empty PEEK cage partially coated with titanium. This prospective multicenter single-arm clinical study collected follow-up data at 6, 12, and 18 months. A post hoc comparison was made to closely matched patients from another similar trial treated with identically designed, empty, uncoated PEEK cages. There were 49 of 50 patients (98%) who met the MCID of 3+ points of improvement on VAS pain or had an 18-month VAS ≤ 1. Yet even by 18 months post-op, only 40 of 50 (80%) PEEK + Ti patients achieved complete bony fusion. The PEEK + Ti group ( n  = 49) seemed to have somewhat better fusion scores and significantly better pain relief at 6 M than the matched controls ( n  = 49), but these differences did not persist at 12 M or 18 M. Patients (with either implant) who achieved complete bony fusion had significantly better improvement of pain at 6 M and disability at 6 M and 12 M than patients that remained unfused. ACDF is effective treatment for cervical myelopathy and radiculopathy. Although this and other studies show that titanium fuses better, partial coating of a PEEK cage does not improve the fusion rate sufficiently or confer other lasting clinical benefit. PEEK cages fully coated with titanium should be tested in prospective randomized comparative trials. Prospective, multicenter, single-arm clinical observational study without an individual Trial registration number. Study design and post hoc data analysis according to the "PIERCE-PEEK study", ISRCTN42774128, retrospectively registered 14 April 2009.

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.

Positive Association of Vitamin E Supplementation with Hemoglobin Levels in Mildly Anemic Healthy Pakistani Adults.

PubMed

Jilani, Tanveer; Azam, Iqbal; Moiz, Bushra; Mehboobali, Naseema; Perwaiz Iqbal, Mohammad

2015-01-01

Hemoglobin levels slightly below the lower limit of normal are common in adults in the general population in developing countries. A few human studies have suggested the use of antioxidant vitamins in the correction of mild anemia. The objective of the present study was to investigate the association of vitamin E supplementation in mildly anemic healthy adults with post-supplemental blood hemoglobin levels in the general population of Karachi, Pakistan. In a single-blinded and placebo-controlled randomized trial, 124 mildly anemic subjects from the General Practitioners' Clinics and personnel of the Aga Khan University were randomized into intervention (n = 82) and control (n = 42) group. In the intervention group, each subject was given vitamin E (400 mg) everyday for a period of three months, while control group subjects received a placebo. Eighty six subjects completed the trial. Fasting venous blood was collected at baseline and after three months of supplementation. Hemoglobin levels and serum/plasma concentrations of vitamin E, vitamin B12, folate, ferritin, serum transferrin receptor (sTfR), glucose, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, creatinine, total-antioxidant-status and erythropoietin were measured and analyzed using repeated measures ANOVA and multiple linear regression. The adjusted regression coefficients (β) and standard error [SE(β)] of the significant predictors of post-supplemental hemoglobin levels were serum concentration of vitamin E (0.983[0.095]), gender (- 0.656[0.244]), sTfR (- 0.06[0.02]) and baseline hemoglobin levels (0.768[0.077]). The study showed a positive association between vitamin E supplementation and enhanced hemoglobin levels in mildly anemic adults.

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

PubMed Central

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

2009-01-01

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

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

PubMed

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

2010-08-01

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

The efficacy of Australian essential oils for the treatment of head lice infestation in children: A randomised controlled trial.

PubMed

Greive, Kerryn A; Barnes, Tanya M

2018-05-01

The increase in resistance of head lice to neurotoxic pediculicides and public concern over their safety has led to an increase in alternative treatments, many of which are poorly researched or even untested. A multicentre, randomised, assessor-blind, parallel-group trial (Trial 1) was conducted to compare the safety and efficacy of a head lice treatment containing Australian eucalyptus oil and Leptospermum petersonii (EO/LP solution; applied thrice with 7-day intervals between applications) with a neurotoxic treatment containing pyrethrins and piperonyl butoxide (P/PB mousse; applied twice with a 7-day interval) in children. A single-blind, open trial (Trial 2) was conducted to assess the efficacy of EO/LP solution following a single application. In addition, skin irritancy and sensitisation tests using EO/LP solution were performed in adults and children. In vitro tests were performed to further assess the ovicidal and pediculicidal efficacy of EO/LP solution. EO/LP solution was found to be more than twice as effective in curing head lice infestation as P/PB mousse in per-protocol participants (Trial 1; 83% vs 36%, P < 0.0001), and was also found to be 100% pediculicidal following a single application (Trial 2). Adverse events were limited to transient itching, burning or stinging. Further skin testing with the EO/LP solution reported no irritation or sensitisation in adults, or irritation in children. In vitro exposure of lice and eggs to the EO/LP solution resulted in 100% mortality. The efficacy, safety and relative ease of use of the EO/LP solution make it a viable alternative in treating head lice. © 2017 Ego Pharmaceuticals Pty Ltd. Australasian Journal of Dermatology published by John Wiley & Sons, Ltd. on behalf of The Australasian College of Dermatologists.

Duration of treatment for asymptomatic bacteriuria during pregnancy.

PubMed

Widmer, Mariana; Lopez, Ivana; Gülmezoglu, A Metin; Mignini, Luciano; Roganti, Ariel

2015-11-11

A previous Cochrane systematic review has shown that antibiotic drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single-dose therapy is as effective as longer conventional antibiotic treatment. To assess the effects of different durations of treatment for asymptomatic bacteriuria in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015) and reference lists of identified articles. Randomized and quasi-randomized trials comparing antimicrobial therapeutic regimens that differed in duration (particularly comparing single dose with longer duration regimens) in pregnant women diagnosed with asymptomatic bacteriuria. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach. We included 13 studies, involving 1622 women. All were comparisons of single-dose treatment with short-course (four- to seven-day) treatments. The risk of bias of trials included in this review was largely unclear, and most trials were at high risk of performance bias. The quality of the evidence was assessed using the GRADE approach. When the any antibiotic agent was used, the 'no cure' rate for asymptomatic bacteriuria in pregnant women was slightly lower for the short-course treatment over the single-dose treatment, although there was evidence of statistical heterogeneity (average risk ratio (RR) 1.28, 95% confidence interval (CI) 0.87 to 1.88; women = 1502, studies = 13; I² = 56%; very low quality evidence). Data from only good quality trials also showed better cure rates with short (four- to seven-day) regimens of the same microbial agent (average RR 1.72, 95% CI 1.27 to 2.33; women = 803, studies = two; I² = 0%; high quality evidence). There was no clear difference in the recurrence of asymptomatic bacteriuria rate between treatment and control groups, whether the same or different microbial agents were used (RR 1.13, 95% CI 0.77 to 1.66; 445 women studies = eight; I² = 0%; very low quality evidence). Differences were detected for low birthweight babies, favoring a short course (four- to seven-day treatment) of the same microbial agent, although the data come from a single trial (RR 1.65, 95% CI 1.06 to 2.57; 714 women; high quality evidence), but no differences were observed for preterm delivery (RR 1.17, 95% CI 0.77 to 1.78; women = 804; studies = three; I² = 23%; moderate quality) or pyelonephritis (RR 3.09, 95% CI 0.54 to 17.55; women = 102; studies = two; I² = 0%; very low quality evidence). Finally, single-dose treatment of any microbial agent was associated with a decrease in reports of 'any side effects' (RR 0.70, 95% CI 0.56 to 0.88; 1460 women, studies = 12; I² = 9%; low quality evidence). Evidence was downgraded for risk of bias concerns in trials contributing data and for imprecise effect estimates (wide confidence intervals crossing the line of no effect, and in some cases, small studies with few events). A single-dose regimen of antibiotics may be less effective than a short-course (four- to seven-day) regimen, but more evidence is needed from large trials measuring important outcomes, such as cure rate. Women with asymptomatic bacteriuria in pregnancy should be treated by the standard regimen of antibiotics until more data become available testing seven-day treatment compared with shorter courses of three- or five-day regimens.

Local Media Influence on Opting-Out from an Exception from Informed Consent Trial

PubMed Central

Nelson, Maria J; DeIorio, Nicole M; MD, Terri Schmidt; Griffiths, Denise; Daya, Mohamud; Haywood, Liana; Zive, Dana; Newgard, Craig D

2010-01-01

Objectives News media are used for community education and notification in exception from informed consent clinical trials, yet their effectiveness as an added safeguard in such research remains unknown. We assessed the number of callers requesting opt-out bracelets following each local media report and described the errors and content within each media report. Methods We undertook a descriptive analysis of local media trial coverage (newspaper, television, radio, and weblog) and opt-out requests over a 41-month period at a single site participating in an exception from informed consent out-of-hospital trial. Two non-trial investigators independently assessed forty-one content-based media variables (including background, trial information, graphics, errors, publication information, assessment) using a standardized, semi-qualitative data collection tool. Major errors were considered serious misrepresentation of the trial purpose or protocol, whereas minor errors included misinformation unlikely to mislead the lay reader about the trial. We plotted the temporal relationship between opt-out bracelet requests and media reports. Descriptive information about the news sources and the trial coverage are presented. Results We collected 39 trial-related media reports (33 newspaper, 1 television, 1 radio, and 4 blogs). There were thirteen errors in 9 (23%) publications, 7 of which were major and 6 minor. Of 384 requests for 710 bracelets, 310 requests (80%) occurred within 4 days after trial media coverage. Graphical timeline representation of the data suggested a close association between media reports about the trial and requests for opt-out bracelets. Conclusions Based on results from a single site, local media coverage for an exception from informed consent clinical trial had a substantial portion of errors and appeared closely associated with opt-out requests. PMID:19682770

Sensitivity Analysis of Situational Awareness Measures

NASA Technical Reports Server (NTRS)

Shively, R. J.; Davison, H. J.; Burdick, M. D.; Rutkowski, Michael (Technical Monitor)

2000-01-01

A great deal of effort has been invested in attempts to define situational awareness, and subsequently to measure this construct. However, relatively less work has focused on the sensitivity of these measures to manipulations that affect the SA of the pilot. This investigation was designed to manipulate SA and examine the sensitivity of commonly used measures of SA. In this experiment, we tested the most commonly accepted measures of SA: SAGAT, objective performance measures, and SART, against different levels of SA manipulation to determine the sensitivity of such measures in the rotorcraft flight environment. SAGAT is a measure in which the simulation blanks in the middle of a trial and the pilot is asked specific, situation-relevant questions about the state of the aircraft or the objective of a particular maneuver. In this experiment, after the pilot responded verbally to several questions, the trial continued from the point frozen. SART is a post-trial questionnaire that asked for subjective SA ratings from the pilot at certain points in the previous flight. The objective performance measures included: contacts with hazards (power lines and towers) that impeded the flight path, lateral and vertical anticipation of these hazards, response time to detection of other air traffic, and response time until an aberrant fuel gauge was detected. An SA manipulation of the flight environment was chosen that undisputedly affects a pilot's SA-- visibility. Four variations of weather conditions (clear, light rain, haze, and fog) resulted in a different level of visibility for each trial. Pilot SA was measured by either SAGAT or the objective performance measures within each level of visibility. This enabled us to not only determine the sensitivity within a measure, but also between the measures. The SART questionnaire and the NASA-TLX, a measure of workload, were distributed after every trial. Using the newly developed rotorcraft part-task laboratory (RPTL) at NASA Ames Research Center, each pilot flew eight trials, four using SAGAT and four using performance measures. Each set of four trials differed by level of visibility as well. The flight paths were very similar in appearance and hazard number, allowing comparison between flight paths. The pilots were tasked with flying along a road at an assigned altitude and speed while avoiding any hazards that they happened upon. The attempt here was not to find a single best measure of SA, but rather to begin an investigation of the sensitivity of common measures of SA. Upon completion of this study, its results, in combination with future studies, should allow us to develop an empirically based taxonomy of SA measures and the contexts for their appropriate use.

Evaluating effectiveness and cost-effectiveness of a group psychological intervention using cognitive behavioural strategies for women with common mental disorders in conflict-affected rural Pakistan: study protocol for a randomised controlled trial.

PubMed

Chiumento, Anna; Hamdani, Syed Usman; Khan, Muhammad Naseem; Dawson, Katie; Bryant, Richard A; Sijbrandij, Marit; Nazir, Huma; Akhtar, Parveen; Masood, Aqsa; Wang, Duolao; van Ommeren, Mark; Rahman, Atif

2017-04-26

The impact of humanitarian disasters upon mental health is well recognised. The evidence for psychological interventions for mental health is mounting, but few interventions have been rigorously tested in humanitarian settings. To be sustainable in humanitarian settings interventions need to be short, simple, deliverable by nonspecialists under supervision, and adopt a transdiagnostic approach where an array of mental health outcomes are addressed simultaneously. These elements have been incorporated into the newly developed WHO Problem Management Plus (PM+) Group intervention. The aim of this trial is to evaluate the locally adapted PM+ Group intervention for women in Swat, Pakistan. This PM+ Group trial is a two-arm, single-blind, cluster randomised controlled trial conducted in a community-based setting with women in rural Pakistan. PM+ is delivered in partnership with the Lady Health Worker (LHW) Programme which provides community-based health care to women in Pakistan. Thirty-four LHW clusters will be randomised in a 1:1 allocation ratio using a permuted-block randomisation method. Participants screened and found to meet the inclusion criteria will be allocated to either the PM+ intervention group (n = 306), or the control arm (n = 306). The manualised PM+ intervention involves five sessions, each lasting 3 h, and introduces four strategies applied by participants to problems that they are facing. It is delivered by local female facilitators with a minimum of 16 years of education who are provided with targeted training and supervision. The primary outcome is individual psychological distress, measured by levels of anxiety and depression on the Hospital Anxiety and Depression Scale at 20 weeks after baseline. Secondary outcomes include major depression, post-traumatic stress disorder, levels of social support, levels of functioning, and economic effectiveness. Intervention acceptability will be explored through an embedded qualitative study. The PM+ Group trial will provide important evidence on the effectiveness of an empirically supported psychological treatment delivered by nonspecialists in a humanitarian setting. If proven effective, the qualitative component will inform strategies for PM+ Group scale-up in health systems in other humanitarian settings. Australian New Zealand Clinical Trials Registry, identifier: ACTRN12616000037404. Registered on 19 January 2016; WHO Protocol ID RPC705, v.4, 2 November 2015.

Long-term effect of smartphone-delivered Interval Walking Training on physical activity in patients with type 2 diabetes: protocol for a parallel group single-blinded randomised controlled trial

PubMed Central

Ried-Larsen, Mathias; Karstoft, Kristian; Brinkløv, Cecilie Fau; Brøns, Charlotte; Nielsen, Rasmus Oestergaard; Nielsen, Jens Steen; Vaag, Allan Arthur; Pedersen, Bente Klarlund; Langberg, Henning

2017-01-01

Introduction Physical activity is a cornerstone in type 2 diabetes (T2D) rehabilitation. Effective long-term and low-cost strategies to keep these patients' physically active are needed. However, maintaining physical activity behaviour is difficult once formalised interventions end. Structured exercise training supported by mobile technology and remote feedback is potentially an effective strategy. The objective of the trial is to investigate whether mobile health support using the InterWalk application for smartphones is effective in increasing physical activity levels in persons with T2D over time compared with standard care. We investigate whether Interval Walking Training using the InterWalk application is superior to Danish municipality-based rehabilitation in increasing moderate-and-vigorous physical activity levels in patients with T2D across 52 weeks. Secondary, we hypothesise that a motivational programme added from end of intervention to 52 weeks further increases level of physical activity in everyday life in patients with T2D. Methods and analysis The trial is a parallel-group, open-labelled, randomised controlled trial with long-term follow-up at 52 week including patients with T2D. The primary outcome is change in moderate-and-vigorous physical activity. The key secondary outcome includes motivation for physical activity behaviour change. Other secondary outcomes are VO2-peak, strength in the lower extremities. Exclusion criterion is medical contraindication to exercise. We include up to 246 patients and randomly allocate them into a control (standard group) or an experimental group (8–12 weeks of IWT supported by the smartphone-based InterWalk application) in a 1:2 fashion. After intervention, the experimental group is randomly allocated into two follow-up conditions with unsupervised IWT with or without motivational support until 52-week follow-up. The intention-to-treat principle is applied. Ethics and dissemination The local regional Research Ethics Committee in Denmark (H-1-2014-074) and the Danish Data Protection Agency (j.nr. 2014-54-0897) have approved the trial. Positive, negative or inconclusive results will be disseminated in scientific journals and conferences. Trial registration number NCT02341690. PMID:28389489

Attrition during a randomized controlled trial of reduced nicotine content cigarettes as a proxy for understanding acceptability of nicotine product standards

PubMed Central

Mercincavage, Melissa; Wileyto, E. Paul; Saddleson, Megan L.; Lochbuehler, Kirsten; Donny, Eric C.; Strasser, Andrew A.

2017-01-01

Aims To determine (1) if nicotine content affects study attrition – a potential behavioral measure of acceptability – in a trial that required compliance with three levels of reduced nicotine content (RNC) cigarettes, and (2) if attrition is associated with subjective and behavioral responses to RNC cigarettes. Design Secondary analysis of a 35-day, parallel design, open-label, randomized controlled trial. After a 5-day baseline period, participants were randomized to smoke for three, 10-day periods: their preferred brand (control group), or RNC cigarettes with three nicotine levels in a within-subject, stepdown (1 group: high-moderate-low) or non-stepdown (5 groups: high-low-moderate, low-moderate-high, low-high-moderate, moderate-low-high, moderate-high-low) fashion. Setting A single site in Philadelphia, Pennsylvania, USA. Participants 246 non-treatment-seeking daily smokers (M age = 39.52, CPD = 20.95, 68.3% White) were recruited from October 2007 to June 2013. Measurements The primary outcome was attrition. Key predictors were nicotine content transition and study period. Exploratory predictors were taste and strength subjective ratings, total puff volume, and carbon monoxide (CO) boost. Covariates included: age, gender, race, education, and nicotine dependence. Findings Overall attrition was 31.3% (n = 77): 24.1% of the control and 25.0% of the stepdown RNC cigarette groups dropped out vs. 44.6% of non-stepdown groups (p = 0.006). Compared with controls, attrition odds were 4.5 and 4.7 times greater among smokers transitioning from preferred and the highest RNC cigarettes to the lowest RNC cigarettes, respectively (p’s = .001 and .003). Providing more favorable initial taste ratings of study cigarettes decreased attrition odds by 2% (p = .012). Conclusions The majority of participants completed a 35-day trial of varying levels of reduced nicotine content cigarettes. Participant drop-out was greater for cigarettes with lower nicotine content and less in smokers reporting more favorable subjective ratings of the cigarettes. PMID:28107596

ECL-IAA and ECL-GADA Can Identify High-Risk Single Autoantibody-Positive Relatives in the TrialNet Pathway to Prevention Study.

PubMed

Steck, Andrea K; Fouts, Alexandra; Miao, Dongmei; Zhao, Zhiyuan; Dong, Fran; Sosenko, Jay; Gottlieb, Peter; Rewers, Marian J; Yu, Liping

2016-07-01

Relatives with single positive islet autoantibodies have a much lower risk of progression to diabetes than those with multiple autoantibodies. TrialNet subjects positive for single autoantibody to insulin (mIAA) (n = 50) or single autoantibody to glutamic acid decarboxylase (GADA) (n = 50) were analyzed using new electrochemiluminescence (ECL) assays (ECL-IAA and ECL-GADA, respectively) at their initial visit and longitudinally over time. Affinity assays were performed on a subset of single autoantibody-positive subjects at initial and most recent visits. After a mean follow-up of 5.3 years, 20 subjects developed type 1 diabetes. Among either single GADA or single mIAA subjects, those who were positive in the ECL assay showed higher affinity at the initial visit, and affinity results stayed consistent over time. No converting events from low to high or high to low affinity were seen over time. Confirmed positivity for ECL is associated with high affinity and can help staging of risk for type 1 diabetes in single autoantibody-positive subjects.

Single-Trial Analysis of Inter-Beat Interval Perturbations Accompanying Single-Switch Scanning: Case Series of Three Children With Severe Spastic Quadriplegic Cerebral Palsy.

PubMed

Leung, Brian; Chau, Tom

2016-02-01

Single-switch access in conjunction with scanning remains a fundamental solution in restoring communication for many children with profound physical disabilities. However, untimely switch inaction and unintentional switch activations can lead to user frustration and impede functional communication. A previous preliminary study, in the context of a case series with three single-switch users, reported that correct, accidental and missed switch activations could elicit cardiac deceleration and increased phasic skin conductance on average, while deliberate switch non-use was associated with autonomic nonresponse. The present study investigated the possibility of using blood volume pulse recordings from the same three pediatric single-switch users to track the aforementioned switch events on a single-trial basis. Peaks of the line length time series derived from the empirical mode decomposition of the inter-beat interval time series matched, on average, a high percentage (above 80%) of single-switch events, while unmatched peaks coincided moderately (below 37%) with idle time during scanning. These results encourage further study of autonomic measures as complementary information channels to enhance single-switch access.

Exploration of computational methods for classification of movement intention during human voluntary movement from single trial EEG.

PubMed

Bai, Ou; Lin, Peter; Vorbach, Sherry; Li, Jiang; Furlani, Steve; Hallett, Mark

2007-12-01

To explore effective combinations of computational methods for the prediction of movement intention preceding the production of self-paced right and left hand movements from single trial scalp electroencephalogram (EEG). Twelve naïve subjects performed self-paced movements consisting of three key strokes with either hand. EEG was recorded from 128 channels. The exploration was performed offline on single trial EEG data. We proposed that a successful computational procedure for classification would consist of spatial filtering, temporal filtering, feature selection, and pattern classification. A systematic investigation was performed with combinations of spatial filtering using principal component analysis (PCA), independent component analysis (ICA), common spatial patterns analysis (CSP), and surface Laplacian derivation (SLD); temporal filtering using power spectral density estimation (PSD) and discrete wavelet transform (DWT); pattern classification using linear Mahalanobis distance classifier (LMD), quadratic Mahalanobis distance classifier (QMD), Bayesian classifier (BSC), multi-layer perceptron neural network (MLP), probabilistic neural network (PNN), and support vector machine (SVM). A robust multivariate feature selection strategy using a genetic algorithm was employed. The combinations of spatial filtering using ICA and SLD, temporal filtering using PSD and DWT, and classification methods using LMD, QMD, BSC and SVM provided higher performance than those of other combinations. Utilizing one of the better combinations of ICA, PSD and SVM, the discrimination accuracy was as high as 75%. Further feature analysis showed that beta band EEG activity of the channels over right sensorimotor cortex was most appropriate for discrimination of right and left hand movement intention. Effective combinations of computational methods provide possible classification of human movement intention from single trial EEG. Such a method could be the basis for a potential brain-computer interface based on human natural movement, which might reduce the requirement of long-term training. Effective combinations of computational methods can classify human movement intention from single trial EEG with reasonable accuracy.

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

PubMed

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

2015-11-01

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

A 1-year trial of repeated high-dose intravenous iron isomaltoside 1000 to maintain stable hemoglobin levels in inflammatory bowel disease.

PubMed

Reinisch, Walter; Altorjay, Istvan; Zsigmond, Ferenc; Primas, Christian; Vogelsang, Harald; Novacek, Gottfried; Reinisch, Sieglinde; Thomsen, Lars L

2015-01-01

Iron isomaltoside 1000 (Monofer®) is a high-dose intravenous (IV) iron, which in a recent 8 weeks trial in inflammatory bowel disease (IBD) subjects with iron deficiency anemia (IDA) demonstrated good tolerability and efficacy. The present trial is an extension to this trial, which evaluates the need for additional high IV iron doses to maintain a stable hemoglobin (Hb) ≥12.0 g/dl. This was a prospective, open-label, 12 months trial of European IBD subjects willing to participate after completing the lead-in trial. Subjects were allowed re-dosing with 500-2000 mg single doses of iron isomaltoside 1000 infused over ∼15 min at 3 months intervals depending on a predefined algorithm. Outcome measures included Hb, safety parameters and need for additional iron dosing. A total of 39 subjects were enrolled of which 34 subjects required re-dosing with a median cumulative 1-year dose of 1.8 g (mean cumulative dose 2.2 g). The mean (SD) Hb was 12.3 (1.5) g/dl at baseline, 12.8 (1.6) g/dl at 3 months, 12.8 (1.6) g/dl at 6 months, 12.9 (1.4) g/dl at 9 months and 12.9 (1.6) g/dl at 12 months. Seventy-four percent of subjects who had an Hb ≥12.0 g/dl at baseline were able to maintain Hb ≥12.0 g/dl till the end of the trial at 12 months. Nonserious probably related hypersensitivity reactions without significant hypotension were reported at the beginning of the infusion in two subjects, who recovered without sequelae. Repeated treatment of iron deficiency with iron isomaltoside 1000 could avoid episodes of IDA without major safety issues.

The Acute and Residual Effect of a Single Exercise Session on Meal Glucose Tolerance in Sedentary Young Adults

PubMed Central

Short, Kevin R.; Pratt, Lauren V.; Teague, April M.

2012-01-01

The study goals were to (1) establish the variability in postprandial glucose control in healthy young people consuming a mixed meal and, then (2) determine the acute and residual impact of a single exercise bout on postprandial glucose control. In study 1, 18 people completed two similar mixed meal trials and an intravenous glucose tolerance test (IVGTT). There were strong test-retest correlations for the post-meal area under the curve (AUC) for glucose, insulin, and Cpeptide (r = 0.73–0.83) and the Matsuda insulin sensitivity index (ISI, r = 0.76), and between meal and IVGTT-derived ISI (r = 0.83). In study 2, 11 untrained young adults completed 3 trials. One trial (No Ex) was completed after refraining from vigorous activity for ≥3 days. On the other 2 trials, a 45-min aerobic exercise bout was performed either 17-hours (Prior Day Ex) or 1-hour (Same Day Ex) before consuming the test meal. Compared to No Ex and Prior Day Ex, which did not differ from one another, there were lower AUCs on the Same Day Ex trial for glucose (6%), insulin (20%) and C-peptide (14%). Thus, a single moderate intensity exercise session can acutely improve glycemic control but the effect is modest and short-lived. PMID:22666560

Executive Control Over Cognition: Stronger and Earlier Rule-Based Modulation of Spatial Category Signals in Prefrontal Cortex Relative to Parietal Cortex

PubMed Central

Goodwin, Shikha J.; Blackman, Rachael K.; Sakellaridi, Sofia

2012-01-01

Human cognition is characterized by flexibility, the ability to select not only which action but which cognitive process to engage to best achieve the current behavioral objective. The ability to tailor information processing in the brain to rules, goals, or context is typically referred to as executive control, and although there is consensus that prefrontal cortex is importantly involved, at present we have an incomplete understanding of how computational flexibility is implemented at the level of prefrontal neurons and networks. To better understand the neural mechanisms of computational flexibility, we simultaneously recorded the electrical activity of groups of single neurons within prefrontal and posterior parietal cortex of monkeys performing a task that required executive control of spatial cognitive processing. In this task, monkeys applied different spatial categorization rules to reassign the same set of visual stimuli to alternative categories on a trial-by-trial basis. We found that single neurons were activated to represent spatially defined categories in a manner that was rule dependent, providing a physiological signature of a cognitive process that was implemented under executive control. We found also that neural signals coding rule-dependent categories were distributed between the parietal and prefrontal cortex—however, not equally. Rule-dependent category signals were stronger, more powerfully modulated by the rule, and earlier to emerge in prefrontal cortex relative to parietal cortex. This suggests that prefrontal cortex may initiate the switch in neural representation at a network level that is important for computational flexibility. PMID:22399773

Field trial of solvent-free emulsion in Oregon : appendices.

DOT National Transportation Integrated Search

2003-03-01

This final report summarizes construction, laboratory and performance information gathered by ODOT personnel from a single field trial of solvent-free emulsion mix constructed in June 2001. The solvent-free emulsion mix presented several placement pr...

Photobiomodulation therapy (PBMT) and/or cryotherapy in skeletal muscle restitution, what is better? A randomized, double-blinded, placebo-controlled clinical trial.

PubMed

de Paiva, Paulo Roberto Vicente; Tomazoni, Shaiane Silva; Johnson, Douglas Scott; Vanin, Adriane Aver; Albuquerque-Pontes, Gianna Móes; Machado, Caroline Dos Santos Monteiro; Casalechi, Heliodora Leão; de Carvalho, Paulo de Tarso Camillo; Leal-Junior, Ernesto Cesar Pinto

2016-12-01

Cryotherapy for post-exercise recovery remains widely used despite the lack of quality evidence. Photobiomodulation therapy (PBMT) studies (with both low-level laser therapy and light-emitting diode therapy) have demonstrated positive scientific evidence to suggest its use. The study aims to evaluate PBMT and cryotherapy as a single or combined treatment on skeletal muscle recovery after eccentric contractions of knee extensors. Fifty healthy male volunteers were recruited and randomized into five groups (PBMT, cryotherapy, cryotherapy + PBMT, PMBT + cryotherapy, or placebo) for a randomized, double-blinded, placebo-controlled trial that evaluated exercise performance (maximum voluntary contraction (MVC)), delayed onset muscle soreness (DOMS), and muscle damage (creatine kinase (CK)). Assessments were performed at baseline; immediately after; and at 1, 24, 48, 72, and 96 h. Comparator treatments was performed 3 min after exercise and repeated at 24, 48, and 72 h. PBMT was applied employing a cordless, portable GameDay ™ device (combination of 905 nm super-pulsed laser and 875- and 640-nm light-emitting diodes (LEDs); manufactured by Multi Radiance Medical ™ , Solon - OH, USA), and cryotherapy by flexible rubber ice packs. PBMT alone was optimal for post-exercise recovery with improved MVC, decreased DOMS, and CK activity (p < 0.05) from 24 to 96 h compared to placebo, cryotherapy, and cryotherapy + PBMT. In the PBMT + cryotherapy group, the effect of PBMT was decreased (p > 0.05) but demonstrated significant improvement in MVC, decreased DOMS, and CK activity (p < 0.05). Cryotherapy as single treatment and cryotherapy + PBMT were similar to placebo (p > 0.05). We conclude that PBMT used as single treatment is the best modality for enhancement of post-exercise restitution, leading to complete recovery to baseline levels from 24 h after high-intensity eccentric contractions.

AccrualNet: Addressing Low Accrual Via a Knowledge-Based, Community of Practice Platform

PubMed Central

Massett, Holly A.; Parreco, Linda K.; Padberg, Rose Mary; Richmond, Ellen S.; Rienzo, Marie E.; Leonard, Colleen E. Ryan; Quesenbery, Whitney; Killiam, H. William; Johnson, Lenora E.; Dilts, David M.

2011-01-01

Purpose: Present the design and initial evaluation of a unique, Web-enabled platform for the development of a community of practice around issues of oncology clinical trial accrual. Methods: The National Cancer Institute (NCI) conducted research with oncology professionals to identify unmet clinical trial accrual needs in the field. In response, a comprehensive platform for accrual resources, AccrualNet, was created by using an agile development process, storyboarding, and user testing. Literature and resource searches identified relevant content to populate the site. Descriptive statistics were tracked for resource and site usage. Use cases were defined to support implementation. Results: AccrualNet has five levels: (1) clinical trial macrostages (prestudy, active study, and poststudy); (2) substages (developing a protocol, selecting a trial, preparing to open, enrolling patients, managing the trial, retaining participants, and lessons learned); (3) strategies for each substage; (4) multiple activities for each strategy; and (5) multiple resources for each activity. Since its launch, AccrualNet has had more than 45,000 page views, with the Tools & Resources, Conversations, and Training sections being the most viewed. Total resources have increased 69%, to 496 items. Analysis of articles in the site reveals that 22% are from two journals and 46% of the journals supplied a single article. To date, there are 29 conversations with 43 posts. Four use cases are discussed. Conclusion: AccrualNet represents a unique, centralized comprehensive-solution platform to systematically capture accrual knowledge for all stages of a clinical trial. It is designed to foster a community of practice by encouraging users to share additional strategies, resources, and ideas. PMID:22379429

AccrualNet: Addressing Low Accrual Via a Knowledge-Based, Community of Practice Platform.

PubMed

Massett, Holly A; Parreco, Linda K; Padberg, Rose Mary; Richmond, Ellen S; Rienzo, Marie E; Leonard, Colleen E Ryan; Quesenbery, Whitney; Killiam, H William; Johnson, Lenora E; Dilts, David M

2011-11-01

Present the design and initial evaluation of a unique, Web-enabled platform for the development of a community of practice around issues of oncology clinical trial accrual. The National Cancer Institute (NCI) conducted research with oncology professionals to identify unmet clinical trial accrual needs in the field. In response, a comprehensive platform for accrual resources, AccrualNet, was created by using an agile development process, storyboarding, and user testing. Literature and resource searches identified relevant content to populate the site. Descriptive statistics were tracked for resource and site usage. Use cases were defined to support implementation. ACCRUALNET HAS FIVE LEVELS: (1) clinical trial macrostages (prestudy, active study, and poststudy); (2) substages (developing a protocol, selecting a trial, preparing to open, enrolling patients, managing the trial, retaining participants, and lessons learned); (3) strategies for each substage; (4) multiple activities for each strategy; and (5) multiple resources for each activity. Since its launch, AccrualNet has had more than 45,000 page views, with the Tools & Resources, Conversations, and Training sections being the most viewed. Total resources have increased 69%, to 496 items. Analysis of articles in the site reveals that 22% are from two journals and 46% of the journals supplied a single article. To date, there are 29 conversations with 43 posts. Four use cases are discussed. AccrualNet represents a unique, centralized comprehensive-solution platform to systematically capture accrual knowledge for all stages of a clinical trial. It is designed to foster a community of practice by encouraging users to share additional strategies, resources, and ideas.

Nintendo Wii™ Versus Xbox Kinect™ for Assisting People With Parkinson's Disease.

PubMed

Alves, Melissa L M; Mesquita, Beatriz S; Morais, Wenderson S; Leal, Josevan C; Satler, Corina E; Dos Santos Mendes, Felipe A

2018-06-01

This study investigated changes in motor and cognitive skills, anxiety levels, and quality of life perception among patients with Parkinson's Disease (PD) following training with different commercial gaming devices-Nintendo Wii™ and Xbox Kinect™. We used a quasi-experimental, simple blinded clinical trial, dividing 27 patients with PD into three equal groups of nine members: (a) Nintendo Wii™, (b) Xbox Kinect™, and (c) control group. After pretests, experimental group participants spent 10 sessions playing four games of the selected gaming device, while control group participants received no intervention. Only those engaged with the Nintendo Wii™ significantly improved their performance on single and dual task gait tests, decreased anxiety levels, and improved memory, attention, and reversibility. The control group showed no changes on any measures.

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults.

PubMed

Hall, Deborah A; Haider, Haula; Szczepek, Agnieszka J; Lau, Pia; Rabau, Sarah; Jones-Diette, Julie; Londero, Alain; Edvall, Niklas K; Cederroth, Christopher R; Mielczarek, Marzena; Fuller, Thomas; Batuecas-Caletrio, Angel; Brueggemen, Petra; Thompson, Dean M; Norena, Arnaud; Cima, Rilana F F; Mehta, Rajnikant L; Mazurek, Birgit

2016-06-01

There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

Evaluation of a hospital-based day-structuring exercise programme on exacerbated behavioural and psychological symptoms in dementia--the exercise carrousel: study protocol for a randomised controlled trial.

PubMed

Fleiner, Tim; Zijlstra, Wiebren; Dauth, Hannah; Haussermann, Peter

2015-05-26

Conceptual reviews and observational studies describe a link between physical inactivity and behavioural disturbances in people with dementia. Consequently, treatment of these symptoms requires physical activation and pharmacological or physical immobilization should be avoided. The few trials that have been conducted in inpatient dementia care to investigate the effects of exercise on behavioural and psychological symptoms revealed inconsistent results. Due to a lack of evidence, there is a paucity of recommendations for physical activation in this stage of care. Therefore, this trial seeks to investigate the effects of a day-structuring exercise programme on behavioural and psychological symptoms as well as on circadian rhythms of patients with dementia, hospitalized because of their behavioural and psychological disturbances. A single-centre randomised controlled trial will be conducted in three special dementia care units of an old age psychiatry hospital. Enrolled patients will receive either a 2-week exercise programme, or a 2-week social stimulation programme in addition to usual care. Due to the provision of four day-structuring exercise-sessions in the course of an intervention day, the exercise programme for the study group is called exercise-carrousel. Baseline and post-intervention assessment for the primary outcome variable - the overall effects on behavioural and psychological symptoms--will be measured by the Alzheimer's disease Cooperative Study-Clinical Global Impression of Change. The following objectives are set up as secondary outcomes: dimensions of the behavioural and psychological symptoms of dementia (BPSD) and caregiver burden, routine and on-demand psychotropic medication, patients' motor behaviour, diurnal cortisol-levels from saliva probes and brain-derived neurotrophic factor-levels from blood serum. In order to be regarded as an important treatment option for behavioural and psychological symptoms, physical activation in inpatient hospital dementia care requires more evidence and appropriate recommendations. Respecting hospital routines and the intra-daily variability of the patients' motivation and behavioural disturbances in the provision of exercise sessions could lead to higher exercise adherence and better effects on patients' behavioural and psychological symptoms than former trials have presented. The concealment of allocation throughout the trial and the rating of individual exercise exertion present the key challenges and main limitations of this trial. DRKS00006740 (German Clinical Trial Register, date of registration: 28 October 2014).

Irie Classroom Toolbox: a study protocol for a cluster-randomised trial of a universal violence prevention programme in Jamaican preschools

PubMed Central

Baker-Henningham, Helen; Vera-Hernández, Marcos; Alderman, Harold; Walker, Susan

2016-01-01

Introduction We aim to determine the effectiveness of a school-based violence prevention programme implemented in Jamaican preschools, on reducing the levels of aggression among children at school, and violence against children by teachers. Methods and analysis This is a 2-arm, single-blind, cluster-randomised controlled trial with parallel assignment. Clusters are 76 preschools in Kingston, and all teachers and classrooms in the selected schools are included in the study. In addition, a random sample of up to 12 children in the 4-year-old classes have been selected for evaluation of child-level outcomes. The intervention involves training teachers in classroom behaviour management and in strategies to promote children's social-emotional competence. Training is delivered through five full-day workshops, monthly in-class coaching over 2 school terms, and weekly text messages. The primary outcome measures are: (1) observed levels of child aggression and (2) observed violence against children by teachers. Secondary outcomes include observations of the levels of children's prosocial behaviour and the quality of the classroom environment, teachers’ reports of their mental health, teacher-reported child mental health, direct tests of children's self-regulation and child attendance. Ethics and dissemination If this intervention were effective at improving the caregiving environment of young children in school, this would have significant implications for the prevention of child mental health problems, and prevention of violence against children in low and middle-income countries where services are often limited. The intervention is integrated into the school system and involves training existing staff, and thus, represents an appropriate strategy for large-scale implementation and benefits at the population level. Ethical consent for the study was given by the School of Psychology Ethics and Research Committee, Bangor University (ref: 2014-14167), and by the University of the West Indies Ethics Committee (ref: ECP 50,14/15). Trial registration number ISRCTN11968472; Pre-results. PMID:27165651

Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials.

PubMed

Serebruany, Victor L; Glassman, Alexander H; Malinin, Alex I; Sane, David C; Finkel, Mitchell S; Krishnan, Ranga R; Atar, Dan; Lekht, Vladimir; O'Connor, Christopher M

2003-09-01

Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective analysis of the data from several clinical trials reveals that clinical depression is associated with enhanced activation of platelet/endothelial biomarkers even above the level expected in ACS. These findings may contribute to the unfavorable outcome associated with clinical depression in patients with ACS.

Full-Scale Incineration System Trial Burns at the Naval Construction Battalion Center, Gulfport, Mississippi. Volume 2, Part 2

DTIC Science & Technology

1991-07-01

The prime mover for the MWP-2000 is a single steam powered jet venturi scrubber that was manufactured by Hydrosonics, Inc. to develop a negative...orime mover for the MWP-2000 is a single steam powered jet venturi scrubber that was manufactured by Hydrosonics, inc. to develop a negative pressure...packed tower and the scrubber during the trial burn or opening of the TRV, you should include these AWISOs since these shut offs would normally be

Envelope Responses in Single-trial EEG Indicate Attended Speaker in a Cocktail Party

DTIC Science & Technology

2014-06-25

attention at the cued location, which may not produce strong lateralization in alpha power. In fact, a similar cocktail party study found that alpha...enhances selective speech envelope tracking in auditory cortex at a ‘ cocktail party ’ J. Neurosci. 33 1417–26 [9] Cherry E C 1953 Some experiments on the...Envelope responses in single-trial EEG indicate attended speaker in a ‘ cocktail party ’ Cort Horton1, Ramesh Srinivasan1,2 and Michael D’Zmura1

Pyridostigmine in the treatment of orthostatic intolerance.

PubMed

Gales, Barry J; Gales, Mark A

2007-02-01

To review the efficacy of pyridostigmine bromide for the treatment of orthostatic intolerance. MEDLINE and International Pharmaceutical Abstracts were searched (1966-December 2006) using the terms pyridostigmine, acetylcholinesterase inhibitor, orthostatic intolerance, orthostatic hypotension, neurogenic orthostatic hypotension, postural tachycardia syndrome, tachycardia, and orthostatic tachycardia. Pertinent English-language human clinical trials, case reports, and background material were evaluated for safety and efficacy data. The references of reviewed articles were reviewed and used to identify additional sources. Pyridostigmine bromide has been associated with improved baroreceptor sensitivity and presents a novel approach to treatment of orthostatic intolerance. Four single-dose trials and a follow-up survey encompassing a total of 106 patients were identified. One open-label and one placebo-controlled single-dose trial in patients with neurogenic orthostatic hypotension (NOH) found statistically significant improvement in standing diastolic blood pressures (DBP). Absolute improvements in standing DBP were 3.7 and 6.4 mm Hg in the open-label and controlled trials, respectively. Long-term data consist of a single survey of patients receiving open-label pyridostigmine bromide. Twenty-nine percent of patients who initiated maintenance pyridostigmine bromide discontinued therapy. Concomitant NOH medications were taken by 75% of patients, and 85% of patients reported receiving benefit from pyridostigmine bromide. When evaluated for postural tachycardia syndrome, pyridostigmine bromide significantly reduced standing heart rate (10%). Pyridostigmine bromide significantly reduced symptom scores when compared with baseline but not placebo. The majority of patients included in these trials did not have supine hypertension. Single doses of pyridostigmine bromide produced modest but statistically significant improvements in hemodynamic measurements. At this time, long-term data are insufficient to support recommending the routine use of pyridostigmine bromide for treatment of orthostatic intolerance.

Pharmacokinetic properties of BAY 81-8973, a full-length recombinant factor VIII.

PubMed

Shah, A; Delesen, H; Garger, S; Lalezari, S

2015-11-01

BAY 81-8973 is a full-length recombinant factor VIII (FVIII) with the same primary amino acid sequence as sucrose-formulated recombinant FVIII (rFVIII-FS) but is produced with advanced manufacturing technologies. To analyse the pharmacokinetics (PK) of BAY 81-8973 after single and multiple dosing across different age and ethnic groups in the LEOPOLD clinical trial programme. The LEOPOLD trials enrolled patients with severe haemophilia A aged 12-65 years (LEOPOLD I and II) or ≤12 years (LEOPOLD Kids) with ≥150 (LEOPOLD I and II) or ≥50 (LEOPOLD Kids) exposure days to any FVIII product and no history of FVIII inhibitors. PK were assessed using chromogenic and one-stage assays (only chromogenic assay for LEOPOLD Kids) after a single 50-IU kg(-1) dose of BAY 81-8973 and, in a subset of patients in LEOPOLD I, after repeated dosing. Pharmacokinetic analyses were also performed based on age (18 to 65, 12 to <18, 6 to <12 and <6 years) and ethnicity (Asian and non-Asian). Pharmacokinetic assessments in the LEOPOLD I trial showed non-inferiority of BAY 81-8973 vs. rFVIII-FS. The PK of BAY 81-8973 were comparable after single and multiple dosing. Age-based analysis in the three trials showed that plasma concentrations were slightly lower for children, but similar for adolescents compared with adults. Pharmacokinetic results were similar in the different ethnic groups. Results of the LEOPOLD trials show that the BAY 81-8973 pharmacokinetic profile is non-inferior to rFVIII-FS. Similar BAY 81-8973 pharmacokinetic values were observed following single and repeated dosing and across ethnic groups. © 2015 John Wiley & Sons Ltd.

Double gloving to reduce surgical cross-infection.

PubMed

Tanner, J; Parkinson, H

2002-01-01

The invasive nature of surgery, with its increased exposure to blood, means that during surgery there is a high risk of transfer of pathogens. Pathogens can be transferred through contact between surgical patients and the surgical team, resulting in post-operative or blood borne infections in patients or blood borne infections in the surgical team. Both patients and the surgical team need to be protected from this risk. This risk can be reduced by implementing protective barriers such as wearing surgical gloves. Wearing two pairs of surgical gloves, as opposed to one pair, is considered to provide an additional barrier and further reduce the risk of contamination. The primary objective of this review was to determine if double gloving (wearing two pairs of gloves), rather than single gloving, reduces the number of post-operative or blood borne infections in surgical patients or blood borne infections in the surgical team. The secondary objective of this review was to determine if double gloving, rather than single gloving, reduces the number of perforations to the innermost pair of surgical gloves. The innermost gloves (next to skin) compared with the outermost gloves are considered to be the last barrier between the patient and the surgical team. The reviewers searched the Cochrane Wounds Group Specialised Trials Register, MEDLINE, CINAHL, EMBASE and the Cochrane Controlled Trials Register. Glove manufacturing companies and professional organisations were also contacted. Randomised controlled trials involving: single gloving, double gloving, glove liners or coloured puncture indicator systems. Both reviewers independently assessed the relevance and quality of each trial. Trials to be included were cross checked and authenticated by both reviewers. Data was extracted by one reviewer and cross checked for accuracy by the second reviewer. Two trials were found which addressed the primary outcome. A total of 18 randomised controlled trials which measured glove perforations were identified and included in the review. DOUBLE GLOVING (wearing two pairs of latex gloves). Nine trials compared single latex gloves versus double latex gloves. These found no difference in the number of perforations between the single latex gloves and the outermost pair of the double latex gloves, but the number of perforations to the double latex-innermost glove was significantly reduced when two pairs of latex gloves were worn. ORTHOPAEDIC GLOVES (thicker than standard latex gloves). One trial compared single latex orthopaedic gloves with double latex gloves. This showed there was no difference in the number of perforations to the innermost gloves when wearing double latex gloves compared with a single pair of latex orthopaedic gloves. INDICATOR GLOVES (coloured latex gloves worn underneath latex gloves). Three trials compared double latex gloves versus double latex indicator gloves. These trials showed similar numbers of perforations to both the innermost and the outermost gloves for both gloving groups. Perforations to the outermost gloves were detected more easily when double latex indicator gloves were worn. Wearing double latex indicator gloves did not increase the detection of perforations to the innermost gloves. GLOVE LINERS (an insert worn between two pairs of latex gloves). Two trials compared double latex gloves versus double latex gloves with liners. These trials showed a significant reduction in the number of perforations to the innermost glove when a glove liner was worn between two pairs of latex gloves. CLOTH GLOVES (cloth gloves worn on top of latex gloves). Two trials compared double latex gloves versus latex inner with cloth outer gloves. These trials showed that wearing a cloth outer glove significantly reduced the number of perforations to the innermost latex glove. STEEL WEAVE GLOVES (steel weave gloves worn on top of latex gloves). One trial compared double latex gloves versus latex inner with steel weave outer gloves. This trial showed no reduction in the number of perforations to the innermost glove when wearing a steel weave outer glove. Wearing two pairs of latex gloves significantly reduces the number of perforations to the innermost glove. This evidence comes from trials undertaken in 'low risk' surgical specialties, that is specialties which did not include orthopaedic joint surgery. Wearing two pairs of latex gloves does not cause the glove wearer to sustain more perforations to their outermost glove. Wearing double latex indicator gloves enables the glove wearer to detect perforations to the outermost glove more easily than when wearing double latex gloves. However wearing a double latex indicator system will not assist with the detection of perforations to the innermost glove, nor reduce the number of perforations to either the outermost or the innermost glove. Wearing a glove liner between two pairs of latex gloves to undertake joint replacement surgery significantly reduces the number of perforations to the innermost glove compared with double latex gloves only. Wearing cloth outer gloves to undertake joint replacement surgery significantly reduces the number of perforations to the innermost glove compared with wearing double latex gloves. Wearing steel weave outer gloves to undertake joint replacement surgery does not reduce the number of perforations to innermost gloves compared with double latex gloves.

Surrogate endpoints for overall survival in lung cancer trials: a review.

PubMed

Fiteni, Frédéric; Westeel, Virginie; Bonnetain, Franck

2017-05-01

Intermediate endpoints are often used as primary endpoints instead of overall survival (OS) in lung cancer trials but they are not systematically validated as surrogate endpoints for OS. Areas covered: The aim of the study was to review the studies which assessed potential surrogate endpoints for OS in lung cancer trials. Expert commentary: Twenty studies were identified. In operable non-small cell lung cancer (NSCLC) (adjuvant trials) and locally advanced NSCLC (radiotherapy trials), one individual-patient data meta-analysis found a high correlation of disease-free survival (DFS) and progression-free survival (PFS) with OS at patient and trial level. In trials of adjuvant chemotherapy, correlation between disease-free survival DFS and OS were 0.83 at the individual level (95% CI 0.83-0.83) and 0.92 at trial level (95% CI 0.88-0.95). In locally advanced disease, correlation between PFS and OS was 0.77 to 0.85 at the individual level, and 0.89 to 0.97 at trial level. This study provides a 'proof' of the surrogacy of PFS and DFS on OS according to the IQWiG framework and the surrogacy of PFS and DFS on OS was classified level 2 according to Fleming hierarchy. In all the other setting, no endpoint was judged to be valid surrogate for OS.

Measuring multi-joint stiffness during single movements: numerical validation of a novel time-frequency approach.

PubMed

Piovesan, Davide; Pierobon, Alberto; DiZio, Paul; Lackner, James R

2012-01-01

This study presents and validates a Time-Frequency technique for measuring 2-dimensional multijoint arm stiffness throughout a single planar movement as well as during static posture. It is proposed as an alternative to current regressive methods which require numerous repetitions to obtain average stiffness on a small segment of the hand trajectory. The method is based on the analysis of the reassigned spectrogram of the arm's response to impulsive perturbations and can estimate arm stiffness on a trial-by-trial basis. Analytic and empirical methods are first derived and tested through modal analysis on synthetic data. The technique's accuracy and robustness are assessed by modeling the estimation of stiffness time profiles changing at different rates and affected by different noise levels. Our method obtains results comparable with two well-known regressive techniques. We also test how the technique can identify the viscoelastic component of non-linear and higher than second order systems with a non-parametrical approach. The technique proposed here is very impervious to noise and can be used easily for both postural and movement tasks. Estimations of stiffness profiles are possible with only one perturbation, making our method a useful tool for estimating limb stiffness during motor learning and adaptation tasks, and for understanding the modulation of stiffness in individuals with neurodegenerative diseases.

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

PubMed

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

2013-06-01

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

Venetoclax in Patients with Previously Treated Chronic Lymphocytic Leukemia.

PubMed

Roberts, Andrew W; Stilgenbauer, Stephan; Seymour, John F; Huang, David C S

2017-08-15

Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacologic mimic of the proteins that initiate apoptosis (a so-called BH3 mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells, which express high levels of BCL2 and rely on it to maintain their survival. As a single agent, daily venetoclax treatment induced durable responses in 79% of patients with relapsed or refractory CLL or small lymphocytic lymphoma in a phase I study, including complete remissions in 20% of patients. Its use was approved by the FDA in April 2016 for patients with previously treated del(17p) CLL on the basis of a single-arm phase II trial demonstrating a 79% response rate and an estimated 1-year progression-free survival of 72% with 400 mg/day continuous therapy. This review focuses on venetoclax, its mechanism of action, pharmacology, and clinical trial data and seeks to place it in the context of rapid advances in therapy for patients with relapsed CLL, especially those with del(17p) CLL. Clin Cancer Res; 23(16); 4527-33. ©2017 AACR . ©2017 American Association for Cancer Research.

Rapid, generalized adaptation to asynchronous audiovisual speech.

PubMed

Van der Burg, Erik; Goodbourn, Patrick T

2015-04-07

The brain is adaptive. The speed of propagation through air, and of low-level sensory processing, differs markedly between auditory and visual stimuli; yet the brain can adapt to compensate for the resulting cross-modal delays. Studies investigating temporal recalibration to audiovisual speech have used prolonged adaptation procedures, suggesting that adaptation is sluggish. Here, we show that adaptation to asynchronous audiovisual speech occurs rapidly. Participants viewed a brief clip of an actor pronouncing a single syllable. The voice was either advanced or delayed relative to the corresponding lip movements, and participants were asked to make a synchrony judgement. Although we did not use an explicit adaptation procedure, we demonstrate rapid recalibration based on a single audiovisual event. We find that the point of subjective simultaneity on each trial is highly contingent upon the modality order of the preceding trial. We find compelling evidence that rapid recalibration generalizes across different stimuli, and different actors. Finally, we demonstrate that rapid recalibration occurs even when auditory and visual events clearly belong to different actors. These results suggest that rapid temporal recalibration to audiovisual speech is primarily mediated by basic temporal factors, rather than higher-order factors such as perceived simultaneity and source identity. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Single-trial event-related potential extraction through one-unit ICA-with-reference

NASA Astrophysics Data System (ADS)

Lih Lee, Wee; Tan, Tele; Falkmer, Torbjörn; Leung, Yee Hong

2016-12-01

Objective. In recent years, ICA has been one of the more popular methods for extracting event-related potential (ERP) at the single-trial level. It is a blind source separation technique that allows the extraction of an ERP without making strong assumptions on the temporal and spatial characteristics of an ERP. However, the problem with traditional ICA is that the extraction is not direct and is time-consuming due to the need for source selection processing. In this paper, the application of an one-unit ICA-with-Reference (ICA-R), a constrained ICA method, is proposed. Approach. In cases where the time-region of the desired ERP is known a priori, this time information is utilized to generate a reference signal, which is then used for guiding the one-unit ICA-R to extract the source signal of the desired ERP directly. Main results. Our results showed that, as compared to traditional ICA, ICA-R is a more effective method for analysing ERP because it avoids manual source selection and it requires less computation thus resulting in faster ERP extraction. Significance. In addition to that, since the method is automated, it reduces the risks of any subjective bias in the ERP analysis. It is also a potential tool for extracting the ERP in online application.

Plasma and Dietary Antioxidant Status as Cardiovascular Disease Risk Factors: A Review of Human Studies

PubMed Central

Wang, Ying; Chun, Ock K.; Song, Won O.

2013-01-01

Extensive evidence has demonstrated that many antioxidants such as vitamin C, vitamin E, carotenoids and polyphenols have protective effects in preventing cardiovascular disease (CVD), a chronic disease that is mediated by oxidative stress and inflammation. This review focuses on evidence from prospective cohort studies and clinical trials in regard to the associations between plasma/dietary antioxidants and cardiovascular events. Long-term, large-scale, population-based cohort studies have found that higher levels of serum albumin, bilirubin, glutathione, vitamin E, vitamin C, and carotenoids were associated with a lower risk of CVD. Evidence from the cohort studies in regard to dietary antioxidants also supported the protective effects of dietary vitamin E, vitamin C, carotenoids, and polyphenols on CVD risk. However, results from large randomized controlled trials did not support long-term use of single antioxidant supplements for CVD prevention due to their null or even adverse effects on major cardiovascular events or cancer. Diet quality indexes that consider overall diet quality rather than single nutrients have been drawing increasing attention. Cohort studies and intervention studies that focused on diet patterns such as high total antioxidant capacity have documented protective effects on CVD risk. This review provides a perspective for future studies that investigate antioxidant intake and risk of CVD. PMID:23912327

Towards a truly mobile auditory brain-computer interface: exploring the P300 to take away.

PubMed

De Vos, Maarten; Gandras, Katharina; Debener, Stefan

2014-01-01

In a previous study we presented a low-cost, small, and wireless 14-channel EEG system suitable for field recordings (Debener et al., 2012, psychophysiology). In the present follow-up study we investigated whether a single-trial P300 response can be reliably measured with this system, while subjects freely walk outdoors. Twenty healthy participants performed a three-class auditory oddball task, which included rare target and non-target distractor stimuli presented with equal probabilities of 16%. Data were recorded in a seated (control condition) and in a walking condition, both of which were realized outdoors. A significantly larger P300 event-related potential amplitude was evident for targets compared to distractors (p<.001), but no significant interaction with recording condition emerged. P300 single-trial analysis was performed with regularized stepwise linear discriminant analysis and revealed above chance-level classification accuracies for most participants (19 out of 20 for the seated, 16 out of 20 for the walking condition), with mean classification accuracies of 71% (seated) and 64% (walking). Moreover, the resulting information transfer rates for the seated and walking conditions were comparable to a recently published laboratory auditory brain-computer interface (BCI) study. This leads us to conclude that a truly mobile auditory BCI system is feasible. © 2013.

Attentional Selection in a Cocktail Party Environment Can Be Decoded from Single-Trial EEG

PubMed Central

O'Sullivan, James A.; Power, Alan J.; Mesgarani, Nima; Rajaram, Siddharth; Foxe, John J.; Shinn-Cunningham, Barbara G.; Slaney, Malcolm; Shamma, Shihab A.; Lalor, Edmund C.

2015-01-01

How humans solve the cocktail party problem remains unknown. However, progress has been made recently thanks to the realization that cortical activity tracks the amplitude envelope of speech. This has led to the development of regression methods for studying the neurophysiology of continuous speech. One such method, known as stimulus-reconstruction, has been successfully utilized with cortical surface recordings and magnetoencephalography (MEG). However, the former is invasive and gives a relatively restricted view of processing along the auditory hierarchy, whereas the latter is expensive and rare. Thus it would be extremely useful for research in many populations if stimulus-reconstruction was effective using electroencephalography (EEG), a widely available and inexpensive technology. Here we show that single-trial (≈60 s) unaveraged EEG data can be decoded to determine attentional selection in a naturalistic multispeaker environment. Furthermore, we show a significant correlation between our EEG-based measure of attention and performance on a high-level attention task. In addition, by attempting to decode attention at individual latencies, we identify neural processing at ∼200 ms as being critical for solving the cocktail party problem. These findings open up new avenues for studying the ongoing dynamics of cognition using EEG and for developing effective and natural brain–computer interfaces. PMID:24429136

Single-trial event-related potential extraction through one-unit ICA-with-reference.

PubMed

Lee, Wee Lih; Tan, Tele; Falkmer, Torbjörn; Leung, Yee Hong

2016-12-01

In recent years, ICA has been one of the more popular methods for extracting event-related potential (ERP) at the single-trial level. It is a blind source separation technique that allows the extraction of an ERP without making strong assumptions on the temporal and spatial characteristics of an ERP. However, the problem with traditional ICA is that the extraction is not direct and is time-consuming due to the need for source selection processing. In this paper, the application of an one-unit ICA-with-Reference (ICA-R), a constrained ICA method, is proposed. In cases where the time-region of the desired ERP is known a priori, this time information is utilized to generate a reference signal, which is then used for guiding the one-unit ICA-R to extract the source signal of the desired ERP directly. Our results showed that, as compared to traditional ICA, ICA-R is a more effective method for analysing ERP because it avoids manual source selection and it requires less computation thus resulting in faster ERP extraction. In addition to that, since the method is automated, it reduces the risks of any subjective bias in the ERP analysis. It is also a potential tool for extracting the ERP in online application.

Silymarin (Livergol®) Decreases Disease Activity Score in Patients with Rheumatoid Arthritis: A Non-randomized Single-arm Clinical Trial.

PubMed

Shavandi, Mehrdad; Moini, Ali; Shakiba, Yadollah; Mashkorinia, Ahamad; Dehghani, Milad; Asar, Shirin; Kiani, Amir

2017-04-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which can lead to joint destruction and disability. Pannus formation due to chronic synovitis is the hallmark of RA. Oxidative stress as a consequence of immune cell activation and disease-modifying anti-rheumatic drugs can prevent inflammation and tissue destruction. Silymarin, an antioxidant extract from Silybum marianum, has been traditionally used for the treatment of liver diseases for decades. In the present non-randomized single-arm clinical trial (NRSACT) study we evaluated the effects of silymarin tablet (Livergol®) on inflammatory markers in stable RA patients. Disease activity score (DAS-28) was measured before and after adding silymarin to standard drug regimen used for controlling inflammation in RA patients. Silymarin significantly reduced the DAS28 related symptoms in 44 RA patients after 90 days (3.02±0.98 versus 2.3±0.74, p<0.001). The exact mechanism of therapeutic effects of silymarin in RA patients is not clear but it could be as the results of its anti-inflammatory and anti-oxidative properties. Conducting the study on larger number of patients and also measuring cytokines levels including TNF-α and IL-1β may clarify the underlying mechanisms of the anti-inflammatory effects of silymarin in RA patients.

Acute myocardial infarction and cardiogenic shock: prognostic impact of cytokines: INF-γ, TNF-α, MIP-1β, G-CSF, and MCP-1β.

PubMed

Prondzinsky, R; Unverzagt, S; Lemm, H; Wegener, N; Heinroth, K; Buerke, U; Fiedler, M; Thiery, J; Haerting, J; Werdan, K; Buerke, M

2012-09-01

The IABP SHOCK trial was designed as a morbidity-based randomized controlled trial to determine the effect of intraaortic balloon pulsation (IABP) in patients with infarct-related cardiogenic shock (CS). The primary endpoint was the change in the APACHE II score over a 4-day period. The prospective hypothesis was that adding IABP therapy to "standard care" would reduce CS-triggered multiorgan dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with additional IABP support. In an inflammatory marker substudy, we analyzed the prognostic value of the cytokines interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1β (MIP-1β), granulocyte-colony stimulating factor (G-CSF), and monocyte chemoattractant protein-1β (MCP-1β). We also investigated the influence of IABP support, age, and gender on cytokine levels. The inflammatory marker substudy of the prospective, randomized, controlled, open label IABP SHOCK Trial (ClinicalTrials.gov ID NCT00469248). A prospective, randomized, single-center study in a 12-bed intensive care unit at a university hospital was performed. A total of 40 consecutive patients were enrolled. The observational period was 96 h. The investigated cytokines showed a significant contribution in the prediction of mortality. Initial (on admission) and maximal cytokine levels during the observational period showed a similar predictive power. Patients with elevated levels of pro- and antiinflammatory cytokines had a higher risk of dying. The maximal level measured over the observation period in the hospital was also suited to identify the survivors. Close correlations between maximal cytokine levels resulted in the choice of only one independent marker (MIP-1β) into the multivariate model (OR 1.024, 95% CI 1.005-1.043). Initial cytokine levels were also suitable to predict the survivors; the risk of death significantly increases with increasing IFN-γ level (OR 1.119, 95% CI 1.005-1.246). Cytokine levels were not affected by the presence of IABP support. Age (< 75 or > 75 years) and gender did not have a clinically relevant effect on INF-γ, TNF-α, MIP-1β, G-CSF, and MCP-1 in CS patients. The inflammatory response in patients with myocardial infarction complicated by CS, as reflected by the inflammatory markers INF-γ, TNF-α, MIP-1β, G-CSF, and MCP-1β, have been shown to be of prognostic value in estimating clinical outcome.

Effectiveness of a self-management program for dual sensory impaired seniors in aged care settings: study protocol for a cluster randomized controlled trial

PubMed Central

2013-01-01

Background Five to 25 percent of residents in aged care settings have a combined hearing and visual sensory impairment. Usual care is generally restricted to single sensory impairment, neglecting the consequences of dual sensory impairment on social participation and autonomy. The aim of this study is to evaluate the effectiveness of a self-management program for seniors who acquired dual sensory impairment at old age. Methods/Design In a cluster randomized, single-blind controlled trial, with aged care settings as the unit of randomization, the effectiveness of a self-management program will be compared to usual care. A minimum of 14 and maximum of 20 settings will be randomized to either the intervention cluster or the control cluster, aiming to include a total of 132 seniors with dual sensory impairment. Each senior will be linked to a licensed practical nurse working at the setting. During a five to six month intervention period, nurses at the intervention clusters will be trained in a self-management program to support and empower seniors to use self-management strategies. In two separate diaries, nurses keep track of the interviews with the seniors and their reflections on their own learning process. Nurses of the control clusters offer care as usual. At senior level, the primary outcome is the social participation of the seniors measured using the Hearing Handicap Questionnaire and the Activity Card Sort, and secondary outcomes are mood, autonomy and quality of life. At nurse level, the outcome is job satisfaction. Effectiveness will be evaluated using linear mixed model analysis. Discussion The results of this study will provide evidence for the effectiveness of the Self-Management Program for seniors with dual sensory impairment living in aged care settings. The findings are expected to contribute to the knowledge on the program’s potential to enhance social participation and autonomy of the seniors, as well as increasing the job satisfaction of the licensed practical nurses. Furthermore, an extensive process evaluation will take place which will offer insight in the quality and feasibility of the sampling and intervention process. If it is shown to be effective and feasible, this Self-Management Program could be widely disseminated. Clinical trials registration ClinicalTrials.gov, NCT01217502. PMID:24099315

Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing's sarcoma.

PubMed

Dutton, P; Love, S B; Billingham, L; Hassan, A B

2018-05-01

Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency.

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.

A Practical Bayesian Design to Identify the Maximum Tolerated Dose Contour for Drug Combination Trials

PubMed Central

Zhang, Liangcai; Yuan, Ying

2016-01-01

Drug combination therapy has become the mainstream approach to cancer treatment. One fundamental feature that makes combination trials different from single-agent trials is the existence of the maximum tolerated dose (MTD) contour, i.e., multiple MTDs. As a result, unlike single-agent phase I trials, which aim to find a single MTD, it is often of interest to find the MTD contour for combination trials. We propose a new dose-finding design, the waterfall design, to find the MTD contour for drug combination trials. Taking the divide-and-conquer strategy, the waterfall design divides the task of finding the MTD contour into a sequence of one-dimensional dose-finding processes, known as subtrials. The subtrials are conducted sequentially in a certain order, such that the results of each subtrial will be used to inform the design of subsequent subtrials. Such information borrowing allows the waterfall design to explore the two-dimensional dose space efficiently using a limited sample size, and decreases the chance of overdosing and underdosing patients. To accommodate the consideration that doses on the MTD contour may have very different efficacy or synergistic effects due to drug-drug interaction, we further extend our approach to a phase I/II design with the goal of finding the MTD with the highest efficacy. Simulation studies show that the waterfall design is safer and has higher probability of identifying the true MTD contour than some existing designs. The R package “BOIN” to implement the waterfall design is freely available from CRAN. PMID:27580928

Reliability of the measures of weight-bearing distribution obtained during quiet stance by digital scales in subjects with and without hemiparesis.

PubMed

de Araujo-Barbosa, Paulo Henrique Ferreira; de Menezes, Lidiane Teles; Costa, Abraão Souza; Couto Paz, Clarissa Cardoso Dos Santos; Fachin-Martins, Emerson

2015-05-01

Described as an alternative way of assessing weight-bearing asymmetries, the measures obtained from digital scales have been used as an index to classify weight-bearing distribution. This study aimed to describe the intra-test and the test/retest reliability of measures in subjects with and without hemiparesis during quiet stance. The percentage of body weight borne by one limb was calculated for a sample of subjects with hemiparesis and for a control group that was matched by gender and age. A two-way analysis of variance was used to verify the intra-test reliability. This analysis was calculated using the differences between the averages of the measures obtained during single, double or triple trials. The intra-class correlation coefficient (ICC) was utilized and data plotted using the Bland-Altman method. The intra-test analysis showed significant differences, only observed in the hemiparesis group, between the measures obtained by single and triple trials. Excellent and moderate ICC values (0.69-0.84) between test and retest were observed in the hemiparesis group, while for control groups ICC values (0.41-0.74) were classified as moderate, progressing from almost poor for measures obtained by a single trial to almost excellent for those obtained by triple trials. In conclusion, good reliability ranging from moderate to excellent classifications was found for participants with and without hemiparesis. Moreover, an improvement of the repeatability was observed with fewer trials for participants with hemiparesis, and with more trials for participants without hemiparesis.

Role of vitamin D3 in treatment of lumbar disc herniation--pain and sensory aspects: study protocol for a randomized controlled trial.

PubMed

Sedighi, Mahsa; Haghnegahdar, Ali

2014-09-25

Vitamin D receptors have been identified in the spinal cord, nerve roots, dorsal root ganglia and glial cells, and its genetic polymorphism association with the development of lumbar disc degeneration and herniation has been documented. Metabolic effects of active vitamin D metabolites in the nucleus pulposus and annulus fibrosus cells have been studied. Lumbar disc herniation is a process that involves immune and inflammatory cells and processes that are targets for immune regulatory actions of vitamin D as a neurosteroid hormone. In addition to vitamin D's immune modulatory properties, its receptors have been identified in skeletal muscles. It also affects sensory neurons to modulate pain. In this study, we aim to study the role of vitamin D3 in discogenic pain and related sensory deficits. Additionally, we will address how post-treatment 25-hydroxy vitamin D3 level influences pain and sensory deficits severity. The cut-off value for serum 25-hydroxy vitamin D3 that would be efficacious in improving pain and sensory deficits in lumbar disc herniation will also be studied. We will conduct a randomized, placebo-controlled, double-blind clinical trial. Our study population will include 380 cases with one-level and unilateral lumbar disc herniation with duration of discogenic pain less than 8 weeks. Individuals who do not have any contraindications, will be divided into three groups based on serum 25-hydroxy vitamin D3 level, and each group will be randomized to receive either a single-dose 300,000-IU intramuscular injection of vitamin D3 or placebo. All patients will be under conservative treatment. Pre-treatment and post-treatment assessments will be performed with the McGill Pain Questionnaire and a visual analogue scale. For the 15-day duration of this study, questionnaires will be filled out during telephone interviews every 3 days (a total of five times). The initial and final interviews will be scheduled at our clinic. After 15 days, serum 25-hydroxy vitamin D3 levels will be measured for those who have received vitamin D3 (190 individuals). Iranian Registry for Clinical Trials ID: IRCT2014050317534N1 (trial registration: 5 June 2014).

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

Modelling Trial-by-Trial Changes in the Mismatch Negativity

PubMed Central

Lieder, Falk; Daunizeau, Jean; Garrido, Marta I.; Friston, Karl J.; Stephan, Klaas E.

2013-01-01

The mismatch negativity (MMN) is a differential brain response to violations of learned regularities. It has been used to demonstrate that the brain learns the statistical structure of its environment and predicts future sensory inputs. However, the algorithmic nature of these computations and the underlying neurobiological implementation remain controversial. This article introduces a mathematical framework with which competing ideas about the computational quantities indexed by MMN responses can be formalized and tested against single-trial EEG data. This framework was applied to five major theories of the MMN, comparing their ability to explain trial-by-trial changes in MMN amplitude. Three of these theories (predictive coding, model adjustment, and novelty detection) were formalized by linking the MMN to different manifestations of the same computational mechanism: approximate Bayesian inference according to the free-energy principle. We thereby propose a unifying view on three distinct theories of the MMN. The relative plausibility of each theory was assessed against empirical single-trial MMN amplitudes acquired from eight healthy volunteers in a roving oddball experiment. Models based on the free-energy principle provided more plausible explanations of trial-by-trial changes in MMN amplitude than models representing the two more traditional theories (change detection and adaptation). Our results suggest that the MMN reflects approximate Bayesian learning of sensory regularities, and that the MMN-generating process adjusts a probabilistic model of the environment according to prediction errors. PMID:23436989

Statin therapy for acute respiratory distress syndrome: an individual patient data meta-analysis of randomised clinical trials.

PubMed

Nagendran, Myura; McAuley, Daniel F; Kruger, Peter S; Papazian, Laurent; Truwit, Jonathon D; Laffey, John G; Thompson, B Taylor; Clarke, Mike; Gordon, Anthony C

2017-05-01

We performed an individual patient data meta-analysis to assess the possible benefits and harms of statin therapy in adults with acute respiratory distress syndrome (ARDS) and to investigate effects in specific ARDS subgroups. We identified randomised clinical trials up to 31 October 2016 that had investigated statin therapy versus placebo in patients with ARDS. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed for primary and secondary outcomes, and one-stage regression models with single treatment-covariate interactions for subgroup analyses. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Six trials with a total of 1755 patients were included. For the primary outcomes, there was no significant effect of statin therapy on 28-day mortality [relative risk (RR) 1.03, 95% CI 0.86-1.23], ventilator-free days (mean difference 0.34 days, 95% CI -0.68 to 1.36) or serious adverse events (RR 1.14, 95% CI 0.84-1.53). There was a significantly increased incidence of raised serum creatine kinase or transaminase levels with statin therapy (106/879; 12.1%) versus control (78/876; 8.9%) (RR 1.40, 95% CI 1.07-1.83, p = 0.015). There were no significant treatment-covariate interactions in the predefined subgroups investigated. We found no clinical benefit from initiation of statin therapy in adult patients with ARDS, either overall or in predefined subgroups. While there was an increased incidence of raised serum creatine kinase and transaminase levels, there was no difference in serious adverse events among groups. Therefore, we do not recommend initiation of statin therapy for the treatment of ARDS.

Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial.

PubMed

Nowak, Albina; Boesch, Lukas; Andres, Erik; Battegay, Edouard; Hornemann, Thorsten; Schmid, Christoph; Bischoff-Ferrari, Heike A; Suter, Paolo M; Krayenbuehl, Pierre-Alexandre

2016-12-01

Vitamin D deficiency is frequent and has been associated with fatigue in uncontrolled trials. This is the first double-blind placebo-controlled clinical trial to investigate the efficacy of per os vitamin D3 (cholecalciferol) in treating fatigue among otherwise healthy persons with low serum 25-hydroxyvitamin D (25(OH)D) levels. We enrolled 120 individuals (mean age 29 ± 6 years, 53% women) presenting with fatigue and vitamin D deficiency (serum 25(OH)D < 20 μg/L). Participants were randomized to a single oral dose of 100,000 units of vitamin D or placebo. The primary endpoint was intra-individual change in the fatigue assessment scale (FAS) at 4 weeks after treatment. The mean age of the participants was 29 ± 6 years, 53% were women. Mean FAS decreased significantly more in the vitamin D group (-3.3 ± 5.3; 95% confidence interval [CI] for change -14.1 to 4.1) compared with placebo (-0.8 ± 5.3; 95% CI for change -9.0 to 8.7); (P = 0.01). Amelioration of fatigue was reported more frequently in vitamin D than in placebo group (42 [72%] vs. 31 [50%]; P = 0.01; odds ratio [OR] 2.63, 95% CI for OR 1.23-5.62). Among all participants, improvement in fatigue score correlated with the rise in 25(OH)D level (R = -0.22, P = 0.02). Vitamin D treatment significantly improved fatigue in otherwise healthy persons with vitamin D deficiency.This study was registered at the www.ClinicalTrials.gov Protocol ID NCT02022475.

Impact of copula directional specification on multi-trial evaluation of surrogate endpoints

PubMed Central

Renfro, Lindsay A.; Shang, Hongwei; Sargent, Daniel J.

2014-01-01

Evaluation of surrogate endpoints using patient-level data from multiple trials is the gold standard, where multi-trial copula models are used to quantify both patient-level and trial-level surrogacy. While limited consideration has been given in the literature to copula choice (e.g., Clayton), no prior consideration has been given to direction of implementation (via survival versus distribution functions). We demonstrate that evenwith the “correct” copula family, directional misspecification leads to biased estimates of patient-level and trial-level surrogacy. We illustrate with a simulation study and a re-analysis of disease-free survival as a surrogate for overall survival in early stage colon cancer. PMID:24905465

Accounting for correlation in network meta-analysis with multi-arm trials.

PubMed

Franchini, A J; Dias, S; Ades, A E; Jansen, J P; Welton, N J

2012-06-01

Multi-arm trials (trials with more than two arms) are particularly valuable forms of evidence for network meta-analysis (NMA). Trial results are available either as arm-level summaries, where effect measures are reported for each arm, or as contrast-level summaries, where the differences in effect between arms compare with the control arm chosen for the trial. We show that likelihood-based inference in both contrast-level and arm-level formats is identical if there are only two-arm trials, but that if there are multi-arm trials, results from the contrast-level format will be incorrect unless correlations are accounted for in the likelihood. We review Bayesian and frequentist software for NMA with multi-arm trials that can account for this correlation and give an illustrative example of the difference in estimates that can be introduced if the correlations are not incorporated. We discuss methods of imputing correlations when they cannot be derived from the reported results and urge trialists to report the standard error for the control arm even if only contrast-level summaries are reported. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.

Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission

PubMed Central

Graves, Patricia M; Gelband, Hellen; Garner, Paul

2015-01-01

Background Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ) and other 8-aminoquinolines (8AQ); these drugs could prevent parasite transmission from infected people to mosquitoes, and consequently reduce the incidence of malaria. However, PQ will not directly benefit the individual, and could be harmful to those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In 2010, The World Health Organization (WHO) recommended a single dose of PQ at 0.75 mg/kg, alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013 the WHO revised this to 0.25 mg/kg due to concerns about safety. Objectives To assess whether giving PQ or an alternative 8AQ alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events when PQ is given for this purpose. Search methods We searched the following databases up to 10 Feb 2014 for trials: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs comparing PQ (or alternative 8AQ) given as a single dose or short course alongside treatment for P. falciparum malaria with malaria treatment given without PQ/8AQ in adults or children. Data collection and analysis Two authors independently screened all abstracts, applied inclusion criteria, and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, as well as secondary outcomes of asexual clearance time and recrudescence. We stratified by whether the malaria treatment regimen included an artemisinin derivative or not; by PQ dose category (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg); and by PQ schedules. We used the GRADE approach to assess evidence quality. Main results We included 17 RCTs and one quasi-RCT. Eight studies tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining ten trials either did not report on whether they tested (8), or reported that they did not test (2). Nine trials included study arms with artemisinin-based malaria treatment regimens, and eleven included study arms with non-artemisinin-based treatments. Only two trials evaluated PQ given at low doses (0.25 mg/kg in one and 0.1 mg/kg in the other). PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence, or entomological inoculation rate), and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two thirds with high dose PQ category (RR 0.29, 95% CI 0.22 to 0.37, seven trials, 1380 participants, high quality evidence), and with medium dose PQ category (RR 0.34, 95% CI 0.19 to 0.59, two trials, 269 participants, high quality evidence), but the trial evaluating low dose PQ category (0.1 mg/kg) did not demonstrate an effect (RR 0.67, 95% CI 0.44 to 1.02, one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline, and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory evaluated infectiousness to mosquitoes, and report that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by around half with high dose PQ category (RR 0.44, 95% CI 0.27 to 0.70, three trials, 206 participants, high quality evidence), and by around a third with medium dose category (RR 0.62, 0.50 to 0.76, two trials, 283 participants, high quality evidence), but the single trial using low dose PQ category did not demonstrate a difference between groups (one trial, 59 participants, very low quality evidence). Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis. Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (n = 112) preclude a definite conclusion. Authors' conclusions In individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic settings approaching elimination, or in highly-endemic settings where many people are infected but have no symptoms and are unlikely to be treated. For the currently recommended low dose regimen, there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved. Most trials excluded people with G6PD deficiency, and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course. PLAIN LANGUAGE SUMMARY A single dose of primaquine added to malaria treatment to prevent malaria transmission We conducted a review of the effects of adding a single dose (or short course) of primaquine to malaria treatment with the aim of reducing the transmission of malaria. We included 17 randomized controlled trials and one quasi-randomized controlled trial. What is primaquine and how might it reduce transmission Primaquine is an antimalarial drug which does not cure malaria illness, but is known to kill the gametocyte stage of the malaria parasite which infects mosquitoes when they bite humans. Primaquine is also known to have potentially serious side effects in people with an enzyme deficiency common in many malaria endemic settings (glucose-6-phosphate dehydrogenase (G6PD) deficiency). In these people, high doses of primaquine given over several days sometimes destroys red blood cells, causing anaemia and, in some cases, possibly life-threatening effects. The World Health Organization (WHO) recommends adding a single dose of primaquine to malaria treatment with the intention of reducing malaria transmission and to contribute to malaria elimination. This recommendation was made in 2010, but in 2013 the WHO amended its recommendation from a dose of 0.75 mg/kg to 0.25 mg/kg due to concerns about safety, and indirect evidence suggesting this was as effective as the higher dose.This review examines the evidence of benefits and harms of using primaquine in this way, and looks for evidence that primaquine will reduce malaria transmission in communities. What the research says We did not find any studies that tested whether primaquine added to malaria treatment reduces the community transmission of malaria. When added to current treatments for malaria (artemisinin-based combination therapy), we found no studies evaluating the effects of primaquine on the number of mosquitoes infected. However, primaquine does reduce the duration of infectiousness (the period that gametocytes are detected circulating in the blood) when given at doses of 0.4 mg/kg or above (high quality evidence). We only found one study using 0.1 mg/kg but this study did not conclusively show that primaquine was still effective at this dose (low quality evidence). When added to older treatments for malaria, two studies showed that primaquine at doses of 0.75 mg/kg reduced the number of mosquitoes infected after biting humans (low quality evidence). Doses above 0.4 mg/kg reduced the duration of detectable gametocytes (high quality evidence), but in a single study of the currently recommended 0.25 mg/kg no effect was demonstrated (very low quality evidence). Some studies excluded patients with G6PD deficiency, some included them, and some did not comment. Overall the safety of PQ given as a single dose was poorly evaluated across all studies, so these data do not demonstrate whether the drug is safe or potentially harmful at this dosing level. PMID:25693791

Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission

PubMed Central

Graves, Patricia M; Gelband, Hellen; Garner, Paul

2014-01-01

Background Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ) and other 8-aminoquinolines (8AQ); these drugs could prevent parasite transmission from infected people to mosquitoes, and consequently reduce the incidence of malaria. However, PQ will not directly benefit the individual, and could be harmful to those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In 2010, The World Health Organization (WHO) recommended a single dose of PQ at 0.75 mg/kg, alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013 the WHO revised this to 0.25 mg/kg due to concerns about safety. Objectives To assess whether giving PQ or an alternative 8AQ alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events when PQ is given for this purpose. Search methods We searched the following databases up to 10 Feb 2014 for trials: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs comparing PQ (or alternative 8AQ) given as a single dose or short course alongside treatment for P. falciparum malaria with malaria treatment given without PQ/8AQ in adults or children. Data collection and analysis Two authors independently screened all abstracts, applied inclusion criteria, and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, as well as secondary outcomes of asexual clearance time and recrudescence. We stratified by whether the malaria treatment regimen included an artemisinin derivative or not; by PQ dose category (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg); and by PQ schedules. We used the GRADE approach to assess evidence quality. Main results We included 17 RCTs and one quasi-RCT. Eight studies tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining ten trials either did not report on whether they tested (8), or reported that they did not test (2). Nine trials included study arms with artemisinin-based malaria treatment regimens, and eleven included study arms with non-artemisinin-based treatments. Only two trials evaluated PQ given at low doses (0.25 mg/kg in one and 0.1 mg/kg in the other). PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence, or entomological inoculation rate), and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two thirds with high dose PQ category (RR 0.29, 95% CI 0.22 to 0.37, seven trials, 1380 participants, high quality evidence), and with medium dose PQ category (RR 0.34, 95% CI 0.19 to 0.59, two trials, 269 participants, high quality evidence), but the trial evaluating low dose PQ category (0.1 mg/kg) did not demonstrate an effect (RR 0.67, 95% CI 0.44 to 1.02, one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline, and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory evaluated infectiousness to mosquitoes, and report that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by around half with high dose PQ category (RR 0.44, 95% CI 0.27 to 0.70, three trials, 206 participants, high quality evidence), and by around a third with medium dose category (RR 0.62, 0.50 to 0.76, two trials, 283 participants, high quality evidence), but the single trial using low dose PQ category did not demonstrate a difference between groups (one trial, 59 participants, very low quality evidence). Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis. Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (n = 112) preclude a definite conclusion. Authors' conclusions In individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic settings approaching elimination, or in highly-endemic settings where many people are infected but have no symptoms and are unlikely to be treated. For the currently recommended low dose regimen, there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved. Most trials excluded people with G6PD deficiency, and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course. PLAIN LANGUAGE SUMMARY A single dose of primaquine added to malaria treatment to prevent malaria transmission We conducted a review of the effects of adding a single dose (or short course) of primaquine to malaria treatment with the aim of reducing the transmission of malaria. We included 17 randomized controlled trials and one quasi-randomized controlled trial. What is primaquine and how might it reduce transmission Primaquine is an antimalarial drug which does not cure malaria illness, but is known to kill the gametocyte stage of the malaria parasite which infects mosquitoes when they bite humans. Primaquine is also known to have potentially serious side effects in people with an enzyme deficiency common in many malaria endemic settings (glucose-6-phosphate dehydrogenase (G6PD) deficiency). In these people, high doses of primaquine given over several days sometimes destroys red blood cells, causing anaemia and, in some cases, possibly life-threatening effects. The World Health Organization (WHO) recommends adding a single dose of primaquine to malaria treatment with the intention of reducing malaria transmission and to contribute to malaria elimination. This recommendation was made in 2010, but in 2013 the WHO amended its recommendation from a dose of 0.75 mg/kg to 0.25 mg/kg due to concerns about safety, and indirect evidence suggesting this was as effective as the higher dose.This review examines the evidence of benefits and harms of using primaquine in this way, and looks for evidence that primaquine will reduce malaria transmission in communities. What the research says We did not find any studies that tested whether primaquine added to malaria treatment reduces the community transmission of malaria. When added to current treatments for malaria (artemisinin-based combination therapy), we found no studies evaluating the effects of primaquine on the number of mosquitoes infected. However, primaquine does reduce the duration of infectiousness (the period that gametocytes are detected circulating in the blood) when given at doses of 0.4 mg/kg or above (high quality evidence). We only found one study using 0.1 mg/kg but this study did not conclusively show that primaquine was still effective at this dose (low quality evidence). When added to older treatments for malaria, two studies showed that primaquine at doses of 0.75 mg/kg reduced the number of mosquitoes infected after biting humans (low quality evidence). Doses above 0.4 mg/kg reduced the duration of detectable gametocytes (high quality evidence), but in a single study of the currently recommended 0.25 mg/kg no effect was demonstrated (very low quality evidence). Some studies excluded patients with G6PD deficiency, some included them, and some did not comment. Overall the safety of PQ given as a single dose was poorly evaluated across all studies, so these data do not demonstrate whether the drug is safe or potentially harmful at this dosing level. PMID:24979199

Single-Trial Analysis of V1 Responses Suggests Two Transmission States

NASA Technical Reports Server (NTRS)

Shah, A. S.; Knuth, K. H.; Truccolo, W. A.; Mehta, A. D.; McGinnis, T.; OConnell, N.; Ding, M.; Bressler, S. L.; Schroeder, C. E.

2002-01-01

Sensory processing in the visual, auditory, and somatosensory systems is often studied by recording electrical activity in response to a stimulus of interest. Typically, multiple trial responses to the stimulus are averaged to isolate the stereotypic response from noise. However, averaging ignores dynamic variability in the neuronal response, which is potentially critical to understanding stimulus-processing schemes. Thus, we developed the multiple component, Event-Related Potential (mcERP) model. This model asserts that multiple components, defined as stereotypic waveforms, comprise the stimulus-evoked response and that these components may vary in amplitude and latency from trial to trial. Application of this model to data recorded simultaneously from all six laminae of V1 in an awake, behaving monkey performing a visual discrimination yielded three components. The first component localized to granular V1, the second was located in supragranular V1, and the final component displayed a multi-laminar distribution. These modeling results, which take into account single-trial response dynamics, illustrated that the initial activation of VI occurs in the granular layer followed by activation in the supragranular layers. This finding is expected because the average response in those layers demonstrates the same progression and because anatomical evidence suggests that the feedforward input in V1 enters the granular layer and progresses to supragranular layers. In addition to these findings, the granular component of the model displayed several interesting trial-to-trial characteristics including (1) a bimodal latency distribution, (2) a latency-related variation in response amplitude, (3) a latency correlation with the supragranular component, and (4) an amplitude and latency association with the multi-laminar component. Direct analyses of the single-trial data were consistent with these model predictions. These findings suggest that V1 has at least 2 transmission states, which may be modulated by various effects such as attention, dynamics in local EEG rhythm, or variation in sensory inputs.

Histone deacetylase inhibitors: current status and overview of recent clinical trials.

PubMed

Ma, Xujun; Ezzeldin, Hany H; Diasio, Robert B

2009-10-01

Histone deacetylase (HDAC) inhibitors are a new group of anticancer agents that have a potential role in the regulation of gene expression, induction of cell death, apoptosis and cell cycle arrest of cancer cells by altering the acetylation status of chromatin and other non-histone proteins. In clinical trials, HDAC inhibitors have demonstrated promising antitumour activity as monotherapy in cutaneous T-cell lymphoma and other haematological malignancies. In solid tumours, several HDAC inhibitors have been shown to be efficacious as single agents; however, results of most clinical trials were in favour of using HDAC inhibitors either prior to the initiation of chemotherapy or in combination with other treatments. Currently, the molecular basis of response to HDAC inhibitors in patients is not fully understood. In this review, we summarize the current status of HDAC inhibitors, as single agents or in combination with other agents in different phases of clinical trials. In most of the clinical trials, HDAC inhibitors were tolerable and exerted biological or antitumor activity. HDAC inhibitors have been studied in phase I, II and III clinical trials with variable efficacy. The combination of HDAC inhibitors with other anticancer agents including epigenetic or chemotherapeutic agents demonstrated favourable clinical outcome.

Field trial of solvent-free emulsion in Oregon : final report.

DOT National Transportation Integrated Search

2003-03-01

This final report summarizes construction, laboratory and performance information gathered by ODOT personnel from a single field trial of solvent-free emulsion mix constructed in June 2001. The solvent-free emulsion mix presented several placement pr...

Randomized, Placebo-Controlled, Single-Ascending-Dose Study of BMS-791325, a Hepatitis C Virus (HCV) NS5B Polymerase Inhibitor, in HCV Genotype 1 Infection

PubMed Central

Lemm, Julie; Eley, Timothy; Liu, Menping; Berglind, Anna; Sherman, Diane; Lawitz, Eric; Vutikullird, Apinya B.; Tebas, Pablo; Gao, Min; Pasquinelli, Claudio; Grasela, Dennis M.

2014-01-01

BMS-791325 is a nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B polymerase with low-nanomolar potency against genotypes 1a (50% effective concentration [EC50], 3 nM) and 1b (EC50, 7 nM) in vitro. BMS-791325 safety, pharmacokinetics, and antiviral activity were evaluated in a double-blind, placebo-controlled, single-ascending-dose study in 24 patients (interferon naive and experienced) with chronic HCV genotype 1 infection, randomized (5:1) to receive a single dose of BMS-791325 (100, 300, 600, or 900 mg) or placebo. The prevalence and phenotype of HCV variants at baseline and specific posttreatment time points were assessed. Antiviral activity was observed in all cohorts, with a mean HCV RNA decline of ≈2.5 log10 copies/ml observed 24 h after a single 300-mg dose. Mean plasma half-life among cohorts was 7 to 9 h; individual 24-hour levels exceeded the protein-adjusted EC90 for genotype 1 at all doses. BMS-791325 was generally well tolerated, with no serious adverse events or discontinuations. Enrichment for resistance variants was not observed at 100 to 600 mg. At 900 mg, variants (P495L/S) associated with BMS-791325 resistance in vitro were transiently observed in one patient, concurrent with an observed HCV RNA decline of 3.4 log10 IU/ml, but were replaced with wild type by 48 h. Single doses of BMS-791325 were well tolerated; demonstrated rapid, substantial, and exposure-related antiviral activity; displayed dose-related increases in exposure; and showed viral kinetic and pharmacokinetic profiles supportive of once- or twice-daily dosing. These results support its further development in combination with other direct-acting antivirals for HCV genotype 1 infection. (This trial has been registered at ClinicalTrials.gov under registration no. NCT00664625.) PMID:24733462

(99m)Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials.

PubMed

Belhocine, Tarik Z; Blankenberg, Francis G; Kartachova, Marina S; Stitt, Larry W; Vanderheyden, Jean-Luc; Hoebers, Frank J P; Van de Wiele, Christophe

2015-12-01

(99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative (99m)Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases. Included in this review were 17 clinical trials investigating quantitative (99m)Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95% CI) were calculated using Meta-Disc software version 1.4. Absolute quantification and/or relative quantification of (99m)Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of (99m)Tc-annexin A5 tumor uptake and delta (Δ) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), ΔTBR, tumor-to-noise ratio, relative tumor ratio (TR), ΔTR, standardized tumor uptake ratio (STU), ΔSTU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute ΔU and percentage (ΔU%), maximum ΔU counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm(3). Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials, an increase of ≥25% in uptake following treatment was considered a significant threshold for an apoptotic tumor response (partial response, complete response). In three other phase I/II clinical trials, increases of ≥28%, ≥42% and ≥47% in uptake following treatment were found to be the mean cut-off levels in responders. In a phase II/III multicenter clinical trial, an increase of ≥23% in uptake following treatment was found to be the minimum cut-off level for a tumor response. In one clinical trial, no significant difference in (99m)Tc-annexin A5 uptake in terms of %ID was found in healthy tissues after chemotherapy compared to baseline. In two other clinical trials, intraobserver and interobserver measurements of (99m)Tc-annexin A5 tumor uptake were found to be reproducible (mean difference <5%, kappa =  0.90 and 0.82, respectively) and to be highly correlated with treatment outcome (Spearman r = 0.99, p < 0.0001). The meta-analysis demonstrated a pooled positive PPV of 100% (95% CI 92 - 100%) and a pooled NPV of 70% (95% CI 55 - 82%) for prediction of a tumor response after the first course of chemotherapy and/or radiotherapy in terms of ΔU%. In a symmetric sROC analysis, the AUC was 0.919 and the Q* index was 85.21 %. Quantitative (99m)Tc-annexin A5 imaging has been investigated in clinical trials for the assessment of apoptotic tumor responses. This meta-analysis showed a high pooled PPV and a moderate pooled NPV with ΔU cut-off values ranging between 20% and 30%. Standardization of quantification and harmonization of results are required for high-quality clinical research. A standardized uptake value score (SUV, ΔSUV) using quantitative SPECT/CT imaging may be a promising approach to the simple, reproducible and semiquantitative assessment of apoptotic tumor changes.

Mucosal Vaccination for Prevention of HIV Infection and AIDS.

PubMed

Aldovini, Anna

2016-01-01

Most of HIV infections occur via the genital tract or the rectum and HIV replicates at high levels in lymphoid organs and intestinal mucosa, likely requiring a more diversified immunity than pathogens restricted to a single mucosal site, such as the gastrointestinal tract for Vibrio cholera, or the respiratory airways for the influenza virus. Numerous AIDS vaccine candidates are under development and a general observation obtained from preclinical trials in non-human primates that failed to provide sterilizing immunity is that some infection protection or delayed onset of disease is observed in the presence of anti-SIV immunity. Recent clinical trials support difficulties to reproduce in humans the results observed in simian models, but at least one of them indicated that some protection of infection can be achieved. However, given the limited efficacy observed in the RV144 trial and concerns voiced in its statistical interpretation, preclinical trials should explore more effective immunogens, whether new or as combinations of existing ones, and mucosal routes of vaccinations in addition to the systemic routes, with the goal to maximize vaccination-mediated protection. The rationale for generating both strong mucosal and systemic immunity comes from animal experiments, recent clinical trials, and other successful vaccines currently in use. Mucosal responses against SIV have been induced with a variety of SIV antigens and via different mucosal routes with a spectrum of effects on protection. This review covers the rational and the experimental data that support the validity to explore mucosal immunization for HIV infection and AIDS prevention.

Out-of-hospital tracheal intubation with single-use versus reusable metal laryngoscope blades: a multicenter randomized controlled trial.

PubMed

Jabre, Patricia; Galinski, Michel; Ricard-Hibon, Agnes; Devaud, Marie Laure; Ruscev, Mirko; Kulstad, Erik; Vicaut, Eric; Adnet, Fréderic; Margenet, Alain; Marty, Jean; Combes, Xavier

2011-03-01

Emergency tracheal intubation is reported to be more difficult with single-use plastic than with reusable metal laryngoscope blades in both inhospital and out-of-hospital settings. Single-use metal blades have been developed but have not been compared with conventional metal blades. This controlled trial compares the efficacy and safety of single-use metal blades with reusable metal blades in out-of-hospital emergency tracheal intubation. This randomized controlled trial was carried out in France with out-of-hospital emergency medical units (Services de Médecine d'Urgence et de Réanimation). This was a multicenter prospective noninferiority randomized controlled trial in adult out-of-hospital patients requiring emergency tracheal intubation. Patients were randomly assigned to either single-use or reusable metal laryngoscope blades and intubated by a senior physician or a nurse anesthetist. The primary outcome was first-pass intubation success. Secondary outcomes were incidence of difficult intubation, need for alternate airway devices, and early intubation-related complications (esophageal intubation, mainstem intubation, vomiting, pulmonary aspiration, dental trauma, bronchospasm or laryngospasm, ventricular tachycardia, arterial desaturation, hypotension, or cardiac arrest). The study included 817 patients, including 409 intubated with single-use blades and 408 with a reusable blade. First-pass intubation success was similar in both groups: 292 (71.4%) for single-use blades, 290 (71.1%) for reusable blades. The 95% confidence interval (CI) for the difference in treatments (0.3%; 95% CI -5.9% to 6.5%) did not include the prespecified inferiority margin of -7%. There was no difference in rate of difficult intubation (difference 3%; 95% CI -7% to 2%), need for alternate airway (difference 4%; 95% CI -8% to 1%), or early complication rate (difference 3%; 95% CI -3% to 8%). First-pass out-of-hospital tracheal intubation success with single-use metal laryngoscopy blades was noninferior to first-pass success with reusable metal laryngoscope blades. Copyright © 2010 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Appetite, appetite hormone and energy intake responses to two consecutive days of aerobic exercise in healthy young men.

PubMed

Douglas, Jessica A; King, James A; McFarlane, Ewan; Baker, Luke; Bradley, Chloe; Crouch, Nicole; Hill, David; Stensel, David J

2015-09-01

Single bouts of exercise do not cause compensatory changes in appetite, food intake or appetite regulatory hormones on the day that exercise is performed. It remains possible that such changes occur over an extended period or in response to a higher level of energy expenditure. This study sought to test this possibility by examining appetite, food intake and appetite regulatory hormones (acylated ghrelin, total peptide-YY, leptin and insulin) over two days, with acute bouts of exercise performed on each morning. Within a controlled laboratory setting, 15 healthy males completed two, 2-day long (09:00-16:00) experimental trials (exercise and control) in a randomised order. On the exercise trial participants performed 60 min of continuous moderate-high intensity treadmill running (day one: 70.1 ± 2.5% VO2peak, day two: 70.0 ± 3.2% VO2max (mean ± SD)) at the beginning of days one and two. Across each day appetite perceptions were assessed using visual analogue scales and appetite regulatory hormones were measured from venous blood samples. Ad libitum energy and macronutrient intakes were determined from meals provided two and six hours into each day and from a snack bag provided in-between trial days. Exercise elicited a high level of energy expenditure (total = 7566 ± 635 kJ across the two days) but did not produce compensatory changes in appetite or energy intake over two days (control: 29,217 ± 4006 kJ; exercise: 28,532 ± 3899 kJ, P > 0.050). Two-way repeated measures ANOVA did not reveal any main effects for acylated ghrelin or leptin (all P > 0.050). However a significant main effect of trial (P = 0.029) for PYY indicated higher concentrations on the exercise vs. control trial. These findings suggest that across a two day period, high volume exercise does not stimulate compensatory appetite regulatory changes. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Genetic basis of nitrogen use efficiency and yield stability across environments in winter rapeseed.

PubMed

Bouchet, Anne-Sophie; Laperche, Anne; Bissuel-Belaygue, Christine; Baron, Cécile; Morice, Jérôme; Rousseau-Gueutin, Mathieu; Dheu, Jean-Eric; George, Pierre; Pinochet, Xavier; Foubert, Thomas; Maes, Olivier; Dugué, Damien; Guinot, Florent; Nesi, Nathalie

2016-09-15

Nitrogen use efficiency is an important breeding trait that can be modified to improve the sustainability of many crop species used in agriculture. Rapeseed is a major oil crop with low nitrogen use efficiency, making its production highly dependent on nitrogen input. This complex trait is suspected to be sensitive to genotype × environment interactions, especially genotype × nitrogen interactions. Therefore, phenotyping diverse rapeseed populations under a dense network of trials is a powerful approach to study nitrogen use efficiency in this crop. The present study aimed to determine the quantitative trait loci (QTL) associated with yield in winter oilseed rape and to assess the stability of these regions under contrasting nitrogen conditions for the purpose of increasing nitrogen use efficiency. Genome-wide association studies and linkage analyses were performed on two diversity sets and two doubled-haploid populations. These populations were densely genotyped, and yield-related traits were scored in a multi-environment design including seven French locations, six growing seasons (2009 to 2014) and two nitrogen nutrition levels (optimal versus limited). Very few genotype × nitrogen interactions were detected, and a large proportion of the QTL were stable across nitrogen nutrition conditions. In contrast, strong genotype × trial interactions in which most of the QTL were specific to a single trial were found. To obtain further insight into the QTL × environment interactions, genetic analyses of ecovalence were performed to identify the genomic regions contributing to the genotype × nitrogen and genotype × trial interactions. Fifty-one critical genomic regions contributing to the additive genetic control of yield-associated traits were identified, and the structural organization of these regions in the genome was investigated. Our results demonstrated that the effect of the trial was greater than the effect of nitrogen nutrition levels on seed yield-related traits under our experimental conditions. Nevertheless, critical genomic regions associated with yield that were stable across environments were identified in rapeseed.

Predictors of Outcome in Conservative and Minimally Invasive Surgical Management of Pain Originating From the Sacroiliac Joint

PubMed Central

Dengler, Julius; Duhon, Bradley; Whang, Peter; Frank, Clay; Glaser, John; Sturesson, Bengt; Garfin, Steven; Cher, Daniel; Rendahl, Aaron; Polly, David

2017-01-01

Study Design. A pooled patient-level analysis of two multicenter randomized controlled trials and one multicenter single-arm prospective trial. Objective. The aim of this study was to identify predictors of outcome of conservative and minimally invasive surgical management of pain originating from the sacroiliac joint (SIJ). Summary of Background Data. Three recently published prospective trials have shown that minimally invasive SIJ fusion (SIJF) using triangular titanium implants produces better outcomes than conservative management for patients with pain originating from the SIJ. Due to limitations in individual trial sample size, analyses of predictors of treatment outcome were not conducted. Methods. We pooled individual patient data from the three trials and used random effects models with multivariate regression analysis to identify predictors for treatment outcome separately for conservative and minimally invasive surgical treatment. Outcome was measured using visual analogue scale (VAS), Oswestry Disability Index (ODI), and EuroQOL-5D (EQ-5D). Results. We included 423 patients assigned to either nonsurgical management (NSM, n = 97) or SIJF (n = 326) between 2013 and 2015. The reduction in SIJ pain was 37.9 points larger [95% confidence interval (95% CI) 32.5–43.4, P < 0.0001] in the SIJF group than in the NSM group. Similarly, the improvement in ODI was 18.3 points larger (95% CI 14.3–22.4), P < 0.0001). In NSM, we found no predictors of outcome. In SIJF, a reduced improvement in outcome was predicted by smoking (P = 0.030), opioid use (P = 0.017), lower patient age (P = 0.008), and lower duration of SIJ pain (P = 0.028). Conclusions. Our results support the view that SIJF leads to better treatment outcome than conservative management of SIJ pain and that a higher margin of improvement can be predicted in nonsmokers, nonopioid users, and patients of increased age and with longer pain duration. Level of Evidence: 1 PMID:28350586

Development of Methods for Cross-Sectional HIV Incidence Estimation in a Large, Community Randomized Trial

PubMed Central

Donnell, Deborah; Komárek, Arnošt; Omelka, Marek; Mullis, Caroline E.; Szekeres, Greg; Piwowar-Manning, Estelle; Fiamma, Agnes; Gray, Ronald H.; Lutalo, Tom; Morrison, Charles S.; Salata, Robert A.; Chipato, Tsungai; Celum, Connie; Kahle, Erin M.; Taha, Taha E.; Kumwenda, Newton I.; Karim, Quarraisha Abdool; Naranbhai, Vivek; Lingappa, Jairam R.; Sweat, Michael D.; Coates, Thomas; Eshleman, Susan H.

2013-01-01

Background Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment. Methods and Findings Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept. Conclusions In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation. PMID:24236054

Decomposing delta, theta, and alpha time–frequency ERP activity from a visual oddball task using PCA

PubMed Central

Bernat, Edward M.; Malone, Stephen M.; Williams, William J.; Patrick, Christopher J.; Iacono, William G.

2008-01-01

Objective Time–frequency (TF) analysis has become an important tool for assessing electrical and magnetic brain activity from event-related paradigms. In electrical potential data, theta and delta activities have been shown to underlie P300 activity, and alpha has been shown to be inhibited during P300 activity. Measures of delta, theta, and alpha activity are commonly taken from TF surfaces. However, methods for extracting relevant activity do not commonly go beyond taking means of windows on the surface, analogous to measuring activity within a defined P300 window in time-only signal representations. The current objective was to use a data driven method to derive relevant TF components from event-related potential data from a large number of participants in an oddball paradigm. Methods A recently developed PCA approach was employed to extract TF components [Bernat, E. M., Williams, W. J., and Gehring, W. J. (2005). Decomposing ERP time-frequency energy using PCA. Clin Neurophysiol, 116(6), 1314–1334] from an ERP dataset of 2068 17 year olds (979 males). TF activity was taken from both individual trials and condition averages. Activity including frequencies ranging from 0 to 14 Hz and time ranging from stimulus onset to 1312.5 ms were decomposed. Results A coordinated set of time–frequency events was apparent across the decompositions. Similar TF components representing earlier theta followed by delta were extracted from both individual trials and averaged data. Alpha activity, as predicted, was apparent only when time–frequency surfaces were generated from trial level data, and was characterized by a reduction during the P300. Conclusions Theta, delta, and alpha activities were extracted with predictable time-courses. Notably, this approach was effective at characterizing data from a single-electrode. Finally, decomposition of TF data generated from individual trials and condition averages produced similar results, but with predictable differences. Specifically, trial level data evidenced more and more varied theta measures, and accounted for less overall variance. PMID:17027110

Cardiovascular rehabilitation soon after stroke using feedback-controlled robotics-assisted treadmill exercise: study protocol of a randomised controlled pilot trial.

PubMed

Stoller, Oliver; de Bruin, Eling D; Schuster-Amft, Corina; Schindelholz, Matthias; de Bie, Rob A; Hunt, Kenneth J

2013-09-22

After experiencing a stroke, most individuals also suffer from cardiac disease, are immobile and thus have low endurance for exercise. Aerobic capacity is seriously reduced in these individuals and does not reach reasonable levels after conventional rehabilitation programmes. Cardiovascular exercise is beneficial for improvement of aerobic capacity in mild to moderate stroke. However, less is known about its impact on aerobic capacity, motor recovery, and quality-of-life in severely impaired individuals. The aim of this pilot study is to explore the clinical efficacy and feasibility of cardiovascular exercise with regard to aerobic capacity, motor recovery, and quality-of-life using feedback-controlled robotics-assisted treadmill exercise in non-ambulatory individuals soon after experiencing a stroke. This will be a single-centred single blind, randomised control trial with a pre-post intervention design. Subjects will be recruited early after their first stroke (≤20 weeks) at a neurological rehabilitation clinic and will be randomly allocated to an inpatient cardiovascular exercise programme that uses feedback-controlled robotics-assisted treadmill exercise (experimental) or to conventional robotics-assisted treadmill exercise (control). Intervention duration depends on the duration of each subject's inpatient rehabilitation period. Aerobic capacity, as the primary outcome measure, will be assessed using feedback-controlled robotics-assisted treadmill-based cardiopulmonary exercise testing. Secondary outcome measures will include gait speed, walking endurance, standing function, and quality-of-life. Outcome assessment will be conducted at baseline, after each 4-week intervention period, and before clinical discharge. Ethical approval has been obtained. Whether cardiovascular exercise in non-ambulatory individuals early after stroke has an impact on aerobic capacity, motor recovery, and quality-of-life is not yet known. Feedback-controlled robotics-assisted treadmill exercise is a relatively recent intervention method and might be used to train and evaluate aerobic capacity in this population. The present pilot trial is expected to provide new insights into the implementation of early cardiovascular exercise for individuals with severe motor impairment. The findings of this study may guide future research to explore the effects of early cardiovascular activation after severe neurological events. This trial is registered with the Clinical Trials.gov Registry (NCT01679600).

Artificial bee colony algorithm for single-trial electroencephalogram analysis.

PubMed

Hsu, Wei-Yen; Hu, Ya-Ping

2015-04-01

In this study, we propose an analysis system combined with feature selection to further improve the classification accuracy of single-trial electroencephalogram (EEG) data. Acquiring event-related brain potential data from the sensorimotor cortices, the system comprises artifact and background noise removal, feature extraction, feature selection, and feature classification. First, the artifacts and background noise are removed automatically by means of independent component analysis and surface Laplacian filter, respectively. Several potential features, such as band power, autoregressive model, and coherence and phase-locking value, are then extracted for subsequent classification. Next, artificial bee colony (ABC) algorithm is used to select features from the aforementioned feature combination. Finally, selected subfeatures are classified by support vector machine. Comparing with and without artifact removal and feature selection, using a genetic algorithm on single-trial EEG data for 6 subjects, the results indicate that the proposed system is promising and suitable for brain-computer interface applications. © EEG and Clinical Neuroscience Society (ECNS) 2014.

LIMO EEG: a toolbox for hierarchical LInear MOdeling of ElectroEncephaloGraphic data.

PubMed

Pernet, Cyril R; Chauveau, Nicolas; Gaspar, Carl; Rousselet, Guillaume A

2011-01-01

Magnetic- and electric-evoked brain responses have traditionally been analyzed by comparing the peaks or mean amplitudes of signals from selected channels and averaged across trials. More recently, tools have been developed to investigate single trial response variability (e.g., EEGLAB) and to test differences between averaged evoked responses over the entire scalp and time dimensions (e.g., SPM, Fieldtrip). LIMO EEG is a Matlab toolbox (EEGLAB compatible) to analyse evoked responses over all space and time dimensions, while accounting for single trial variability using a simple hierarchical linear modelling of the data. In addition, LIMO EEG provides robust parametric tests, therefore providing a new and complementary tool in the analysis of neural evoked responses.

LIMO EEG: A Toolbox for Hierarchical LInear MOdeling of ElectroEncephaloGraphic Data

PubMed Central

Pernet, Cyril R.; Chauveau, Nicolas; Gaspar, Carl; Rousselet, Guillaume A.

2011-01-01

Magnetic- and electric-evoked brain responses have traditionally been analyzed by comparing the peaks or mean amplitudes of signals from selected channels and averaged across trials. More recently, tools have been developed to investigate single trial response variability (e.g., EEGLAB) and to test differences between averaged evoked responses over the entire scalp and time dimensions (e.g., SPM, Fieldtrip). LIMO EEG is a Matlab toolbox (EEGLAB compatible) to analyse evoked responses over all space and time dimensions, while accounting for single trial variability using a simple hierarchical linear modelling of the data. In addition, LIMO EEG provides robust parametric tests, therefore providing a new and complementary tool in the analysis of neural evoked responses. PMID:21403915

Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B

PubMed Central

Nathwani, A.C.; Reiss, U.M.; Tuddenham, E.G.D.; Rosales, C.; Chowdary, P.; McIntosh, J.; Della Peruta, M.; Lheriteau, E.; Patel, N.; Raj, D.; Riddell, A.; Pie, J.; Rangarajan, S.; Bevan, D.; Recht, M.; Shen, Y.-M.; Halka, K.G.; Basner-Tschakarjan, E.; Mingozzi, F.; High, K.A.; Allay, J.; Kay, M.A.; Ng, C.Y.C.; Zhou, J.; Cancio, M.; Morton, C.L.; Gray, J.T.; Srivastava, D.; Nienhuis, A.W.; Davidoff, A.M.

2014-01-01

BACKGROUND In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose–response relationship, and the level of persistent or late toxicity. METHODS We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×1012 vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. RESULTS A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. CONCLUSIONS In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00979238.) PMID:25409372

Learning and mastery behaviours as risk factors to abandonment in a paediatric user of advanced single-switch access technology.

PubMed

Brian, Leung; Jessica A, Brian; Tom, Chau

2013-09-01

The present descriptive case study documents the behaviours of a child single-switch user in the community setting and draws attention to learning and mastery behaviours as risk factors to single-switch abandonment. Our observations were interpreted in the context of a longer term school-based evaluation of an advanced single-switch access technology with a nine year-old user with severe spastic quadriplegic cerebral palsy. The child completed 25 experiment sessions averaging a rate of three sessions every two weeks. During each session he worked on several blocks of single-switch computer activity using his vocal cord vibration switch. Despite high levels of single-switch sensitivity and specificity that suggested a good fit between the participant and the technology, the participant perceived a lower proficiency level of his own abilities, demonstrated impatience and intolerance to interaction errors, and was apprehensive of making mistakes when using his switch in public. The benefit of gaining some degree of independent physical access might not necessarily enhance resilience to interaction errors or bouts of poor task performance. On the other hand, the participant's behaviours were consistent with those of a typically developing child learning or mastering any new skill or task. Implications for Rehabilitation The attitude and behaviour of a paediatric switch user towards skill development can be risk factors to abandonment of an access technology, despite successful clinical trial with the device. Children with severe disabilities can be associated with the same types of skill development behaviour patterns and achievement motivation as their typically developing peers. Empirical observations of the case participant's switch use behaviours suggest that user training could be adaptive in order to account for individual differences in skill development and achievement motivation.

No difference in terms of radiostereometric analysis between fixed- and mobile-bearing total knee arthroplasty: a randomized, single-blind, controlled trial.

PubMed

Schotanus, M G M; Pilot, P; Kaptein, B L; Draijer, W F; Tilman, P B J; Vos, R; Kort, N P

2017-09-01

A concern that arises with any new prosthesis is whether it will achieve satisfactory long-term implant stability. The gold standard of assessing the quality of fixation in a new or relatively new implant is to undertake a randomized controlled trial using radiostereometric analysis. It was hypothesized that both mobile-bearing total knee arthroplasty and fixed-bearing total knee arthroplasty have comparable migration patterns at 2-year follow-up. This study investigated two types of cemented total knee arthroplasty, the mobile- or fixed-bearing variant from the same family with use of radiostereometric analysis. This prospective, patient-blinded, randomized, controlled trial was designed to investigate early migration of the tibia component after two years of follow-up with use of radiostereometric analysis. A total of 50 patients were randomized to receive a mobile- or fixed-bearing TKA from the same family. Patients were evaluated during 2-year follow-up, including radiostereometric analysis, physical and clinical examination and patient reported outcome measures (PROMs). At two-year follow-up, the mean (±SD) maximum total point motion (MTPM) in the fixed-bearing group was 0.82 (±1.16) versus 0.92 mm (±0.64) in the mobile-bearing group (p = n.s) with the largest migration seen during the first 6 weeks (0.45 ± 0.32 vs. 0.54 ± 0.30). The clinical outcome and PROMs significantly improved within each group, not between both groups. Measuring early micromotion is useful for predicting clinical loosening that can lead to revision. The results of this study demonstrate that early migration of the mobile-bearing is similar to that of the fixed-bearing component at two years and was mainly seen in the first weeks after implantation. Randomized, single-blind, controlled trial, Level I.

Cumulative recruitment experience in two large single-center randomized, controlled clinical trials.

PubMed

Galbreath, Autumn Dawn; Smith, Brad; Wood, Pamela; Forkner, Emma; Peters, Jay I

2008-05-01

Trial recruitment is challenging for researchers, who frequently overestimate the pool of qualified, willing participants. Little has been written about recruitment and the comparative success of recruitment strategies. We describe one center's experience with recruitment in two regional single-center clinical trials with a combined total of 1971 participants. The heart failure trial was conducted between 1999 and 2003. The asthma trial was performed between 2003 and 2006. Trial databases were queried for referral source of each individual. Data were analyzed for effectiveness of referral source using three measures: percentage of enrollment due to that source, subject commitment to the trial (retention rate), and economics (cost per enrollee). 47.8% of CHF enrollees came from computer-generated lists or from healthcare provider referrals. Average marketing cost for enrollees and completers was $29.20 and $41.96 respectively. The most economical marketing strategy was self-referral in response to flyers. Most asthma participants (53.5%) were referred from healthcare providers, mailings to lists from local healthcare institutions, or self-referred in response to flyers. Average marketing cost for enrollees and completers was $20.44 and $38.10 respectively. The most economical marketing strategy was patient mailings. Retention rates were not markedly different among referral sources in either trial. In order to be considered effective, a recruitment strategy must demonstrate a balance between response to recruitment, retention rates, and economics. Despite the differences between these two clinical trials, the most effective recruitment strategies in both trials were mailings to locally-generated, targeted lists, and referrals from healthcare providers.

Anterior surgical management of single-level cervical disc disease: a cost-effectiveness analysis.

PubMed

Lewis, Daniel J; Attiah, Mark A; Malhotra, Neil R; Burnett, Mark G; Stein, Sherman C

2014-12-01

Cost-effectiveness analysis with decision analysis and meta-analysis. To determine the relative cost-effectiveness of anterior cervical discectomy with fusion (with autograft, allograft, or spacers), anterior cervical discectomy without fusion (ACD), and cervical disc replacement (CDR) for the treatment of 1-level cervical disc disease. There is debate as to the optimal anterior surgical strategy to treat single-level cervical disc disease. Surgical strategies include 3 techniques of anterior cervical discectomy with fusion (autograft, allograft, or spacer-assisted fusion), ACD, and CDR. Several controlled trials have compared these treatments but have yielded mixed results. Decision analysis provides a structure for making a quantitative comparison of the costs and outcomes of each treatment. A literature search was performed and yielded 156 case series that fulfilled our search criteria describing nearly 17,000 cases. Data were abstracted from these publications and pooled meta-analytically to estimate the incidence of various outcomes, including index-level and adjacent-level reoperation. A decision analytic model calculated the expected costs in US dollars and outcomes in quality-adjusted life years for a typical adult patient with 1-level cervical radiculopathy subjected to each of the 5 approaches. At 5 years postoperatively, patients who had undergone ACD alone had significantly (P < 0.001) more quality-adjusted life years (4.885 ± 0.041) than those receiving other treatments. Patients with ACD also exhibited highly significant (P < 0.001) differences in costs, incurring the lowest societal costs ($16,558 ± $539). Follow-up data were inadequate for comparison beyond 5 years. The results of our decision analytic model indicate advantages for ACD, both in effectiveness and costs, over other strategies. Thus, ACD is a cost-effective alternative to anterior cervical discectomy with fusion and CDR in patients with single-level cervical disc disease. Definitive conclusions about degenerative changes after ACD and adjacent-level disease after CDR await longer follow-up. 4.

The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments on Schistosoma mansoni Infections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

PubMed Central

Buza, Joram; Mpolya, Emmanuel A.; Angelo, Teckla; Kinung'hi, Safari M.

2017-01-01

Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p < 0.001). The egg reduction rate was higher on repeated dose (97.54%) compared to single dose (87.27%) (p = 0.0062). Geometric mean egg intensity was lower among those on repeated dose (1.30 epg) compared to single dose (3.18 epg) (p = 0.036) but not at 5 (p > 0.05) and 8 (p > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p < 0.001). There was an increase in the mean haemoglobin levels at 8 months with no difference between the two arms (p > 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered with PACTR201601001416338. PMID:29094048

Cardiovascular rehabilitation soon after stroke using feedback-controlled robotics-assisted treadmill exercise: study protocol of a randomised controlled pilot trial

PubMed Central

2013-01-01

Background After experiencing a stroke, most individuals also suffer from cardiac disease, are immobile and thus have low endurance for exercise. Aerobic capacity is seriously reduced in these individuals and does not reach reasonable levels after conventional rehabilitation programmes. Cardiovascular exercise is beneficial for improvement of aerobic capacity in mild to moderate stroke. However, less is known about its impact on aerobic capacity, motor recovery, and quality-of-life in severely impaired individuals. The aim of this pilot study is to explore the clinical efficacy and feasibility of cardiovascular exercise with regard to aerobic capacity, motor recovery, and quality-of-life using feedback-controlled robotics-assisted treadmill exercise in non-ambulatory individuals soon after experiencing a stroke. Methods/Design This will be a single-centred single blind, randomised control trial with a pre-post intervention design. Subjects will be recruited early after their first stroke (≤20 weeks) at a neurological rehabilitation clinic and will be randomly allocated to an inpatient cardiovascular exercise programme that uses feedback-controlled robotics-assisted treadmill exercise (experimental) or to conventional robotics-assisted treadmill exercise (control). Intervention duration depends on the duration of each subject’s inpatient rehabilitation period. Aerobic capacity, as the primary outcome measure, will be assessed using feedback-controlled robotics-assisted treadmill-based cardiopulmonary exercise testing. Secondary outcome measures will include gait speed, walking endurance, standing function, and quality-of-life. Outcome assessment will be conducted at baseline, after each 4-week intervention period, and before clinical discharge. Ethical approval has been obtained. Discussion Whether cardiovascular exercise in non-ambulatory individuals early after stroke has an impact on aerobic capacity, motor recovery, and quality-of-life is not yet known. Feedback-controlled robotics-assisted treadmill exercise is a relatively recent intervention method and might be used to train and evaluate aerobic capacity in this population. The present pilot trial is expected to provide new insights into the implementation of early cardiovascular exercise for individuals with severe motor impairment. The findings of this study may guide future research to explore the effects of early cardiovascular activation after severe neurological events. Trial registration This trial is registered with the Clinical Trials.gov Registry (NCT01679600). PMID:24053609

Single-trial event-related potentials to significant stimuli.

PubMed

Rushby, Jacqueline A; Barry, Robert J

2009-11-01

The stimulus-response pattern of the skin conductance response (SCR) was used as a model of the Orienting Reflex (OR) to assess the P1, N1, P2, N2 and late positive complex (LPC/P300) components of the ERP in a simple habituation paradigm, in which a single series of 12 innocuous tones were presented at a very long interstimulus interval (2 min). To maintain their waking state during this boring task, participants were instructed to alternately close or open their eyes to each stimulus. None of the baseline-to-peak ERP measures showed trials effects comparable with the marked habituation over trials shown by the SCRs. Principal Components Analysis was used to decompose the ERP, yielding factors identified as the N1, N2, P3a, P3b and Novelty P3 components. An additional factor represented later eye-movement activity. No trial effects were apparent for the N1, N2, P3a or P3b components. The Novelty P3 showed marked response decrement over trials. These results are discussed in relation to current conceptualisations of the OR.

Single-Incision Multiport/Single Port Laparoscopic Abdominal Surgery (SILAP): A Prospective Multicenter Observational Quality Study.

PubMed

Mantke, Rene; Diener, Markus; Kropf, Siegfried; Otto, Ronny; Manger, Thomas; Vestweber, Boris; Mirow, Lutz; Winde, Günther; Lippert, Hans

2016-09-07

Increasing experience with minimally invasive surgery and the development of new instruments has resulted in a tendency toward reducing the number of abdominal skin incisions. Retrospective and randomized prospective studies could show the feasibility of single-incision surgery without any increased risk to the patient. However, large prospective multicenter observational datasets do not currently exist. This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. This study focuses on external validity, clinical relevance, and the patients' perspective. Accordingly, the single-incision multiport/single port laparoscopic abdominal surgery (SILAP) study will supplement the existing evidence, which does not currently allow evidence-based surgical decision making. The SILAP study is an international prospective multicenter observational quality study. Mortality, morbidity, complications during surgery, complications postoperatively, patient characteristics, and technical aspects will be monitored. We expect more than 100 surgical centers to participate with 5000 patients with abdominal single-incision surgery during the study period. Funding was obtained in 2012. Enrollment began on January 01, 2013, and will be completed on December 31, 2018. As of January 2016, 2119 patients have been included, 106 German centers are registered, and 27 centers are very active (>5 patients per year). This prospective multicenter observational quality study will provide a relevant dataset reflecting the feasibility and safety of single-incision surgery. An international enlargement and recruitment of centers outside of Germany is meaningful. German Clinical Trials Register: DRKS00004594; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004594 (Archived by WebCite at http://www.webcitation.org/6jK6ZVyUs).

Retroactive interference in short-term memory and the word-length effect.

PubMed

Campoy, Guillermo

2011-09-01

Two experiments investigated the possibility that the word-length effect in short-term memory (STM) is a consequence of long words generating a greater level of retroactive interference than shorter words. In Experiment 1, six-word lists were auditorily presented under articulatory suppression for immediate serial reconstruction of only the first three words. These three words were always drawn from a single set of middle-length words, whereas the last three positions were occupied by either short or long interfering words. The results showed worse memory performance when the to-be-remembered words were followed by long words. In Experiment 2, a recent-probes task was used, in which recent negative probes matched a target word in trial n-2. The results showed lower levels of proactive interference when trial n-1 involved long words instead of short words, suggesting that long words displaced previous STM content to a greater extent. By two different experimental approaches, therefore, this study shows that long words produce more retroactive interference than short words, supporting an interference-based account for the word-length effect. Copyright © 2011 Elsevier B.V. All rights reserved.

Across-channel interference in intensity discrimination: The role of practice and listening strategy

PubMed Central

Buss, Emily

2008-01-01

Pure tone intensity discrimination thresholds can be elevated by the introduction of remote maskers with roved level. This effect is on the order of 10 dB [10log(ΔI/I)] in some conditions and can be demonstrated under conditions of little or no energetic masking. The current study examined the effect of practice and observer strategy on this phenomenon. Experiment 1 included observers who had no formal experience with intensity discrimination and provided training over six hours on a single masked intensity discrimination task to assess learning effects. Thresholds fell with practice for most observers, with significant improvements in 6 out of 8 cases. Despite these improvements significant masking remained in all cases. The second experiment assessed trial-by-trial effects of roved masker level. Conditional probability of a ‘signal-present’ response as a function of the rove value assigned to each of the two masker tones indicates fundamental differences among observers’ processing strategies, even after six hours of practice. The variability in error patterns across practiced listeners suggests that observers approach the task differently, though this variability does not appear to be related to sensitivity. PMID:18177156