Distinct Effects of Trial-Driven and Task Set-Related Control in Primary Visual Cortex

PubMed Central

Vaden, Ryan J.; Visscher, Kristina M.

2015-01-01

Task sets are task-specific configurations of cognitive processes that facilitate task-appropriate reactions to stimuli. While it is established that the trial-by-trial deployment of visual attention to expected stimuli influences neural responses in primary visual cortex (V1) in a retinotopically specific manner, it is not clear whether the mechanisms that help maintain a task set over many trials also operate with similar retinotopic specificity. Here, we address this question by using BOLD fMRI to characterize how portions of V1 that are specialized for different eccentricities respond during distinct components of an attention-demanding discrimination task: cue-driven preparation for a trial, trial-driven processing, task-initiation at the beginning of a block of trials, and task-maintenance throughout a block of trials. Tasks required either unimodal attention to an auditory or a visual stimulus or selective intermodal attention to the visual or auditory component of simultaneously presented visual and auditory stimuli. We found that while the retinotopic patterns of trial-driven and cue-driven activity depended on the attended stimulus, the retinotopic patterns of task-initiation and task-maintenance activity did not. Further, only the retinotopic patterns of trial-driven activity were found to depend on the presence of intermodal distraction. Participants who performed well on the intermodal selective attention tasks showed strong task-specific modulations of both trial-driven and task-maintenance activity. Importantly, task-related modulations of trial-driven and task-maintenance activity were in opposite directions. Together, these results confirm that there are (at least) two different processes for top-down control of V1: One, working trial-by-trial, differently modulates activity across different eccentricity sectors—portions of V1 corresponding to different visual eccentricities. The second process works across longer epochs of task performance, and does not differ among eccentricity sectors. These results are discussed in the context of previous literature examining top-down control of visual cortical areas. PMID:26163806

Emerging Trends in the Management of Brain Metastases from Non-small Cell Lung Cancer.

PubMed

Churilla, Thomas M; Weiss, Stephanie E

2018-05-07

To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC). Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1-4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity. Current brain metastasis trials are focused on reducing cognitive toxicity: hippocampal sparing WBRT, SRS for 5-15 metastases, pre-operative SRS, and use of systemic targeted agents or immunotherapy. The role for radiotherapy in the management of brain metastases is becoming better defined with local treatment shifting from WBRT to SRS alone for limited brain metastases and post-operative SRS for resected metastases. Further trials are warranted to define the optimal integration of newer systemic agents with local therapies.

A randomized clinical trial of how to best position retropubic slings for stress urinary incontinence: Development of a study protocol for the mid-urethral sling tensioning (MUST) trial.

PubMed

Brennand, Erin A; Kim-Fine, Shunaha

2016-08-15

The goal of this trial is to compare two techniques for tensioning retropubic midurethral slings: a Mayo scissor between the tape and urethra vs. a Babcock clamp creating a measured loop underneath the urethra. The primary outcome is a composite of abnormal bladder function at 12 months post surgery. Abnormal bladder function is defined as bothersome stress incontinence or worsening over active bladder symptoms, a positive cough stress test, re-treatment of stress urinary incontinence, post-operative urinary retention requiring either catheterization beyond 6 weeks or surgical intervention. Secondary outcomes include the duration of post operative urinary retention, quality of life scores, and physical examination. This article describes the rationale and design of this clinical trial, which will be of interest to those who care for patient with pelvic floor disorders such as stress urinary incontinence.

Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials.

PubMed

Hindryckx, Pieter; Levesque, Barrett G; Holvoet, Tom; Durand, Serina; Tang, Ceen-Ming; Parker, Claire; Khanna, Reena; Shackelton, Lisa M; D'Haens, Geert; Sandborn, William J; Feagan, Brian G; Lebwohl, Benjamin; Leffler, Daniel A; Jairath, Vipul

2018-01-01

Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials. MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA). Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy. Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development. 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/.

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

PubMed

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

2015-06-01

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

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

PubMed

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

2016-05-01

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

A BEFORE AND AFTER TRIAL OF THE EFFECTIVENESS OF NETWORK ANALYSIS IN HEALTH OPERATIONS MANAGEMENT.

PubMed

Bhalwar, R; Srivastava, M; Verma, S S; Vaze, M; Tilak, V W

1996-10-01

An intervention trial using "before-and-after" approach was undertaken to address the question whether network analysis as a health managerial tool of control can favourably affect the delays that occur in planning and executing the antimalaria operations of a Station Health Organization in a large military station. Exposure variable of interest was intervention with a network diagram, by which the potential causes of delay along the various activities were assessed and remedial measures were introduced during the second year. Sample size was calculated using conventional alpha and beta error levels. The study indicated that there was a definite beneficial outcome in that the operations could be started as well as completed in time during the intervention year. There was reduction in time requirement in 5 out of the 9 activities, the exact 'p' value being 0.08, by both parametric and non-parametric tests. The use of network analysis in health care management has been recommended.

Who's really hypertensive?--Quality control issues in the assessment of blood pressure for randomized trials.

PubMed

Reid, Christopher M; Ryan, Philip; Miles, Helen; Willson, Kristyn; Beilin, Laurence J; Brown, Mark A; Jennings, Garry L; Johnston, Colin I; Macdonald, Graham J; Marley, John E; McNeil, John J; Morgan, Trefor O; West, Malcolm J; Wing, Lindon M H

2005-01-01

The characterization of blood pressure in treatment trials assessing the benefits of blood pressure lowering regimens is a critical factor for the appropriate interpretation of study results. With numerous operators involved in the measurement of blood pressure in many thousands of patients being screened for entry into clinical trials, it is essential that operators follow pre-defined measurement protocols involving multiple measurements and standardized techniques. Blood pressure measurement protocols have been developed by international societies and emphasize the importance of appropriate choice of cuff size, identification of Korotkoff sounds, and digit preference. Training of operators and auditing of blood pressure measurement may assist in reducing the operator-related errors in measurement. This paper describes the quality control activities adopted for the screening stage of the 2nd Australian National Blood Pressure Study (ANBP2). ANBP2 is cardiovascular outcome trial of the treatment of hypertension in the elderly that was conducted entirely in general practices in Australia. A total of 54 288 subjects were screened; 3688 previously untreated subjects were identified as having blood pressure >140/90 mmHg at the initial screening visit, 898 (24%) were not eligible for study entry after two further visits due to the elevated reading not being sustained. For both systolic and diastolic blood pressure recording, observed digit preference fell within 7 percentage points of the expected frequency. Protocol adherence, in terms of the required minimum blood pressure difference between the last two successive recordings, was 99.8%. These data suggest that adherence to blood pressure recording protocols and elimination of digit preferences can be achieved through appropriate training programs and quality control activities in large multi-centre community-based trials in general practice. Repeated blood pressure measurement prior to initial diagnosis and study entry is essential to appropriately characterize hypertension in these elderly patients.

Function after spinal treatment, exercise and rehabilitation (FASTER): improving the functional outcome of spinal surgery.

PubMed

McGregor, A H; Doré, C J; Morris, T P; Morris, S; Jamrozik, K

2010-01-26

The life-time incidence of low back pain is high and diagnoses of spinal stenosis and disc prolapse are increasing. Consequently, there is a steady rise in surgical interventions for these conditions. Current evidence suggests that while the success of surgery is incomplete, it is superior to conservative interventions. A recent survey indicates that there are large differences in the type and intensity of rehabilitation, if any, provided after spinal surgery as well as in the restrictions and advice given to patients in the post-operative period. This trial will test the hypothesis that functional outcome following two common spinal operations can be improved by a programme of post-operative rehabilitation that combines professional support and advice with graded active exercise and/or an educational booklet based on evidence-based messages and advice. The study design is a multi-centre, factorial, randomised controlled trial with patients stratified by surgeon and operative procedure. The trial will compare the effectiveness and cost-effectiveness of a rehabilitation programme and an education booklet for the postoperative management of patients undergoing discectomy or lateral nerve root decompression, each compared with "usual care"using a 2 x 2 factorial design. The trial will create 4 sub-groups; rehabilitation-only, booklet-only, rehabilitation-plus-booklet, and usual care only. The trial aims to recruit 344 patients, which equates to 86 patients in each of the four sub-groups. All patients will be assessed for functional ability (through the Oswestry Disability Index - a disease specific functional questionnaire), pain (using visual analogue scales), and satisfaction pre-operatively and then at 6 weeks, 3, 6 and 9 months and 1 year post-operatively. This will be complemented by a formal analysis of cost-effectiveness. This trial will determine whether the outcome of spinal surgery can be enhanced by either a post-operative rehabilitation programme or an evidence-based advice booklet or a combination of the two and as such will contribute to our knowledge on how to manage spinal surgery patients in the post-operative period.

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.

Trial-by-Trial Changes in a Priori Informational Value of External Cues and Subjective Expectancies in Human Auditory Attention

PubMed Central

Arjona, Antonio; Gómez, Carlos M.

2011-01-01

Background Preparatory activity based on a priori probabilities generated in previous trials and subjective expectancies would produce an attentional bias. However, preparation can be correct (valid) or incorrect (invalid) depending on the actual target stimulus. The alternation effect refers to the subjective expectancy that a target will not be repeated in the same position, causing RTs to increase if the target location is repeated. The present experiment, using the Posner's central cue paradigm, tries to demonstrate that not only the credibility of the cue, but also the expectancy about the next position of the target are changedin a trial by trial basis. Sequences of trials were analyzed. Results The results indicated an increase in RT benefits when sequences of two and three valid trials occurred. The analysis of errors indicated an increase in anticipatory behavior which grows as the number of valid trials is increased. On the other hand, there was also an RT benefit when a trial was preceded by trials in which the position of the target changed with respect to the current trial (alternation effect). Sequences of two alternations or two repetitions were faster than sequences of trials in which a pattern of repetition or alternation is broken. Conclusions Taken together, these results suggest that in Posner's central cue paradigm, and with regard to the anticipatory activity, the credibility of the external cue and of the endogenously anticipated patterns of target location are constantly updated. The results suggest that Bayesian rules are operating in the generation of anticipatory activity as a function of the previous trial's outcome, but also on biases or prior beliefs like the “gambler fallacy”. PMID:21698164

Sustainability and performance of the National Cancer Institute’s Community Clinical Oncology Program

PubMed Central

Carpenter, William R.; Fortune-Greeley, Alice K.; Zullig, Leah L.; Lee, Shoou-Yih; Weiner, Bryan J.

2011-01-01

Introduction The National Cancer Institute’s (NCI) Community Clinical Oncology Program (CCOP) contributes one third of NCI treatment trial enrollment (“accrual”) and most cancer prevention and control (CP/C) trial enrollment. Prior research indicated that the local clinical environment influenced CCOP accrual performance during the 1990s. As the NCI seeks to improve the operations of the clinical trials system following critical reports by the Institute of Medicine and the NCI Operational Efficiency Working Group, the current relevance of the local environmental context on accrual performance is unknown. Materials and methods This longitudinal quasi-experimental study used panel data on 45 CCOPs nationally for years 2000–2007. Multivariable models examine organizational, research network, and environmental factors associated with accrual to treatment trials, CP/C trials, and trials overall. Results For total trial accrual and treatment trial accrual, the number of active CCOP physicians and the number of trials were associated with CCOP performance. Factors differ for CP/C trials. CCOPs in areas with fewer medical school-affiliated hospitals had greater treatment trial accrual. Conclusions Findings suggest a shift in the relevance of the clinical environment since the 1990s, as well as changes in CCOP structure associated with accrual performance. Rather than a limited number of physicians being responsible for the preponderance of trial accrual, there is a trend toward accrual among a larger number of physicians each accruing relatively fewer patients to trial. Understanding this dynamic in the context of CCOP efficiency may inform and strengthen CCOP organization and physician practice. PMID:21986391

[Effect of cellular immune supportive treatment on immunity of esophageal carcinoma patients after modern two-field lymph node dissection].

PubMed

Wang, Jun-Ye; Ma, Guo-Wei; Dai, Shu-Qin; Rong, Tie-Hua; Wang, Xin; Lin, Peng; Ye, Wen-Feng; Zhang, Lan-Jun; Li, Xiao-Dong; Zhang, Xu; Yao, Guang-Yu

2007-07-01

Cellular immunity suppression is marked in patients with esophageal carcinoma, which may be resulted temporarily from surgical injury. This study was to evaluate the effect of cellular immune supportive treatment on cellular immunity of patients with esophageal carcinoma. A total of 60 patients with thoracic esophageal carcinoma, received two-field dissection, were randomized into control group and trial (immune supportive treatment) group. The patients in trial group were injected with Shenqi injection after operation; the patients in control group received no immune supportive treatment. Peripheral blood samples were obtained before operation, and 3 and 9 days after operation. AgNOR (argyrophilic nucleolar organizer regions) activity in peripheral blood T lymphocytes was measured by tumor immune microphotometry. T cell subsets were measured by flow cytometry. The proportions of CD3+CD4+ and CD4+/CD8+ cells were significantly higher in trial group than in control group at 3 days after operation (P < 0.05). The amount of AgNOR and proportions of CD3+, CD3+CD4+, CD4+/CD8+, and CD4+CD25+ cells were significantly higher in trial group than in control group at 9 days after operation (P < 0.05). There was no significant difference in 1-year survival rate between the 2 groups (P > 0.05). Shenqi injection could obviously improve cellular immunity of the esophageal carcinoma patients after modern two-field dissection.

Activating clinical trials: a process improvement approach.

PubMed

Martinez, Diego A; Tsalatsanis, Athanasios; Yalcin, Ali; Zayas-Castro, José L; Djulbegovic, Benjamin

2016-02-24

The administrative process associated with clinical trial activation has been criticized as costly, complex, and time-consuming. Prior research has concentrated on identifying administrative barriers and proposing various solutions to reduce activation time, and consequently associated costs. Here, we expand on previous research by incorporating social network analysis and discrete-event simulation to support process improvement decision-making. We searched for all operational data associated with the administrative process of activating industry-sponsored clinical trials at the Office of Clinical Research of the University of South Florida in Tampa, Florida. We limited the search to those trials initiated and activated between July 2011 and June 2012. We described the process using value stream mapping, studied the interactions of the various process participants using social network analysis, and modeled potential process modifications using discrete-event simulation. The administrative process comprised 5 sub-processes, 30 activities, 11 decision points, 5 loops, and 8 participants. The mean activation time was 76.6 days. Rate-limiting sub-processes were those of contract and budget development. Key participants during contract and budget development were the Office of Clinical Research, sponsors, and the principal investigator. Simulation results indicate that slight increments on the number of trials, arriving to the Office of Clinical Research, would increase activation time by 11 %. Also, incrementing the efficiency of contract and budget development would reduce the activation time by 28 %. Finally, better synchronization between contract and budget development would reduce time spent on batching documentation; however, no improvements would be attained in total activation time. The presented process improvement analytic framework not only identifies administrative barriers, but also helps to devise and evaluate potential improvement scenarios. The strength of our framework lies in its system analysis approach that recognizes the stochastic duration of the activation process and the interdependence between process activities and entities.

Requirements management for Gemini Observatory: a small organization with big development projects

NASA Astrophysics Data System (ADS)

Close, Madeline; Serio, Andrew; Cordova, Martin; Hardie, Kayla

2016-08-01

Gemini Observatory is an astronomical observatory operating two premier 8m-class telescopes, one in each hemisphere. As an operational facility, a majority of Gemini's resources are spent on operations however the observatory undertakes major development projects as well. Current projects include new facility science instruments, an operational paradigm shift to full remote operations, and new operations tools for planning, configuration and change control. Three years ago, Gemini determined that a specialized requirements management tool was needed. Over the next year, the Gemini Systems Engineering Group investigated several tools, selected one for a trial period and configured it for use. Configuration activities including definition of systems engineering processes, development of a requirements framework, and assignment of project roles to tool roles. Test projects were implemented in the tool. At the conclusion of the trial, the group determined that the Gemini could meet its requirements management needs without use of a specialized requirements management tool, and the group identified a number of lessons learned which are described in the last major section of this paper. These lessons learned include how to conduct an organizational needs analysis prior to pursuing a tool; caveats concerning tool criteria and the selection process; the prerequisites and sequence of activities necessary to achieve an optimum configuration of the tool; the need for adequate staff resources and staff training; and a special note regarding organizations in transition and archiving of requirements.

Building trust and diversity in patient-centered oncology clinical trials: An integrated model.

PubMed

Hurd, Thelma C; Kaplan, Charles D; Cook, Elise D; Chilton, Janice A; Lytton, Jay S; Hawk, Ernest T; Jones, Lovell A

2017-04-01

Trust is the cornerstone of clinical trial recruitment and retention. Efforts to decrease barriers and increase clinical trial participation among diverse populations have yielded modest results. There is an urgent need to better understand the complex interactions between trust and clinical trial participation. The process of trust-building has been a focus of intense research in the business community. Yet, little has been published about trust in oncology clinical trials or the process of building trust in clinical trials. Both clinical trials and business share common dimensions. Business strategies for building trust may be transferable to the clinical trial setting. This study was conducted to understand and utilize contemporary thinking about building trust to develop an Integrated Model of Trust that incorporates both clinical and business perspectives. A key word-directed literature search of the PubMed, Medline, Cochrane, and Google Search databases for entries dated between 1 January 1985 and 1 September 2015 was conducted to obtain information from which to develop an Integrated Model of Trust. Successful trial participation requires both participants and clinical trial team members to build distinctly different types of interpersonal trust to effect recruitment and retention. They are built under conditions of significant emotional stress and time constraints among people who do not know each other and have never worked together before. Swift Trust and Traditional Trust are sequentially built during the clinical trial process. Swift trust operates during the recruitment and very early active treatment phases of the clinical trial process. Traditional trust is built over time and operates during the active treatment and surveillance stages of clinical trials. The Psychological Contract frames the participants' and clinical trial team members' interpersonal trust relationship. The "terms" of interpersonal trust are negotiated through the psychological contract. Contract renegotiation occurs in response to cyclical changes within the trust relationship throughout trial participation. The Integrated Model of Trust offers a novel framework to interrogate the process by which diverse populations and clinical trial teams build trust. To our knowledge, this is the first model of trust-building in clinical trials that frames trust development through integrated clinical and business perspectives. By focusing on the process, rather than outcomes of trust-building diverse trial participants, clinical trials teams, participants, and cancer centers may be able to better understand, measure, and manage their trust relationships in real time. Ultimately, this may foster increased recruitment and retention of diverse populations to clinical trials.

A meta-analysis of laparoscopic versus open appendectomy in patients suspected of having acute appendicitis

PubMed Central

Temple, Larissa K.F.; Litwin, Demetrius E.; McLeod, Robin S.

Objective To determine if any significant differences exist between laparoscopic appendectomy (LA) and open appendectomy (OA). Design A meta-analysis of randomized controlled trials (RCTs) comparing LA to OA. Data sources An extensive literature search was conducted for appropriate articles published between January 1990 and March 1997. Articles were initially retrieved through MEDLINE with MeSH terms “appendicitis” or “appendectomy” and “laparoscopy.” Additional methods included cross-referencing bibliographies of retrieved articles, hand searching abstracts from relevant meetings and consultation with a content expert. Study selection Only RCTs published in English in which patients had a preoperative diagnosis of acute appendicitis were included. Data extraction The outcomes of interest included operating time, hospital stay, readmission rates, return to normal activity and complications. The Cochrane Collaboration Review Manager 3.0 was used to calculate odds ratios (OR), weighted mean differences (WMD) and 95% confidence intervals (CI). The random-effects model was used for statistical analysis. Data synthesis Twelve trials met the inclusion criteria. Because there were insufficient data in some trials, operating time, hospitalization and return to work were assessed in only 8 trials. Mean operating time was significantly longer with LA (WMD 18.10 minutes, 95% CI 12.87 to 23.15 minutes). There were fewer wound infections in LA (OR 0.40, 95% CI 0.24 to 0.69), but no significant differences in intra-abdominal abscess rates (OR 1.94, 95% CI 0.68 to 5.58). There was no significant difference in the mean length of hospital stay (WMD −0.16 days, 95% CI −0.44 to 0.15 days) or readmission rates (OR 1.16, 95% CI 0.54 to 2.48). However, the return to normal activity was significantly earlier with LA (WMD −5.79 days, 95% CI −7.38 to −4.21 days). Sensitivity analyses did not affect the results. Conclusion This meta-analysis suggests that operating room time is significantly longer, hospital stay is unchanged but return to normal activities is significantly earlier with LA. PMID:10526524

Selecting promising treatments in randomized Phase II cancer trials with an active control.

PubMed

Cheung, Ying Kuen

2009-01-01

The primary objective of Phase II cancer trials is to evaluate the potential efficacy of a new regimen in terms of its antitumor activity in a given type of cancer. Due to advances in oncology therapeutics and heterogeneity in the patient population, such evaluation can be interpreted objectively only in the presence of a prospective control group of an active standard treatment. This paper deals with the design problem of Phase II selection trials in which several experimental regimens are compared to an active control, with an objective to identify an experimental arm that is more effective than the control or to declare futility if no such treatment exists. Conducting a multi-arm randomized selection trial is a useful strategy to prioritize experimental treatments for further testing when many candidates are available, but the sample size required in such a trial with an active control could raise feasibility concerns. In this study, we extend the sequential probability ratio test for normal observations to the multi-arm selection setting. The proposed methods, allowing frequent interim monitoring, offer high likelihood of early trial termination, and as such enhance enrollment feasibility. The termination and selection criteria have closed form solutions and are easy to compute with respect to any given set of error constraints. The proposed methods are applied to design a selection trial in which combinations of sorafenib and erlotinib are compared to a control group in patients with non-small-cell lung cancer using a continuous endpoint of change in tumor size. The operating characteristics of the proposed methods are compared to that of a single-stage design via simulations: The sample size requirement is reduced substantially and is feasible at an early stage of drug development.

Resource implications of preparing individual participant data from a clinical trial to share with external researchers.

PubMed

Tudur Smith, Catrin; Nevitt, Sarah; Appelbe, Duncan; Appleton, Richard; Dixon, Pete; Harrison, Janet; Marson, Anthony; Williamson, Paula; Tremain, Elizabeth

2017-07-17

Demands are increasingly being made for clinical trialists to actively share individual participant data (IPD) collected from clinical trials using responsible methods that protect the confidentiality and privacy of clinical trial participants. Clinical trialists, particularly those receiving public funding, are often concerned about the additional time and money that data-sharing activities will require, but few published empirical data are available to help inform these decisions. We sought to evaluate the activity and resources required to prepare anonymised IPD from a clinical trial in anticipation of a future data-sharing request. Data from two UK publicly funded clinical trials were used for this exercise: 2437 participants with epilepsy recruited from 90 hospital outpatient clinics in the SANAD trial and 146 children with neuro-developmental problems recruited from 18 hospitals in the MENDS trial. We calculated the time and resources required to prepare each anonymised dataset and assemble a data pack ready for sharing. The older SANAD trial (published 2007) required 50 hours of staff time with a total estimated associated cost of £3185 whilst the more recently completed MENDS trial (published 2012) required 39.5 hours of staff time with total estimated associated cost of £2540. Clinical trial researchers, funders and sponsors should consider appropriate resourcing and allow reasonable time for preparing IPD ready for subsequent sharing. This process would be most efficient if prospectively built into the standard operational design and conduct of a clinical trial. Further empirical examples exploring the resource requirements in other settings is recommended. SANAD: International Standard Randomised Controlled Trials Registry: ISRCTN38354748 . Registered on 25 April 2003. EU Clinical Trials Register Eudract 2006-004025-28 . Registered on 16 May 2007. International Standard Randomised Controlled Trials Registry: ISRCTN05534585 /MREC 07/MRE08/43. Registered on 26 January 2007.

Error-related negativity varies with the activation of gender stereotypes.

PubMed

Ma, Qingguo; Shu, Liangchao; Wang, Xiaoyi; Dai, Shenyi; Che, Hongmin

2008-09-19

The error-related negativity (ERN) was suggested to reflect the response-performance monitoring process. The purpose of this study is to investigate how the activation of gender stereotypes influences the ERN. Twenty-eight male participants were asked to complete a tool or kitchenware identification task. The prime stimulus is a picture of a male or female face and the target stimulus is either a kitchen utensil or a hand tool. The ERN amplitude on male-kitchenware trials is significantly larger than that on female-kitchenware trials, which reveals the low-level, automatic activation of gender stereotypes. The ERN that was elicited in this task has two sources--operation errors and the conflict between the gender stereotype activation and the non-prejudice beliefs. And the gender stereotype activation may be the key factor leading to this difference of ERN. In other words, the stereotype activation in this experimental paradigm may be indexed by the ERN.

Administrator Evaluation--Planning and Process.

ERIC Educational Resources Information Center

Sweeney, Jim

1981-01-01

Discusses five tasks basic to effective administrator evaluation: development of district philosophy; identification of activities crucial to school success; determination of operational procedures; utilization of forms and records which reflect district philosophy; and examination of the components of the system during a trial period. (JD)

Trial application of reliability technology to emergency diesel generators at the Trojan Nuclear Power Plant

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

Wong, S.M.; Boccio, J.L.; Karimian, S.

1986-01-01

In this paper, a trial application of reliability technology to the emergency diesel generator system at the Trojan Nuclear Power Plant is presented. An approach for formulating a reliability program plan for this system is being developed. The trial application has shown that a reliability program process, using risk- and reliability-based techniques, can be interwoven into current plant operational activities to help in controlling, analyzing, and predicting faults that can challenge safety systems. With the cooperation of the utility, Portland General Electric Co., this reliability program can eventually be implemented at Trojan to track its effectiveness.

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

PubMed

Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

2015-12-15

Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.

Local or General Anesthesia for Open Hernia Repair: A Randomized Trial

PubMed Central

O’Dwyer, Patrick J.; Serpell, Michael G.; Millar, Keith; Paterson, Caron; Young, David; Hair, Alan; Courtney, Carol-Ann; Horgan, Paul; Kumar, Sudhir; Walker, Andrew; Ford, Ian

2003-01-01

Objective To compare patient outcome following repair of a primary groin hernia under local (LA) or general anesthesia (GA) in a randomized clinical trial. Summary Background Data LA hernia repair is thought to be safer for patients, causes less postoperative pain, cost less, and is associated with a more rapid recovery when compared with the same operation performed under GA. Methods All patients presenting to three surgeons during the study period with a primary groin hernia were considered eligible. Outcome parameters measured including tests of vigilance, divided attention, sustained attention, memory, cognitive function, pain, return to normal activity, and costs. Results Two hundred seventy-nine patients were randomized to LA or GA hernia repair; 276 of these had an operation, with 138 participants in each group. At 6, 24, and 72 hours postoperatively there were no differences in vigilance or divided attention between the groups. Similarly, memory, sustained attention, and cognitive function were not impaired in either group. Although physical activity was significantly impaired at 24 hours, this and return to usual social activities were similar in both groups. While patients in the LA group had significantly less pain on moving, at 6 hours they were less likely to recommend the same operation to someone else. GA hernia repair cost 4% more than the same operation under LA. Conclusions There are no major differences in patient recovery after LA or GA hernia repair. Patients should be offered a choice of anesthesia, LA or GA, for repair of their groin hernia. PMID:12677155

Transformation of Cortex-wide Emergent Properties during Motor Learning.

PubMed

Makino, Hiroshi; Ren, Chi; Liu, Haixin; Kim, An Na; Kondapaneni, Neehar; Liu, Xin; Kuzum, Duygu; Komiyama, Takaki

2017-05-17

Learning involves a transformation of brain-wide operation dynamics. However, our understanding of learning-related changes in macroscopic dynamics is limited. Here, we monitored cortex-wide activity of the mouse brain using wide-field calcium imaging while the mouse learned a motor task over weeks. Over learning, the sequential activity across cortical modules became temporally more compressed, and its trial-by-trial variability decreased. Moreover, a new flow of activity emerged during learning, originating from premotor cortex (M2), and M2 became predictive of the activity of many other modules. Inactivation experiments showed that M2 is critical for the post-learning dynamics in the cortex-wide activity. Furthermore, two-photon calcium imaging revealed that M2 ensemble activity also showed earlier activity onset and reduced variability with learning, which was accompanied by changes in the activity-movement relationship. These results reveal newly emergent properties of macroscopic cortical dynamics during motor learning and highlight the importance of M2 in controlling learned movements. Copyright © 2017 Elsevier Inc. All rights reserved.

Handheld Automated Microsurgical Instrumentation for Intraocular Laser Surgery

PubMed Central

Yang, Sungwook; Lobes, Louis A.; Martel, Joseph N.; Riviere, Cameron N.

2016-01-01

Background and Objective Laser photocoagulation is a mainstay or adjuvant treatment for a variety of common retinal diseases. Automated laser photocoagulation during intraocular surgery has not yet been established. The authors introduce an automated laser photocoagulation system for intraocular surgery, based on a novel handheld instrument. The goals of the system are to enhance accuracy and efficiency and improve safety. Materials and Methods Triple-ring patterns are introduced as a typical arrangement for the treatment of proliferative retinopathy and registered to a preoperative fundus image. In total, 32 target locations are specified along the circumferences of three rings having diameters of 1, 2, and 3 mm, with a burn spacing of 600 μm. Given the initial system calibration, the retinal surface is reconstructed using stereo vision, and the targets specified on the preoperative image are registered with the control system. During automated operation, the laser probe attached to the manipulator of the active handheld instrument is deflected as needed via visual servoing in order to correct the error between the aiming beam and a specified target, regardless of any erroneous handle motion by the surgeon. A constant distance of the laser probe from the retinal surface is maintained in order to yield consistent size of burns and ensure safety during operation. Real-time tracking of anatomical features enables compensation for any movement of the eye. A graphical overlay system within operating microscope provides the surgeon with guidance cues for automated operation. Two retinal surgeons performed automated and manual trials in an artificial model of the eye, with each trial repeated three times. For the automated trials, various targeting thresholds (50–200 μm) were used to automatically trigger laser firing. In manual operation, fixed repetition rates were used, with frequencies of 1.0–2.5 Hz. The power of the 532 nm laser was set at 3.0 W with a duration of 20 ms. After completion of each trial, the speed of operation and placement error of burns were measured. The performance of the automated laser photocoagulation was compared with manual operation, using interpolated data for equivalent firing rates from 1.0 to 1.75 Hz. Results In automated trials, average error increased from 45 ± 27 to 60 ± 37 μm as the targeting threshold varied from 50 to 200 μm, while average firing rate significantly increased from 0.69 to 1.71 Hz. The average error in the manual trials increased from 102 ± 67 to 174 ± 98 μm as firing rate increased from 1.0 to 2.5 Hz. Compared to the manual trials, the average error in the automated trials was reduced by 53.0–56.4%, resulting in statistically significant differences (P ≤ 10−20) for all equivalent frequencies (1.0–1.75 Hz). The depth of the laser tip in the automated trials was consistently maintained within 18 ± 2 μm root-mean-square (RMS) of its initial position, whereas it significantly varied in the manual trials, yielding an error of 296 ± 30 μm RMS. At high firing rates in manual trials, such as at 2.5 Hz, laser photocoagulation is marginally attained, yielding failed burns of 30% over the entire pattern, whereas no failed burns are found in automated trials. Relatively regular burn sizes are attained in the automated trials by the depth servoing of the laser tip, while burn sizes in the manual trials vary considerably. Automated avoidance of blood vessels was also successfully demonstrated, utilizing the retina-tracking feature to identify avoidance zones. Conclusion Automated intraocular laser surgery can improve the accuracy of photocoagulation while ensuring safety during operation. This paper provides an initial demonstration of the technique under reasonably realistic laboratory conditions; development of a clinically applicable system requires further work. PMID:26287813

Protocol for a feasibility cluster randomised controlled trial of a peer-led school-based intervention to increase the physical activity of adolescent girls (PLAN-A).

PubMed

Sebire, Simon J; Edwards, Mark J; Campbell, Rona; Jago, Russell; Kipping, Ruth; Banfield, Kathryn; Tomkinson, Keeley; Garfield, Kirsty; Lyons, Ronan A; Simon, Joanne; Blair, Peter S; Hollingworth, William

2016-01-01

Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels. A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer-supporters. Approximately 15 % of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer-supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer-supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully-powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be largely descriptive and focus on recruitment, attendance and data provision rates. The findings will inform the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders (i.e. pupils, parents, teachers and peer-supporter trainers) to identify areas of success and necessary improvements prior to proceeding to a definitive trial. This paper describes the protocol for the PLAN-A feasibility cluster randomised controlled trial which will provide the information necessary to design a fully-powered trial should PLAN-A demonstrate evidence of promise. ISRCTN12543546.

Virtual reality training for surgical trainees in laparoscopic surgery.

PubMed

Nagendran, Myura; Gurusamy, Kurinchi Selvan; Aggarwal, Rajesh; Loizidou, Marilena; Davidson, Brian R

2013-08-27

Standard surgical training has traditionally been one of apprenticeship, where the surgical trainee learns to perform surgery under the supervision of a trained surgeon. This is time-consuming, costly, and of variable effectiveness. Training using a virtual reality simulator is an option to supplement standard training. Virtual reality training improves the technical skills of surgical trainees such as decreased time for suturing and improved accuracy. The clinical impact of virtual reality training is not known. To assess the benefits (increased surgical proficiency and improved patient outcomes) and harms (potentially worse patient outcomes) of supplementary virtual reality training of surgical trainees with limited laparoscopic experience. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded until July 2012. We included all randomised clinical trials comparing virtual reality training versus other forms of training including box-trainer training, no training, or standard laparoscopic training in surgical trainees with little laparoscopic experience. We also planned to include trials comparing different methods of virtual reality training. We included only trials that assessed the outcomes in people undergoing laparoscopic surgery. Two authors independently identified trials and collected data. We analysed the data with both the fixed-effect and the random-effects models using Review Manager 5 analysis. For each outcome we calculated the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals based on intention-to-treat analysis. We included eight trials covering 109 surgical trainees with limited laparoscopic experience. Of the eight trials, six compared virtual reality versus no supplementary training. One trial compared virtual reality training versus box-trainer training and versus no supplementary training, and one trial compared virtual reality training versus box-trainer training. There were no trials that compared different forms of virtual reality training. All the trials were at high risk of bias. Operating time and operative performance were the only outcomes reported in the trials. The remaining outcomes such as mortality, morbidity, quality of life (the primary outcomes of this review) and hospital stay (a secondary outcome) were not reported. Virtual reality training versus no supplementary training: The operating time was significantly shorter in the virtual reality group than in the no supplementary training group (3 trials; 49 participants; MD -11.76 minutes; 95% CI -15.23 to -8.30). Two trials that could not be included in the meta-analysis also showed a reduction in operating time (statistically significant in one trial). The numerical values for operating time were not reported in these two trials. The operative performance was significantly better in the virtual reality group than the no supplementary training group using the fixed-effect model (2 trials; 33 participants; SMD 1.65; 95% CI 0.72 to 2.58). The results became non-significant when the random-effects model was used (2 trials; 33 participants; SMD 2.14; 95% CI -1.29 to 5.57). One trial could not be included in the meta-analysis as it did not report the numerical values. The authors stated that the operative performance of virtual reality group was significantly better than the control group. Virtual reality training versus box-trainer training: The only trial that reported operating time did not report the numerical values. In this trial, the operating time in the virtual reality group was significantly shorter than in the box-trainer group. Of the two trials that reported operative performance, only one trial reported the numerical values. The operative performance was significantly better in the virtual reality group than in the box-trainer group (1 trial; 19 participants; SMD 1.46; 95% CI 0.42 to 2.50). In the other trial that did not report the numerical values, the authors stated that the operative performance in the virtual reality group was significantly better than the box-trainer group. Virtual reality training appears to decrease the operating time and improve the operative performance of surgical trainees with limited laparoscopic experience when compared with no training or with box-trainer training. However, the impact of this decreased operating time and improvement in operative performance on patients and healthcare funders in terms of improved outcomes or decreased costs is not known. Further well-designed trials at low risk of bias and random errors are necessary. Such trials should assess the impact of virtual reality training on clinical outcomes.

Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression.

PubMed

Alonzo, Angelo; Aaronson, Scott; Bikson, Marom; Husain, Mustafa; Lisanby, Sarah; Martin, Donel; McClintock, Shawn M; McDonald, William M; O'Reardon, John; Esmailpoor, Zeinab; Loo, Colleen

2016-11-01

Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. Copyright © 2016 Elsevier Inc. All rights reserved.

The influence of prophylactic antibiotic administration on post-operative morbidity in dental implant surgery. A prospective double blind randomized controlled clinical trial.

PubMed

Nolan, Rory; Kemmoona, Maher; Polyzois, Ioannis; Claffey, Noel

2014-02-01

A prospective double-blind randomised controlled trial was conducted to test the effect of prophylactic antibiotics on post-operative morbidity and osseointegration of dental implants. Fifty-five subjects scheduled for implant surgery were enrolled. The patients were randomly assigned to the antibiotic (test group) and placebo (control group). Twenty-seven patients (test group) received 3 g amoxicillin one hour pre-operatively, and 28 patients (control group) received placebo capsules 1 h pre-operatively. No post-operative antibiotics were prescribed. Pain diaries and interference with daily activities diaries were kept by the patients for 1 week post-operatively. Signs of post-operative morbidity (swelling, bruising, suppuration and wound dehiscence) were recorded by the principal investigators at day 2 and day 7 following the operation. Osseointegration was assessed at 2nd stage surgery or 3-4 months post-operatively. The results of this study suggest that the use of prophylactic pre-operative antibiotics may result in higher dental implant survival rates (100% vs. 82%). Five implant failures, one in each of five patients, were reported in the placebo group and none in the antibiotic group (P = 0.0515). No significant differences were found for most of the signs of post-operative morbidity 2 and 7 days post-operatively. Only bruising at 2 days following the operation appeared to be higher in the placebo group (P = 0.0511). Post-operative pain (P = 0.01) and interference with daily activities (P = 0.01) appeared to be significantly lower for the antibiotic group after 7 days. Those patients with implant failure reported higher pain (based on the VAS scores) after 2 days (P = 0.003) and after 7 days (P = 0.0005), higher pain (based on the amount of analgesics used) after 7 days (P = 0.001) and higher interference with daily activities (based on the VAS scores) after 2 days (P = 0.005). The use of for dental implant surgery may be justified, as it appears to improve implant survival in the short term and also results in less post-operative pain and interference with daily activities. From the results of this study, it appears that prophylactic antibiotics may also be beneficial both in terms of implant survival, especially when the surgical procedure is prolonged due to its difficulty, high number of implants placed or operator's inexperience. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Transanal hemorrhoidal dearterialization with mucopexy versus open hemorrhoidectomy in the treatment of hemorrhoids: a meta-analysis of randomized control trials.

PubMed

Xu, L; Chen, H; Lin, G; Ge, Q; Qi, H; He, X

2016-12-01

The aim of this study was to analyse the outcomes of transanal hemorrhoidal dearterialization with mucopexy (THDm) versus open hemorrhoidectomy (OH) in the management of hemorrhoids. Randomized controlled trials in English were found by searching PubMed, Web of science, EMBASE, and the Cochrane Library database. Trials that compared THDm with OH were identified. Data were extracted independently for each study, and a meta-analysis was performed using fixed and random effects models. Four trials, including 316 patients, met the inclusion criteria. No statistically significant differences were noted in either total complications or postoperative bleeding, incontinence, recurrent prolapse, and urinary retention rate. Operative time was significantly longer for THDm with Doppler guidance than for THDm without Doppler guidance. Patients returned to normal activities faster after THDm than after OH. No statistically significant differences between THDm and OH were noted with regard to recurrence and reoperation rates. Our meta-analysis shows that THDm and OH are equally effective and can be attempted for the management of hemorrhoids. However, for THDm with Doppler guidance, more instruments and a longer operative time are required. Future large-scale, high-quality, multicenter trials with long-term outcomes are needed to prove these results and determine whether Doppler guidance in THD is truly necessary or not.

Controlled multicenter trial of laparoscopic transabdominal preperitoneal hernioplasty vs Shouldice herniorrhaphy. Early results.

PubMed

Tschudi, J; Wagner, M; Klaiber, C; Brugger, J; Frei, E; Krähenbühl, L; Inderbitzi, R; Hüsler, J; Hsu Schmitz, S

1996-08-01

In February 1993 a prospective randomized multicenter trial was initiated to compare laparoscopic transabdominal preperitoneal hernioplasty to Shouldice herniorrhaphy as performed by surgeons of nonspecialized clinics. Until January 1994, 87 patients with 108 hernias took part in the trial (43 Shouldice and 44 laparoscopic repairs). The laparoscopic procedure took significantly longer than did the open operation but caused less pain as measured by pain analogue score and consumption of paracetamol and narcotics. The postoperative complication rate was 26% in the open and 16% in the laparoscopic group. The patients in the laparoscopic group were discharged earlier and their convalescence was shorter than after open hernia repair. There has been one early recurrence in the laparoscopic and two in the open group to date with a mean follow-up of 201 days. Laparoscopic hernia repair causes less pain than the conventional operation and enables the patient to return to full work and usual activities earlier. The recurrence rate will not be known for 5 years.

Laparoscopic-assisted vaginal hysterectomy vs abdominal hysterectomy for benign disease: a meta-analysis of randomized controlled trials.

PubMed

Yi, Yue-xiong; Zhang, Wei; Zhou, Qi; Guo, Wan-ru; Su, Yu

2011-11-01

The objective of this meta-analysis was to assess whether laparoscopic-assisted vaginal hysterectomy achieves better clinical results compared with abdominal hysterectomy. Medline (PubMed), EMBASE, Web of Science, ProQuest, Cochrane Library and China Biological Medicine Database were searched to identify randomized controlled trials that compared laparoscopic-assisted vaginal hysterectomy with abdominal hysterectomy. Twenty-three trials were studied and the analysis was performed using Review Manager Version 5 and R Version 2.11.1. The results showed that laparoscopic-assisted vaginal hysterectomy was associated with a longer operation time, less blood loss, shorter hospital stay, smaller haemoglobin drop, less postoperative pain, quicker return to normal activities and fewer peri-operative complications. Quality of life is likely to be the key outcome to evaluate the approach for hysterectomy, but further research is needed. For suitable patients and surgeons, laparoscopic-assisted vaginal hysterectomy is a better choice than abdominal hysterectomy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Enrichment of acetogenic bacteria in high rate anaerobic reactors under mesophilic and thermophilic conditions.

PubMed

Ryan, P; Forbes, C; McHugh, S; O'Reilly, C; Fleming, G T A; Colleran, E

2010-07-01

The objective of the current study was to expand the knowledge of the role of acetogenic Bacteria in high rate anaerobic digesters. To this end, acetogens were enriched by supplying a variety of acetogenic growth supportive substrates to two laboratory scale high rate upflow anaerobic sludge bed (UASB) reactors operated at 37 degrees C (R1) and 55 degrees C (R2). The reactors were initially fed a glucose/acetate influent. Having achieved high operational performance and granular sludge development and activity, both reactors were changed to homoacetogenic bacterial substrates on day 373 of the trial. The reactors were initially fed with sodium vanillate as a sole substrate. Although % COD removal indicated that the 55 degrees C reactor out performed the 37 degrees C reactor, effluent acetate levels from R2 were generally higher than from R1, reaching values as high as 5023 mg l(-1). Homoacetogenic activity in both reactors was confirmed on day 419 by specific acetogenic activity (SAA) measurement, with higher values obtained for R2 than R1. Sodium formate was introduced as sole substrate to both reactors on day 464. It was found that formate supported acetogenic activity at both temperatures. By the end of the trial, no specific methanogenic activity (SMA) was observed against acetate and propionate indicating that the methane produced was solely by hydrogenotrophic Archaea. Higher SMA and SAA values against H(2)/CO(2) suggested development of a formate utilising acetogenic population growing in syntrophy with hydrogenotrophic methanogens. Throughout the formate trial, the mesophilic reactor performed better overall than the thermophilic reactor. Copyright 2010 Elsevier Ltd. All rights reserved.

Update to a protocol for a feasibility cluster randomised controlled trial of a peer-led school-based intervention to increase the physical activity of adolescent girls (PLAN-A).

PubMed

Sebire, Simon J; Edwards, Mark J; Campbell, Rona; Jago, Russell; Kipping, Ruth; Banfield, Kathryn; Kadir, Bryar; Garfield, Kirsty; Lyons, Ronan A; Blair, Peter S; Hollingworth, William

2016-01-01

Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence, and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels. In addition, this paper describes an update that has been made to the protocol for the PLAN-A feasibility cluster randomised controlled trial. A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer supporters. Approximately 15% of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be largely descriptive and focus on recruitment, attendance and data provision rates. The findings will inform the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders (i.e. pupils, parents, teachers and peer-supporter trainers) to identify areas of success and necessary improvements prior to proceeding to a definitive trial. The study will provide the information necessary to design a fully powered trial should PLAN-A demonstrate evidence of promise. This paper describes an update to the protocol for the PLAN-A feasibility cluster randomised controlled trial related to the data-linkage component. ISRCTN12543546.

Manipulation of motivating operations and use of a script-fading procedure to teach mands for location to children with language delays.

PubMed

Howlett, Melissa A; Sidener, Tina M; Progar, Patrick R; Sidener, David W

2011-01-01

The effects of contriving motivating operations (MOs) and script fading on the acquisition of the mand "Where's [object]?" were evaluated in 2 boys with language delays. During each session, trials were alternated in which high-preference items were present (abolishing operation [AO] trials) or missing (establishing operation [EO] trials) from their typical locations. Both participants learned to mand during EO trials and not to mand during AO trials during training. Generalization of manding was demonstrated across novel instructors, stimuli, and settings and maintained 3 to 4 weeks following the intervention.

Manipulation of Motivating Operations and Use of a Script-Fading Procedure to Teach Mands for Location to Children with Language Delays

ERIC Educational Resources Information Center

Howlett, Melissa A.; Sidener, Tina M.; Progar, Patrick R.; Sidener, David W.

2011-01-01

The effects of contriving motivating operations (MOs) and script fading on the acquisition of the mand "Where's [object]?" were evaluated in 2 boys with language delays. During each session, trials were alternated in which high-preference items were present (abolishing operation [AO] trials) or missing (establishing operation [EO] trials) from…

HUMeral shaft fractures: measuring recovery after operative versus non-operative treatment (HUMMER): a multicenter comparative observational study.

PubMed

Mahabier, Kiran C; Van Lieshout, Esther M M; Bolhuis, Hugo W; Bos, P Koen; Bronkhorst, Maarten Wga; Bruijninckx, Milko M M; De Haan, Jeroen; Deenik, Axel R; Dwars, Boudewijn J; Eversdijk, Martin G; Goslings, J Carel; Haverlag, Robert; Heetveld, Martin J; Kerver, Albert J H; Kolkman, Karel A; Leenhouts, Peter A; Meylaerts, Sven A G; Onstenk, Ron; Poeze, Martijn; Poolman, Rudolf W; Punt, Bas J; Roerdink, W Herbert; Roukema, Gert R; Sintenie, Jan Bernard; Soesman, Nicolaj M R; Tanka, Andras K F; Ten Holder, Edgar J T; Van der Elst, Maarten; Van der Heijden, Frank H W M; Van der Linden, Frits M; Van der Zwaal, Peer; Van Dijk, Jan P; Van Jonbergen, Hans-Peter W; Verleisdonk, Egbert J M M; Vroemen, Jos P A M; Waleboer, Marco; Wittich, Philippe; Zuidema, Wietse P; Polinder, Suzanne; Verhofstad, Michael H J; Den Hartog, Dennis

2014-02-11

Fractures of the humeral shaft are associated with a profound temporary (and in the elderly sometimes even permanent) impairment of independence and quality of life. These fractures can be treated operatively or non-operatively, but the optimal tailored treatment is an unresolved problem. As no high-quality comparative randomized or observational studies are available, a recent Cochrane review concluded there is no evidence of sufficient scientific quality available to inform the decision to operate or not. Since randomized controlled trials for this injury have shown feasibility issues, this study is designed to provide the best achievable evidence to answer this unresolved problem. The primary aim of this study is to evaluate functional recovery after operative versus non-operative treatment in adult patients who sustained a humeral shaft fracture. Secondary aims include the effect of treatment on pain, complications, generic health-related quality of life, time to resumption of activities of daily living and work, and cost-effectiveness. The main hypothesis is that operative treatment will result in faster recovery. The design of the study will be a multicenter prospective observational study of 400 patients who have sustained a humeral shaft fracture, AO type 12A or 12B. Treatment decision (i.e., operative or non-operative) will be left to the discretion of the treating surgeon. Critical elements of treatment will be registered and outcome will be monitored at regular intervals over the subsequent 12 months. The primary outcome measure is the Disabilities of the Arm, Shoulder, and Hand score. Secondary outcome measures are the Constant score, pain level at both sides, range of motion of the elbow and shoulder joint at both sides, radiographic healing, rate of complications and (secondary) interventions, health-related quality of life (Short-Form 36 and EuroQol-5D), time to resumption of ADL/work, and cost-effectiveness. Data will be analyzed using univariate and multivariable analyses (including mixed effects regression analysis). The cost-effectiveness analysis will be performed from a societal perspective. Successful completion of this trial will provide evidence on the effectiveness of operative versus non-operative treatment of patients with a humeral shaft fracture. The trial is registered at the Netherlands Trial Register (NTR3617).

Contribution of clinical trials to gross domestic product in Hungary

PubMed Central

Kaló, Zoltán; Antal, János; Pénzes, Miklós; Pozsgay, Csilla; Szepezdi, Zsuzsanna; Nagyjánosi, László

2014-01-01

Aim To determine the contribution of clinical trials to the gross domestic product (GDP) in Hungary. Methods An anonymous survey of pharmaceutical companies and clinical research organizations (CROs) was conducted to estimate their clinical trial-related employment and revenues. Clinical trial documents at the National Institute of Pharmacy (NIP) were analyzed to estimate trial-related revenues at health care institutions and the value of investigational medical products (IMPs) based on avoided drug costs. Financial benefits were calculated as 2010 US $ purchasing power parity (PPP) values. Results Clinical trials increased the revenue of Hungarian health care providers by US $165.6 million. The value of IMPs was US $67.0 million. Clinical trial operation and management activities generated 900 jobs and US $166.9 million in revenue among CROs and pharmaceutical companies. Conclusions The contribution of clinical trials to the Hungarian GDP in 2010 amounted to 0.2%. Participation in international clinical trials may result in health, financial, and intangible benefits that contribute to the sustainability of health care systems, especially in countries with severe resource constraints. Although a conservative approach was employed to estimate the economic benefits of clinical trials, further research is necessary to improve the generalizability of our findings. PMID:25358877

Aerial ULV application of Dibrom against Aedes aegypti in simulated urban and rural residences

USDA-ARS?s Scientific Manuscript database

Reaching endophilic Aedes aegypti mosquito vectors of dengue located in human residences with aerial ULV pesticide applications is a prominent complication in operational wide area public health mosquito control activities. We conducted separate trials with a military C-130 fixed wing aircraft fitte...

Does Goal Attainment Scaling improve satisfaction regarding performance of activities of younger knee arthroplasty patients? Study protocol of the randomized controlled ACTION trial.

PubMed

Witjes, Suzanne; Hoorntje, Alexander; Kuijer, P Paul F M; Koenraadt, Koen L M; Blankevoort, Leendert; Kerkhoffs, Gino M M J; van Geenen, Rutger C I

2016-03-02

Knee arthroplasty is being increasingly performed, and also more often in a younger patient population (<65 years of age). Up to 20 % of patients remain dissatisfied after knee arthroplasty, despite the apparent technical success of the operation. Recent studies suggest that the fulfilment of patients' expectations plays an important role in achieving satisfaction. Thus, addressing preoperative expectations more explicitly might improve patient satisfaction. The primary aim of the present study is to investigate the effect of a multidisciplinary, goal attained and individualized rehabilitation on satisfaction of activities of younger patients (<65 years) after knee arthroplasty. A single-centre randomized controlled trial will be conducted. In total, 120 patients (<65 years of age) with knee osteoarthritis who will undergo knee arthroplasty, will be randomly allocated to either goal attainment scaling rehabilitation or usual care rehabilitation. Goal attainment scaling rehabilitation includes drafting individually set rehabilitation goals preoperatively and measuring progress of rehabilitation on a six-point scale (-3 to +2). The primary outcome is patient satisfaction concerning activities in daily life, work and leisure time, including sports. Secondary outcome measures include KOOS, OKS, SQUASH and WORQ questionnaires and activity objectively measured with the Activ8® activity monitor. The findings of this study will help to elucidate whether goal attainment scaling is an effective rehabilitation method for achieving higher levels of patient satisfaction, with a focus on activities, in younger patients after knee arthroplasty. This trial is since June 15(th) 2015 registered at the Dutch Trial Register: NTR5251 .

Group-sequential three-arm noninferiority clinical trial designs

PubMed Central

Ochiai, Toshimitsu; Hamasaki, Toshimitsu; Evans, Scott R.; Asakura, Koko; Ohno, Yuko

2016-01-01

We discuss group-sequential three-arm noninferiority clinical trial designs that include active and placebo controls for evaluating both assay sensitivity and noninferiority. We extend two existing approaches, the fixed margin and fraction approaches, into a group-sequential setting with two decision-making frameworks. We investigate the operating characteristics including power, Type I error rate, maximum and expected sample sizes, as design factors vary. In addition, we discuss sample size recalculation and its’ impact on the power and Type I error rate via a simulation study. PMID:26892481

Pre-operative biliary drainage for obstructive jaundice

PubMed Central

Fang, Yuan; Gurusamy, Kurinchi Selvan; Wang, Qin; Davidson, Brian R; Lin, He; Xie, Xiaodong; Wang, Chaohua

2014-01-01

Background Patients with obstructive jaundice have various pathophysiological changes that affect the liver, kidney, heart, and the immune system. There is considerable controversy as to whether temporary relief of biliary obstruction prior to major definitive surgery (pre-operative biliary drainage) is of any benefit to the patient. Objectives To assess the benefits and harms of pre-operative biliary drainage versus no pre-operative biliary drainage (direct surgery) in patients with obstructive jaundice (irrespective of a benign or malignant cause). Search methods We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2012. Selection criteria We included all randomised clinical trials comparing biliary drainage followed by surgery versus direct surgery, performed for obstructive jaundice, irrespective of the sample size, language, and publication status. Data collection and analysis Two authors independently assessed trials for inclusion and extracted data. We calculated the risk ratio (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence intervals (CI) based on the available patient analyses. We assessed the risk of bias (systematic overestimation of benefit or systematic underestimation of harm) with components of the Cochrane risk of bias tool. We assessed the risk of play of chance (random errors) with trial sequential analysis. Main results We included six trials with 520 patients comparing pre-operative biliary drainage (265 patients) versus no pre-operative biliary drainage (255 patients). Four trials used percutaneous transhepatic biliary drainage and two trials used endoscopic sphincterotomy and stenting as the method of pre-operative biliary drainage. The risk of bias was high in all trials. The proportion of patients with malignant obstruction varied between 60% and 100%. There was no significant difference in mortality (40/265, weighted proportion 14.9%) in the pre-operative biliary drainage group versus the direct surgery group (34/255, 13.3%) (RR 1.12; 95% CI 0.73 to 1.71; P = 0.60). The overall serious morbidity was higher in the pre-operative biliary drainage group (60 per 100 patients in the pre-operative biliary drainage group versus 26 per 100 patients in the direct surgery group) (RaR 1.66; 95% CI 1.28 to 2.16; P = 0.0002). The proportion of patients who developed serious morbidity was significantly higher in the pre-operative biliary drainage group (75/102, 73.5%) in the pre-operative biliary drainage group versus the direct surgery group (37/94, 37.4%) (P < 0.001). Quality of life was not reported in any of the trials. There was no significant difference in the length of hospital stay (2 trials, 271 patients; MD 4.87 days; 95% CI −1.28 to 11.02; P = 0.12) between the two groups. Trial sequential analysis showed that for mortality only a small proportion of the required information size had been obtained. There seemed to be no significant differences in the subgroup of trials assessing percutaneous compared to endoscopic drainage. Authors’ conclusions There is currently not sufficient evidence to support or refute routine pre-operative biliary drainage for patients with obstructive jaundice. Pre-operative biliary drainage may increase the rate of serious adverse events. So, the safety of routine pre-operative biliary drainage has not been established. Pre-operative biliary drainage should not be used in patients undergoing surgery for obstructive jaundice outside randomised clinical trials. PMID:22972086

Firefighter Incident Rehabilitation: Interpreting Heart Rate Responses.

PubMed

Smith, Denise L; Haller, Jeannie M; Benedict, Ron; Moore-Merrell, Lori

2016-01-01

The primary objective of this observational study was to document the heart rate (HR) responses of firefighters during incident rehabilitation following firefighting activity in a high-rise building with a simulated fire on the 10th floor. Additionally, the study investigated potential factors, including firefighting workload, ambient temperature, firefighter movement, and individual characteristics, that may have affected HR during recovery. Firefighters (n = 198) were assigned to perform a simulation of fire suppression, search and rescue, or material support during one of six firefighting trials that involved different crew sizes and ascent modes, and were performed in different environmental conditions. After completing the simulated firefighting activity, firefighters reported to a rehabilitation area on the 8th floor. The rehabilitation area was staffed by firefighter/paramedics. HR was monitored continuously during simulated firefighting activity and a 15-minute rehabilitation period. Average HR during rehabilitation (HRmean) was calculated and compared across trials. Simulated firefighting activity was performed in the summer in Virginia, USA, and ambient conditions varied among trials (mean ± SD: 31 ± 4°C; 46 ± 15% relative humidity; 32 ± 4°C heat index). Duration of simulated firefighting activity ranged from 12.0 to 20.3 minutes among trials (mean: 15.4 ± 5.2 minutes). Over all trials, mean peak HR during simulations was 173 ± 18 beats·min(-1). Mean HR over all trials at entry into rehabilitation was 149 ± 24 beats·min(-1). Following 15 minutes of recovery, mean HR over all trials was 126 ± 23 beats·min(-1). Exploratory analyses revealed that higher workload during firefighting (stair trials), higher ambient temperature (≥30°C), greater movement during rehabilitation (≥0.1 g-force), higher age (≥45 years), and higher BMI (≥30.0 kg·m(-2)) were associated with higher HR responses during rehabilitation. During complex emergency operations, emergency medical service personnel will likely encounter considerable variability in HR responses upon initial evaluation and throughout rehabilitation. Following one bout of firefighting activity during a simulated fire scenario, HR decreased but remained elevated well above resting values following 15 minutes of rehabilitation. Based on current fire service recommendations, the majority of firefighters (88%) would not have been released from rehabilitation and eligible for reassignment after a 15-minute rehabilitation period following a brief bout of simulated firefighting activity. medical monitoring, cardiac strain, firefighting.

The Effect of Patella Eversion on Clinical Outcome Measures in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

PubMed

Zan, Pengfei; Wu, Zhong; Yu, Xiao; Fan, Lin; Xu, Tianyang; Li, Guodong

2016-03-01

During total knee arthroplasty (TKA), surgical exposure requires mobilization technique of the patella. With this trial, we intended to investigate the effect of patella eversion on clinical outcome measures in simultaneous bilateral TKA. We prospectively enrolled 44 patients (88 knees) from April 2008 to June 20l4.One knee was operated with patella eversion (group A) and the other with patella lateral retraction (group B) randomly. Follow-up results, including the operation time, complications, and the time of achieving straight leg raise (SLR) and 90° knee flexion, were recorded. The data of range of motion (ROM) and Visual Analogue Scale score were collected separately at 7 days, 3 months, 6 months, and 1 year postoperatively. The time of achieving SLR was 2.7 ± 0.8 days in group A and 2.1 ± 0.7 DAYS in group B, which were significantly different (P = .032). Significant difference was found on active and passive ROM during the follow-up times between groups A and B, except the passive ROM at 6 months postoperatively. No significant difference was found on operation time, complications, patella baja or tilt, time of achieving 90°knee flexion, and Visual Analogue Scale score during the follow-up times. Patellar eversion was adverse to the early knee function recovery after TKA; it would delay the time of achieving SLR and decrease the passive and active ROM. In addition, more carefully and scientifically designed randomized controlled trials are still required to further prove the claim. Copyright © 2016 Elsevier Inc. All rights reserved.

Toward a Choice-Based Judgment Bias Task for Horses.

PubMed

Hintze, Sara; Roth, Emma; Bachmann, Iris; Würbel, Hanno

2017-01-01

Judgment bias tasks for nonhuman animals are promising tools to assess emotional valence as a measure of animal welfare. In view of establishing a valid judgment bias task for horses, the present study aimed to evaluate 2 versions (go/no-go and active choice) of an auditory judgment bias task for horses in terms of acquisition learning and discrimination of ambiguous cues. Five mares and 5 stallions were randomly assigned to the 2 designs and trained for 10 trials per day to acquire different operant responses to a low-frequency tone and a high-frequency tone, respectively. Following acquisition learning, horses were tested on 4 days with 3 ambiguous-tone trials interspersed between the 10 high-tone and low-tone trials. All 5 go/no-go horses but only one active-choice horse successfully learned their task, indicating that it is more difficult to train horses on an active choice task than on a go/no-go task. During testing, however, go/no-go horses did not differentiate between the 3 different ambiguous cues, thereby making the validity of the test results questionable in terms of emotional valence.

Continuous passive motion and physical therapy (CPM) versus physical therapy (PT) versus delayed physical therapy (DPT) after surgical release for elbow contractures; a study protocol for a prospective randomized controlled trial.

PubMed

Viveen, Jetske; Doornberg, Job N; Kodde, Izaak F; Goossens, Pjotr; Koenraadt, Koen L M; The, Bertram; Eygendaal, Denise

2017-11-22

The elbow is prone to stiffness after trauma. To regain functional elbow motion several conservative- and surgical treatment options are available. Conservative treatment includes physical therapy, intra-articular injections with corticosteroids and a static progressive or dynamic splinting program. If conservative treatment fails, an operative release of the posttraumatic stiff elbow is often performed. The best Evidence-Based rehabilitation protocol for patients after an operative release is unknown to date and differs per surgeon, hospital and country. Options include early- or delayed motion supervised by a physical therapist, immediate continuous passive motion (CPM), (night) splinting and a static progressive or dynamic splinting program. The SET-Study (Stiff Elbow Trial) is a single-centre, prospective, randomized controlled trial. The primary objective of this study is to compare the active Range of Motion (ROM) (flexion arc and rotational arc) twelve months after surgery between three groups. The first group will receive in-hospital CPM in combination with early motion Physical Therapy (PT) supervised by a physical therapist, the second group will receive only in-hospital early motion PT supervised by a physical therapist and the third group will receive outpatient supervised PT from postoperative day seven till ten. Secondary outcome measures will be Patient Reported Outcome Measures (PROMs) including the Mayo Elbow Performance Score (MEPS), the Oxford Elbow Score (OES), the quick Disabilities of Arm, Shoulder and Hand (qDASH) score, Visual Analogue pain Scale in rest and activity (VAS), Pain Catastrophizing Scale (PCS), the Short Form (SF)-36, the Centre for Epidemiological Studies Depression Scale Revised (CESD-R) and the Work Rehabilitation Questionnaire (WORQ) for the upper limb. A successful completion of this trial will provide evidence on the best rehabilitation protocol in order to (re)gain optimal motion after surgical release of the stiff elbow. The trial is registered at the Dutch Trial Register: NTR6067 , 31-8-2016.

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia

PubMed Central

2013-01-01

Background As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. Methods We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon’s two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Results Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. Conclusions SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics. PMID:23819695

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.

PubMed

Yap, Christina; Pettitt, Andrew; Billingham, Lucinda

2013-07-03

As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon's two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.

L-Dopa in Parkinsonism and the Influence of Previous Thalamotomy

PubMed Central

Hughes, R. C.; Polgar, J. G.; Weightman, D.; Walton, John N.

1971-01-01

A double-blind cross-over trial over 24 weeks (10 weeks on the active remedy, 4 weeks off treatment, and 10 weeks on placebo) of the effect of L-dopa on idiopathic Parkinsonism (paralysis agitans) has shown no difference in the response obtained in patients who had undergone previous stereotaxic ventrolateral thalamotomy and in those who had not. Of the 34 patients (18 men and 16 women) in the trial 18 had been operated on (nine unilateral, nine bilateral operations) and 16 had not. All patients entering the trial were taking anticholinergic drugs in stable dosage and these were continued throughout. The only factor which seemed to limit the response to treatment was pre-existing hypertension. Of 31 patients who completed the 10-week treatment period, 12 showed marked improvement, 15 moderate improvement, and 4 and mild or negligible change. It seems that previous ventrolateral thalamotomy affords some protection against the development of L-dopa-induced involuntary limb movements on the side contralateral to the operation. As found by others, maximum benefit was seen in bradykinesia and rigidity and related features but a significant reduction in tremor was also noted during treatment. Side effects (nausea, hypotension, and involuntary movements) were common but rarely limited the therapeutic response. PMID:4923653

Research Nurse | Center for Cancer Research

Cancer.gov

We are looking for a Research Nurse (Accrual Site Coordinator) to join our neuro-oncology clinical team to help us provide administrative and coordination support for the Brain Tumor Trials Collaborative (BTTC). Duties include, but are not limited to, monitoring and overseeing activities pertaining to clinical protocols and administrative operations supporting the BTTC, with

Assessment of Chiropractic Treatment for Low Back Pain, Military Readiness and Smoking Cessation in Military Active Duty Personnel

DTIC Science & Technology

reporting period the study: Published primary results manuscript (in print), drafted secondary outcomes manuscripts. ACT 2 is a randomized controlled trial...of response and reaction times in Special Operations Forces at Ft. Campbell, KY. The study is complete and sites are closed. We published the

Optimistic Biases in Observational Learning of Value

ERIC Educational Resources Information Center

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

2011-01-01

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

Infant Operant Conditioning and Its Implications for Early Intervention.

ERIC Educational Resources Information Center

Lancioni, Giullo E.

1980-01-01

In this article infant operant conditioning studies are grouped according to distinct procedures: free operant; discrete trial with one discriminative stimulus; discrete trial with two or more discriminative stimuli; controlled operant with two or more discriminative stimuli; and unrestricted operant with two or more discriminative stimuli.…

Tight intra-operative blood pressure control versus standard care for patients undergoing hip fracture repair - Hip Fracture Intervention Study for Prevention of Hypotension (HIP-HOP) trial: study protocol for a randomised controlled trial.

PubMed

Moppett, Iain Keith; White, Stuart; Griffiths, Richard; Buggy, Donal

2017-07-25

Hypotension during anaesthesia for hip fracture surgery is common. Recent data suggest that there is an association between the lowest intra-operative blood pressure and mortality, even when adjusted for co-morbidities. This is consistent with data derived from the wider surgical population, where magnitude and duration of hypotension are associated with mortality and peri-operative complications. However, there are no trial to data to support more aggressive blood pressure control. We are conducting a three-centre, randomised, double-blinded pilot study in three hospitals in the United Kingdom. The sample size will be 75 patients (25 from each centre). Randomisation will be done using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be aged >70 years, cognitively intact (Abbreviated Mental Test Score 7 or greater), able to give informed consent and admitted directly through the emergency department with a fractured neck of the femur requiring operative repair. Patients randomised to tight blood pressure control or avoidance of intra-operative hypotension will receive active treatment as required to maintain both of the following: systolic arterial blood pressure >80% of baseline pre-operative value and mean arterial pressure >75 mmHg throughout. All participants will receive standard hospital care, including spinal or general anaesthesia, at the discretion of the clinical team. The primary outcome is a composite of the presence or absence of defined cardiovascular, renal and delirium morbidity within 7 days of surgery (myocardial injury, stroke, acute kidney injury, delirium). Secondary endpoints will include the defined individual morbidities, mortality, early mobility and discharge to usual residence. This is a small-scale pilot study investigating the feasibility of a trial of tight intra-operative blood pressure control in a frail elderly patient group with known high morbidity and mortality. Positive findings will provide the basis for a larger-scale study. ISRCTN Registry identifier: ISRCTN89812075 . Registered on 30 August 2016.

[Augmentin in the clinical picture of infectious diseases].

PubMed

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

1992-09-01

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

Less is More in Antidepressant Clinical Trials: A Meta-Analysis of the Effect of Visit Frequency on Treatment Response and Drop-out

PubMed Central

Rutherford, Bret R; Cooper, Timothy M.; Persaud, Amanda; Brown, Patrick J.; Sneed, Joel R.; Roose, Steven P.

2014-01-01

Objective We investigated how the number of follow-up visits affects response rates and drop-out among patients in antidepressant trials for Major Depressive Disorder (MDD). Data Sources Medline, PsycINFO, and PubMed were searched to identify trials contrasting antidepressants to placebo or active comparator in adults with depression. The index terms “depression—drug therapy,” “depressive disorder—drug therapy,” and “antidepressant agents,” in addition to the class and individual generic name of all antidepressants were combined using the ‘or’ operator. Results were limited to 1) English language articles, 2) publication year 1985 or later, 3) age group ≥ 18, and 4) publication types including clinical trials, controlled clinical trials, meta-analysis, multi-center study, randomized controlled trial, or review. Study Selection Included articles reported trials of approved antidepressant medications for MDD in outpatients aged 18–65, were 6–12 weeks in duration, and had response rates specified using a standardized measure. Trials were excluded for enrolling inpatients, pregnant women, psychotic subjects, or those with treatment-resistant depression. These criteria allowed 9,189 articles identified in the literature review to be narrowed to 111 reports. Data extraction Demographic characteristics, the number of study visits planned in each treatment cell, duration of active treatment, attrition rates, and response rates to medication and placebo were entered into a database. Results In a multilevel meta-analysis, active medication vs. placebo (OR 1.96, p < 0.001), active comparator vs. placebo-controlled study design (OR 1.82, p < 0.001), and longer vs. shorter duration (OR 1.87, p < 0.001) were associated with significantly increased odds of treatment response. After controlling for these variables, the number of study visits did not significantly influence response rates (OR 0.97, p = 0.877). The odds of drop-out were significantly decreased for active comparator vs. placebo-controlled trials (OR 0.67, p = 0.002) and longer vs. shorter duration trials (OR 0.54, p = 0.035), while increasing numbers of study visits significantly increased the odds of participant drop-out (OR 2.77, p < 0.001). Conclusion Visit schedules that are much more frequent than are commonly practiced in the community treatment of depression may increase the expense of clinical trials and make them less generalizable to standard clinical treatment. PMID:23945448

A National Cancer Clinical Trials Network: Recommendations from the Institute of Medicine

PubMed Central

Nass, Sharyl J.; Balogh, Erin; Mendelsohn, John

2010-01-01

Oncology has become one of the most active areas of drug discovery, with more than 800 cancer therapeutics in development. This presents an unprecedented opportunity to improve the outcome for patients with cancer, but also requires an effective and efficient clinical trials network to generate the evidence necessary for regulatory approval and optimal integration of new treatments into clinical care. The Clinical Trials Cooperative Group Program supported by the National Cancer Institute has been instrumental in establishing standards of care in oncology over the last 50 years, but it currently faces numerous challenges that threaten its ability to undertake the large-scale, multi-institutional trials that advance patient care. The Institute of Medicine recently appointed a consensus study committee to assess the organization and operation of the Cooperative Group Program and recommend ways to improve the quality of cancer clinical trials conducted by the Groups and others. The committee developed a set of recommendations, summarized here, that aim to improve the speed and efficiency of trials; incorporate innovative science and trial design; improve prioritization, selection, and support of trials; and increase participation by patients and physicians. PMID:21326081

Fortuitous phenomena: on complexity, pragmatic randomised controlled trials, and knowledge for evidence-based practice.

PubMed

Thompson, Carl

2004-01-01

Many of the interventions that nurses develop and implement are in themselves complex and have to operate in situations of irreducible complexity and uncertainty. This article argues that the primary means of generating knowledge for the evidence-based deployment of complex interventions should be the pragmatic randomised controlled trial. Randomised controlled trials represent the only research design to adequately deal with that which we know and (far more importantly) that which we do not. Using the example of practice development as an exemplar for complexity, and drawing on the objections often voiced as a response to calls to make use of randomised controlled trials in nursing and nursing research, the article presents a developmental framework and some methodological solutions to problems often encountered. Randomised controlled trials, whilst undoubtedly methodologically and strategically challenging, offer the most robust basis for developing primary research knowledge on the effects of complex interventions in nursing and their active components.

Achieving TASAR Operational Readiness

NASA Technical Reports Server (NTRS)

Wing, David J.

2015-01-01

NASA has been developing and testing the Traffic Aware Strategic Aircrew Requests (TASAR) concept for aircraft operations featuring a NASA-developed cockpit automation tool, the Traffic Aware Planner (TAP), which computes traffic/hazard-compatible route changes to improve flight efficiency. The TAP technology is anticipated to save fuel and flight time and thereby provide immediate and pervasive benefits to the aircraft operator, as well as improving flight schedule compliance, passenger comfort, and pilot and controller workload. Previous work has indicated the potential for significant benefits for TASAR-equipped aircraft, and a flight trial of the TAP software application in the National Airspace System has demonstrated its technical viability. This paper reviews previous and ongoing activities to prepare TASAR for operational use.

Operating room fire prevention: creating an electrosurgical unit fire safety device.

PubMed

Culp, William C; Kimbrough, Bradly A; Luna, Sarah; Maguddayao, Aris J

2014-08-01

To reduce the incidence of surgical fires. Operating room fires represent a potentially life-threatening hazard and are triggered by the electrosurgical unit (ESU) pencil. Carbon dioxide is a fire suppressant and is a routinely used medical gas. We hypothesize that a shroud of protective carbon dioxide covering the tip of the ESU pencil displaces oxygen, thereby preventing fire ignition. Using 3-dimensional modeling techniques, a polymer sleeve was created and attached to an ESU pencil. This sleeve was connected to a carbon dioxide source and directed the gas through multiple precisely angled ports, generating a cone of fire-suppressive carbon dioxide surrounding the active pencil tip. This device was evaluated in a flammability test chamber containing 21%, 50%, and 100% oxygen with sustained ESU activation. The sleeve was tested with and without carbon dioxide (control) until a fuel was ignited or 30 seconds elapsed. Time to ignition was measured by high-speed videography. Fires were ignited with each control trial (15/15 trials). The control group median ± SD ignition time in 21% oxygen was 3.0 ± 2.4 seconds, in 50% oxygen was 0.1 ± 1.8 seconds, and in 100% oxygen was 0.03 ± 0.1 seconds. No fire was observed when the fire safety device was used in all concentrations of oxygen (0/15 trials; P < 0.0001). The exact 95% confidence interval for absolute risk reduction of fire ignition was 76% to 100%. A sleeve creating a cone of protective carbon dioxide gas enshrouding the sparks from an ESU pencil effectively prevents fire in a high-flammability model. Clinical application of this device may reduce the incidence of operating room fires.

Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

PubMed Central

2009-01-01

Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS) scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis of predictors of the placebo versus treatment response. Whilst this study does not explore neurobiological mechanisms, these observations are consistent with the hypotheses that 'drug' effects and placebo effects are not necessarily additive, and that mutually exclusive mechanisms may be operating in the two arms. The need for more research in the area of mechanisms and mediators of placebo versus active responses is supported. Trial Registration International Clinical Trials Registry ISRCTN98972974. PMID:19549306

Prefrontal cholinergic mechanisms instigating shifts from monitoring for cues to cue-guided performance: Converging electrochemical and fMRI evidence from rats and humans

PubMed Central

Howe, William M.; Berry, Anne S.; Francois, Jennifer; Gilmour, Gary; Carp, Joshua M.; Tricklebank, Mark; Lustig, Cindy; Sarter, Martin

2013-01-01

We previously reported involvement of right prefrontal cholinergic activity in veridical signal detection. Here, we first recorded real-time acetylcholine release in prefrontal cortex during specific trial sequences in rats performing a task requiring signal detection as well as rejection of non-signal events. Cholinergic release events recorded with sub-second resolution (“transients”) were observed only during signal-hit trials, not during signal-miss trials or non-signal events. Moreover, cholinergic transients were not observed for consecutive hits; instead they were limited to signal-hit trials that were preceded by factual or perceived non-signal events (“incongruent hits”). This finding suggests that these transients mediate shifts from a state of perceptual attention, or monitoring for cues, to cue-evoked activation of response rules and the generation of a cue-directed response. Next, to determine the translational significance of the cognitive operations supporting incongruent hits we employed a version of the task previously validated for use in research in humans and BOLD-fMRI. Incongruent hits activated a region in the right rostral prefrontal cortex (BA 10). Furthermore, greater prefrontal activation was correlated with faster response times for incongruent hits. Finally, we measured tissue oxygen in rats, as a proxy for BOLD, and found prefrontal increases in oxygen levels solely during incongruent hits. These cross-species studies link a cholinergic response to a prefrontal BOLD activation and indicate that these interrelated mechanisms mediate the integration of external cues with internal representations to initiate and guide behavior. PMID:23678117

Laparoscopic techniques versus open techniques for inguinal hernia repair.

PubMed

McCormack, K; Scott, N W; Go, P M; Ross, S; Grant, A M

2003-01-01

Inguinal hernia repair is the most frequently performed operation in general surgery. The standard method for inguinal hernia repair had changed little over a hundred years until the introduction of synthetic mesh. This mesh can be placed by either using an open approach or by using a minimal access laparoscopic technique. Although many studies have explored the relative merits and potential risks of laparoscopic surgery for the repair of inguinal hernia, most individual trials have been too small to show clear benefits of one type of surgical repair over another. The objective of this review was to compare minimal access laparoscopic mesh techniques with open techniques. Comparisons of open mesh techniques versus open non-mesh techniques have been considered in a separate Cochrane review. We searched MEDLINE, EMBASE, and The Cochrane Central Controlled Trials Registry for relevant randomised controlled trials. The reference list of identified trials, journal supplements, relevant book chapters and conference proceedings were searched for further relevant trials. Through the EU Hernia Trialists Collaboration (EUHTC) communication took place with authors of identified randomised controlled trials to ask for information on any other recent and ongoing trials known to them. Specialists involved in research on the repair of inguinal hernia were contacted to ask for information about any further completed and ongoing trials. The world wide web was also searched. All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic groin hernia repair with open groin hernia repair were eligible for inclusion. Trials were included irrespective of the language in which they were reported. Individual patient data were obtained, where possible, from the responsible trialist for all eligible studies. All reanalyses were cross-checked by the reviewers and verified by the trialists before inclusion. Where IPD were unavailable additional aggregate data were sought from trialists and published aggregate data checked and verified by the trialists. IPD were available for 25 trials, additional aggregated data for seven and published data only for nine. Where possible, time to event analysis for hernia recurrence and return to usual activities were performed on an intention to treat principle. The main analyses were based on all trials. Sensitivity analyses based on the data source and trial quality were also performed. Pre-defined subgroup analyses based on recurrent hernias, bilateral hernias and femoral hernias were also carried out. 41 published reports of eligible trials were included involving 7161 participants. Sample sizes ranged from 38 to 994, with follow-up from 6 weeks to 36 months. Duration of operation was longer in the laparoscopic groups (WMD 14.81 minutes, 95% CI 13.98 to 15.64; p<0001). Operative complications were uncommon for both methods but more frequent in the laparoscopic group for visceral (Overall 8/2315 versus 1/2599) and vascular (Overall 7/2498 versus 5/2758) injuries. Length of hospital stay did not differ between groups (WMD -0.04 days, 95% CI -0.08 to 0.00; p=0.05, but return to usual activity was earlier for laparoscopic groups (HR 0.56, 95%CI 0.51 to 0.61; p<0.0001 - equivalent to 7 days). The data available showed less persisting pain (Overall 290/2101 versus 459/2399; Peto OR 0.54, 95% CI 0.46 to 0.64; p<0.0001), and less persisting numbness (Overall 102/1419 versus 217/1624; Peto OR 0.38, 95% CI 0.4286 to 0.49; p<0.0001) in the laparoscopic groups. In total, 86 recurrences were reported amongst 3138 allocated laparoscopic repair and 109 amongst 3504 allocated to open repair (Peto OR 0.81, 95% CI 0.61 to 1.08; p = 0.16). The use of mesh during laparoscopic hernia repair is associated with a reduction in the risk of hernia recurrence, significantly so for the transabdominal preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus 47/1119; Peto OR 0.45, 95% CI 0.28 to 0.72; p=0.0009). However, no difference was detected when comparing laparoscopic methods with open mesh methods of hernia repair. The use of mesh during laparoscopic hernia repair is associated with a relative reduction in the risk of hernia recurrence of around 30-50%. However, there is no apparent difference in recurrence between laparoscopic and open mesh methods of hernia repair. The data suggests less persisting pain and numbness following laparoscopic repair. Return to usual activities is faster. However, operation times are longer and there appears to be a higher risk of serious complication rate in respect of visceral (especially bladder) and vascular injuries.

Semantic and Phonological Encoding Times in Adults Who Stutter: Brain Electrophysiological Evidence.

PubMed

Maxfield, Nathan D

2017-10-17

Some psycholinguistic theories of stuttering propose that language production operates along a different time course in adults who stutter (AWS) versus typically fluent adults (TFA). However, behavioral evidence for such a difference has been mixed. Here, the time course of semantic and phonological encoding in picture naming was compared in AWS (n = 16) versus TFA (n = 16) by measuring 2 event-related potential (ERP) components: NoGo N200, an ERP index of response inhibition, and lateralized readiness potential, an ERP index of response preparation. Each trial required a semantic judgment about a picture in addition to a phonemic judgment about the target label of the picture. Judgments were mapped onto a dual-choice (Go-NoGo/left-right) push-button response paradigm. On each trial, ERP activity time-locked to picture onset was recorded at 32 scalp electrodes. NoGo N200 was detected earlier to semantic NoGo trials than to phonemic NoGo trials in both groups, replicating previous evidence that semantic encoding generally precedes phonological encoding in language production. Moreover, N200 onset was earlier to semantic NoGo trials in TFA than in AWS, indicating that semantic information triggering response inhibition became available earlier in TFA versus AWS. In contrast, the time course of N200 activity to phonemic NoGo trials did not differ between groups. Lateralized readiness potential activity was influenced by strategic response preparation and, thus, could not be used to index real-time semantic and phonological encoding. NoGo N200 results point to slowed semantic encoding in AWS versus TFA. Discussion considers possible factors in slowed semantic encoding in AWS and how fluency might be impacted by slowed semantic encoding.

Semantic and Phonological Encoding Times in Adults Who Stutter: Brain Electrophysiological Evidence

PubMed Central

2017-01-01

Purpose Some psycholinguistic theories of stuttering propose that language production operates along a different time course in adults who stutter (AWS) versus typically fluent adults (TFA). However, behavioral evidence for such a difference has been mixed. Here, the time course of semantic and phonological encoding in picture naming was compared in AWS (n = 16) versus TFA (n = 16) by measuring 2 event-related potential (ERP) components: NoGo N200, an ERP index of response inhibition, and lateralized readiness potential, an ERP index of response preparation. Method Each trial required a semantic judgment about a picture in addition to a phonemic judgment about the target label of the picture. Judgments were mapped onto a dual-choice (Go–NoGo/left–right) push-button response paradigm. On each trial, ERP activity time-locked to picture onset was recorded at 32 scalp electrodes. Results NoGo N200 was detected earlier to semantic NoGo trials than to phonemic NoGo trials in both groups, replicating previous evidence that semantic encoding generally precedes phonological encoding in language production. Moreover, N200 onset was earlier to semantic NoGo trials in TFA than in AWS, indicating that semantic information triggering response inhibition became available earlier in TFA versus AWS. In contrast, the time course of N200 activity to phonemic NoGo trials did not differ between groups. Lateralized readiness potential activity was influenced by strategic response preparation and, thus, could not be used to index real-time semantic and phonological encoding. Conclusion NoGo N200 results point to slowed semantic encoding in AWS versus TFA. Discussion considers possible factors in slowed semantic encoding in AWS and how fluency might be impacted by slowed semantic encoding. PMID:28973156

Development of Dry Lubricated Harmonic Drives for Space Applications ('HarmLES')

NASA Astrophysics Data System (ADS)

Jansson, Markus; Koenen, Hans; Viviente, Jose-Luis; Tvaruzka, Adam; Merstallinger, Andreas

2013-09-01

Today, Harmonic Drive® gears are used in several space flight mechanisms as they provide advantages like zero backlash, a high gear stiffness and a high transmission accuracy. In most cases those gears are used in grease lubricated condition, whereas this is always linked to the risk of outgassing and limits significantly the operational temperature.In order to increase the temperature range, trials to apply solid lubricants to Harmonic Drive® gears, as commonly used for e. g. bearings, were performed. Based on these trials it was found that the gears can be operated even at -269°C. Anyhow, although being used in various cryogenic applications, the reachable lifetime is comparably short. Hence the EU - funded project harmLES was started in 2011 in order to increase the accessible lifetime by developing a new Harmonic Drive® gear type. This activity is based on an integrated approach covering gear design, materials and coating.

Smart garments for emergency operators: results of laboratory and field tests.

PubMed

Curone, Davide; Dudnik, Gabriela; Loriga, Giannicola; Magenes, Giovanni; Secco, Emanuele Lindo; Tognetti, Alessandro; Bonfiglio, Annalisa

2008-01-01

The first generation of ProeTEX prototypes has been completed at the end of August 2007. In the following period two main activities have involved the project partners. On one hand new technologies (in terms of sensors and devices) to be integrated in the next releases of prototypes have been developed; on the other hand intensive test sessions on the first prototype (both in laboratory conditions and simulating real operative scenarios) have been carried out. This paper is mainly focused on this second facet. Great efforts have been dedicated to the trials for different reasons: firstly to investigate the appropriateness and efficiency of the system in normal and harsh conditions; secondly to obtain useful indications regarding usability and efficacy by the end-users involved in the project. The results of the trials have been used to define the specifications of the second generation of prototypes, that will be released within the end of 2008.

Multimodality therapy of local regional esophageal cancer.

PubMed

Kelsen, David P

2005-12-01

Recent trials regarding the use of multimodality therapy for patients with cancers of the esophagus and gastroesophageal junction have not conclusively shown benefit. Regimens containing cisplatin and fluorouracil administered preoperatively appear to be tolerable and do not increase operative morbidity or mortality when compared with surgery alone. Yet clinical trials have not clearly shown that such regimens improve outcome as measured by survival. Likewise, trials of postoperative chemoradiation have not reported a significant improvement in median or overall survival. The reasons for the lack of clinical benefit from multimodality therapy are not completely understood, but improvements in systemic therapy will probably be necessary before disease-free or overall survival improves substantially. Some new single agents such as the taxanes (docetaxel or paclitaxel) and the camptothecan analog irinotecan have shown modest activity for palliative therapy.

Enhancing clinical evidence by proactively building quality into clinical trials.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

2016-08-01

Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the different perspectives within and external to an organization (e.g. clinical investigators, research site staff, and trial participants) in improving trial design. Workshop participants also recognized the value of focusing oversight on those aspects of the trial where errors would have a major impact on participant safety and reliability of results. Applying the Clinical Trials Transformation Initiative quality-by-design recommendations and principles should enable organizations to prioritize the most critical determinants of a trial's quality, identify non-essential activities that can be eliminated to streamline trial conduct and oversight, and formulate appropriate plans to define, avoid, mitigate, monitor, and address important errors. © The Author(s) 2016.

The behavioural response of migrating humpback whales to a full seismic airgun array.

PubMed

Dunlop, Rebecca A; Noad, Michael J; McCauley, Robert D; Kniest, Eric; Slade, Robert; Paton, David; Cato, Douglas H

2017-12-20

Despite concerns on the effects of noise from seismic survey airguns on marine organisms, there remains uncertainty as to the biological significance of any response. This study quantifies and interprets the response of migrating humpback whales ( Megaptera novaeangliae ) to a 3130 in 3 (51.3l) commercial airgun array. We compare the behavioural responses to active trials (array operational; n = 34 whale groups), with responses to control trials (source vessel towing the array while silent; n = 33) and baseline studies of normal behaviour in the absence of the vessel ( n = 85). No abnormal behaviours were recorded during the trials. However, in response to the active seismic array and the controls , the whales displayed changes in behaviour. Changes in respiration rate were of a similar magnitude to changes in baseline groups being joined by other animals suggesting any change group energetics was within their behavioural repertoire. However, the reduced progression southwards in response to the active treatments, for some cohorts, was below typical migratory speeds. This response was more likely to occur within 4 km from the array at received levels over 135 dB re 1 µPa 2 s. © 2017 The Author(s).

Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial.

PubMed

Scheltens, Philip; Kamphuis, Patrick J G H; Verhey, Frans R J; Olde Rikkert, Marcel G M; Wurtman, Richard J; Wilkinson, David; Twisk, Jos W R; Kurz, Alexander

2010-01-01

To investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD). A total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale-revised, and the 13-item modified Alzheimer's Disease Assessment Scale-cognitive subscale at week 12. At 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P = .021). Modified Alzheimer's Disease Assessment Scale-cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study-Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated. Supplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials. 2010 The Alzheimer's Association. All rights reserved.

Robotic arm-assisted versus conventional unicompartmental knee arthroplasty: Exploratory secondary analysis of a randomised controlled trial.

PubMed

Blyth, M J G; Anthony, I; Rowe, P; Banger, M S; MacLean, A; Jones, B

2017-11-01

This study reports on a secondary exploratory analysis of the early clinical outcomes of a randomised clinical trial comparing robotic arm-assisted unicompartmental knee arthroplasty (UKA) for medial compartment osteoarthritis of the knee with manual UKA performed using traditional surgical jigs. This follows reporting of the primary outcomes of implant accuracy and gait analysis that showed significant advantages in the robotic arm-assisted group. A total of 139 patients were recruited from a single centre. Patients were randomised to receive either a manual UKA implanted with the aid of traditional surgical jigs, or a UKA implanted with the aid of a tactile guided robotic arm-assisted system. Outcome measures included the American Knee Society Score (AKSS), Oxford Knee Score (OKS), Forgotten Joint Score, Hospital Anxiety Depression Scale, University of California at Los Angeles (UCLA) activity scale, Short Form-12, Pain Catastrophising Scale, somatic disease (Primary Care Evaluation of Mental Disorders Score), Pain visual analogue scale, analgesic use, patient satisfaction, complications relating to surgery, 90-day pain diaries and the requirement for revision surgery. From the first post-operative day through to week 8 post-operatively, the median pain scores for the robotic arm-assisted group were 55.4% lower than those observed in the manual surgery group (p = 0.040).At three months post-operatively, the robotic arm-assisted group had better AKSS (robotic median 164, interquartile range (IQR) 131 to 178, manual median 143, IQR 132 to 166), although no difference was noted with the OKS.At one year post-operatively, the observed differences with the AKSS had narrowed from a median of 21 points to a median of seven points (p = 0.106) (robotic median 171, IQR 153 to 179; manual median 164, IQR 144 to 182). No difference was observed with the OKS, and almost half of each group reached the ceiling limit of the score (OKS > 43). A greater proportion of patients receiving robotic arm-assisted surgery improved their UCLA activity score.Binary logistic regression modelling for dichotomised outcome scores predicted the key factors associated with achieving excellent outcome on the AKSS: a pre-operative activity level > 5 on the UCLA activity score and use of robotic-arm surgery. For the same regression modelling, factors associated with a poor outcome were manual surgery and pre-operative depression. Robotic arm-assisted surgery results in improved early pain scores and early function scores in some patient-reported outcomes measures, but no difference was observed at one year post-operatively. Although improved results favoured the robotic arm-assisted group in active patients (i.e. UCLA ⩾ 5), these do not withstand adjustment for multiple comparisons. Cite this article : M. J. G. Blyth, I. Anthony, P. Rowe, M. S. Banger, A. MacLean, B. Jones. Robotic arm-assisted versus conventional unicompartmental knee arthroplasty: Exploratory secondary analysis of a randomised controlled trial. Bone Joint Res 2017;6:631-639. DOI: 10.1302/2046-3758.611.BJR-2017-0060.R1. © 2017 Blyth et al.

Proof of concept for a new energy-positive wastewater treatment scheme.

PubMed

Remy, C; Boulestreau, M; Lesjean, B

2014-01-01

For improved exploitation of the energy content present in the organic matter of raw sewage, an innovative concept for treatment of municipal wastewater is tested in pilot trials and assessed in energy balance and operational costs. The concept is based on a maximum extraction of organic matter into the sludge via coagulation, flocculation and microsieving (100 μm mesh size) to increase the energy recovery in anaerobic sludge digestion and decrease aeration demand for carbon mineralisation. Pilot trials with real wastewater yield an extraction of 70-80% of total chemical oxygen demand into the sludge while dosing 15-20 mg/L Al and 5-7 mg/L polymer with stable operation of the microsieve and effluent limits below 2-3 mg/L total phosphorus. Anaerobic digestion of the microsieve sludge results in high biogas yields of 600 NL/kg organic dry matter input (oDMin) compared to 430 NL/kg oDMin for mixed sludge from a conventional activated sludge process. The overall energy balance for a 100,000 population equivalent (PE) treatment plant (including biofilter for post-treatment with full nitrification and denitrification with external carbon source) shows that the new concept is an energy-positive treatment process with comparable effluent quality than conventional processes, even when including energy demand for chemicals production. Estimated operating costs for electricity and chemicals are in the same range for conventional activated sludge processes and the new concept.

Electrokinetic remediation of plutonium-contaminated nuclear site wastes: results from a pilot-scale on-site trial.

PubMed

Agnew, Kieran; Cundy, Andrew B; Hopkinson, Laurence; Croudace, Ian W; Warwick, Phillip E; Purdie, Philip

2011-02-28

This paper examines the field-scale application of a novel low-energy electrokinetic technique for the remediation of plutonium-contaminated nuclear site soils, using soil wastes from the Atomic Weapons Establishment (AWE) Aldermaston site, Berkshire, UK as a test medium. Soils and sediments with varying composition, contaminated with Pu through historical site operations, were electrokinetically treated at laboratory-scale with and without various soil pre-conditioning agents. Results from these bench-scale trials were used to inform a larger on-site remediation trial, using an adapted containment pack with battery power supply. 2.4 m(3) (ca. 4t onnes) of Pu-contaminated soil was treated for 60 days at a power consumption of 33 kWh/m(3), and then destructively sampled. Radiochemical data indicate mobilisation of Pu in the treated soil, and migration (probably as a negatively charged Pu-citrate complex) towards the anodic compartment of the treatment cell. Soil in the cathodic zone of the treatment unit was remediated to a level below free-release disposal thresholds (1.7 Bq/g, or <0.4 Bq/g above background activities). The data show the potential of this method as a low-cost, on-site tool for remediation of radioactively contaminated soils and wastes which can be operated remotely on working sites, with minimal disruption to site infrastructure or operations. Copyright © 2010 Elsevier B.V. All rights reserved.

Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis.

PubMed

Tupasi, Thelma; Gupta, Rajesh; Danilovits, Manfred; Cirule, Andra; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Gentry, Leesa M; Geiter, Lawrence J; Wells, Charles D

2016-02-01

New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.

Randomization in clinical trials: stratification or minimization? The HERMES free simulation software.

PubMed

Fron Chabouis, Hélène; Chabouis, Francis; Gillaizeau, Florence; Durieux, Pierre; Chatellier, Gilles; Ruse, N Dorin; Attal, Jean-Pierre

2014-01-01

Operative clinical trials are often small and open-label. Randomization is therefore very important. Stratification and minimization are two randomization options in such trials. The first aim of this study was to compare stratification and minimization in terms of predictability and balance in order to help investigators choose the most appropriate allocation method. Our second aim was to evaluate the influence of various parameters on the performance of these techniques. The created software generated patients according to chosen trial parameters (e.g., number of important prognostic factors, number of operators or centers, etc.) and computed predictability and balance indicators for several stratification and minimization methods over a given number of simulations. Block size and proportion of random allocations could be chosen. A reference trial was chosen (50 patients, 1 prognostic factor, and 2 operators) and eight other trials derived from this reference trial were modeled. Predictability and balance indicators were calculated from 10,000 simulations per trial. Minimization performed better with complex trials (e.g., smaller sample size, increasing number of prognostic factors, and operators); stratification imbalance increased when the number of strata increased. An inverse correlation between imbalance and predictability was observed. A compromise between predictability and imbalance still has to be found by the investigator but our software (HERMES) gives concrete reasons for choosing between stratification and minimization; it can be downloaded free of charge. This software will help investigators choose the appropriate randomization method in future two-arm trials.

Early versus delayed post-operative bathing or showering to prevent wound complications.

PubMed

Toon, Clare D; Sinha, Sidhartha; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2015-07-23

Many people undergo surgical operations during their life-time, which result in surgical wounds. After an operation the incision is closed using stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of the surgical procedure and before the patient leaves the operating theatre, the surgeon covers the closed surgical wound using gauze and adhesive tape or an adhesive tape containing a pad (a wound dressing) that covers the surgical wound. There is currently no guidance about when the wound can be made wet by post-operative bathing or showering. Early bathing may encourage early mobilisation of the patient, which is good after most types of operation. Avoiding post-operative bathing or showering for two to three days may result in accumulation of sweat and dirt on the body. Conversely, early washing of the surgical wound may have an adverse effect on healing, for example by irritating or macerating the wound, and disturbing the healing environment. To compare the benefits (such as potential improvements to quality of life) and harms (potentially increased wound-related morbidity) of early post-operative bathing or showering (i.e. within 48 hours after surgery, the period during which epithelialisation of the wound occurs) compared with delayed post-operative bathing or showering (i.e. no bathing or showering for over 48 hours after surgery) in patients with closed surgical wounds. We searched The Cochrane Wounds Group Specialised Register (30th June 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP). We considered all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of their wounds, irrespective of the location of the wound and whether or not the wound was dressed. We excluded trials if they included patients with contaminated, dirty or infected wounds and those that included open wounds. We also excluded quasi-randomised trials, cohort studies and case-control studies. We extracted data on the characteristics of the patients included in the trials, risk of bias in the trials and outcomes from each trial. For binary outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables we planned to calculate the mean difference (MD), or standardised mean difference (SMD) with 95% CI. For count data outcomes, we planned to calculate the rate ratio (RaR) with 95% CI. We used RevMan 5 software for performing these calculations. Only one trial was identified for inclusion in this review. This trial was at a high risk of bias. This trial included 857 patients undergoing minor skin excision surgery in the primary care setting. The wounds were sutured after the excision. Patients were randomised to early post-operative bathing (dressing to be removed after 12 hours and normal bathing resumed) (n = 415) or delayed post-operative bathing (dressing to be retained for at least 48 hours before removal and resumption of normal bathing) (n = 442). The only outcome of interest reported in this trial was surgical site infection (SSI). There was no statistically significant difference in the proportion of patients who developed SSIs between the two groups (857 patients; RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients who developed SSIs were 8.5% in the early bathing group and 8.8% in the delayed bathing group. There is currently no conclusive evidence available from randomised trials regarding the benefits or harms of early versus delayed post-operative showering or bathing for the prevention of wound complications, as the confidence intervals around the point estimate are wide, and, therefore, a clinically significant increase or decrease in SSI by early post-operative bathing cannot be ruled out. We recommend running further randomised controlled trials to compare early versus delayed post-operative showering or bathing.

Early versus delayed post-operative bathing or showering to prevent wound complications.

PubMed

Toon, Clare D; Sinha, Sidhartha; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2013-10-12

Many people undergo surgical operations during their life-time, which result in surgical wounds. After an operation the incision is closed using stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of the surgical procedure and before the patient leaves the operating theatre, the surgeon covers the closed surgical wound using gauze and adhesive tape or an adhesive tape containing a pad (a wound dressing) that covers the surgical wound. There is currently no guidance about when the wound can be made wet by post-operative bathing or showering. Early bathing may encourage early mobilisation of the patient, which is good after most types of operation. Avoiding post-operative bathing or showering for two to three days may result in accumulation of sweat and dirt on the body. Conversely, early washing of the surgical wound may have an adverse effect on healing, for example by irritating or macerating the wound, and disturbing the healing environment. To compare the benefits (such as potential improvements to quality of life) and harms (potentially increased wound-related morbidity) of early post-operative bathing or showering (i.e. within 48 hours after surgery, the period during which epithelialisation of the wound occurs) compared with delayed post-operative bathing or showering (i.e. no bathing or showering for over 48 hours after surgery) in patients with closed surgical wounds. We searched The Cochrane Wounds Group Specialised Register;The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP). We considered all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of their wounds, irrespective of the location of the wound and whether or not the wound was dressed. We excluded trials if they included patients with contaminated, dirty or infected wounds and those that included open wounds. We also excluded quasi-randomised trials, cohort studies and case-control studies. We extracted data on the characteristics of the patients included in the trials, risk of bias in the trials and outcomes from each trial. For binary outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI). For continuous variables we planned to calculate the mean difference (MD), or standardised mean difference (SMD) with 95% CI. For count data outcomes, we planned to calculate the rate ratio (RaR) with 95% CI. We used RevMan 5 software for performing these calculations. Only one trial was identified for inclusion in this review. This trial was at a high risk of bias. This trial included 857 patients undergoing minor skin excision surgery in the primary care setting. The wounds were sutured after the excision. Patients were randomised to early post-operative bathing (dressing to be removed after 12 hours and normal bathing resumed) (n = 415) or delayed post-operative bathing (dressing to be retained for at least 48 hours before removal and resumption of normal bathing) (n = 442). The only outcome of interest reported in this trial was surgical site infection (SSI). There was no statistically significant difference in the proportion of patients who developed SSIs between the two groups (857 patients; RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients who developed SSIs were 8.5% in the early bathing group and 8.8% in the delayed bathing group. There is currently no conclusive evidence available from randomised trials regarding the benefits or harms of early versus delayed post-operative showering or bathing for the prevention of wound complications, as the confidence intervals around the point estimate are wide, and, therefore, a clinically significant increase or decrease in SSI by early post-operative bathing cannot be ruled out. We recommend running further randomised controlled trials to compare early versus delayed post-operative showering or bathing.

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.

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Voting for image scoring and assessment (VISA)--theory and application of a 2 + 1 reader algorithm to improve accuracy of imaging endpoints in clinical trials.

PubMed

Gottlieb, Klaus; Hussain, Fez

2015-02-19

Independent central reading or off-site reading of imaging endpoints is increasingly used in clinical trials. Clinician-reported outcomes, such as endoscopic disease activity scores, have been shown to be subject to bias and random error. Central reading attempts to limit bias and improve accuracy of the assessment, two factors that are critical to trial success. Whether one central reader is sufficient and how to best integrate the input of more than one central reader into one output measure, is currently not known.In this concept paper we develop the theoretical foundations of a reading algorithm that can achieve both objectives without jeopardizing operational efficiency We examine the role of expert versus competent reader, frame scoring of imaging as a classification task, and propose a voting algorithm (VISA: Voting for Image Scoring and Assessment) as the most appropriate solution which could also be used to operationally define imaging gold standards. We propose two image readers plus an optional third reader in cases of disagreement (2 + 1) for ordinary scoring tasks. We argue that it is critical in trials with endoscopically determined endpoints to include the score determined by the site reader, at least in endoscopy clinical trials. Juries with more than 3 readers could define a reference standard that would allow a transition from measuring reader agreement to measuring reader accuracy. We support VISA by applying concepts from engineering (triple-modular redundancy) and voting theory (Condorcet's jury theorem) and illustrate our points with examples from inflammatory bowel disease trials, specifically, the endoscopy component of the Mayo Clinic Score of ulcerative colitis disease activity. Detailed flow-diagrams (pseudo-code) are provided that can inform program design.The VISA "2 + 1" reading algorithm, based on voting, can translate individual reader scores into a final score in a fashion that is both mathematically sound (by avoiding averaging of ordinal data) and in a manner that is consistent with the scoring task at hand (based on decisions about the presence or absence of features, a subjective classification task). While the VISA 2 + 1 algorithm is currently being used in clinical trials, empirical data of its performance have not yet been reported.

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

PubMed

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

2014-04-01

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

The effectiveness of non-surgical interventions in the treatment of Charcot foot.

PubMed

Smith, Caroline; Kumar, Saravana; Causby, Ryan

2007-12-01

Background  Charcot neuropathic osteoarthropathy is commonly known as 'Charcot foot'. It is a serious foot complication of diabetes mellitus that can frequently lead to foot ulceration, gangrene, hospital admission and foot amputation. A multidisciplinary approach to the management of Charcot foot is taken involving medical and allied health professionals. The management approach may also differ between different countries. To date, there is no systematic review of the literature undertaken to identify the clinical effectiveness of non-operative interventions in the treatment of acute Charcot foot. Objective  The objective of this review was to identify the effectiveness of non-surgical interventions with reducing lesions, ulceration, the rate of surgical intervention, reducing hospital admissions and improve the quality of life of subjects with Charcot foot. Search strategy  A comprehensive search strategy was undertaken on databases available from University of South Australia from their inception to November 2006. Selection criteria  Randomised controlled trials or clinical controlled trials were primarily sought. Critical appraisal of study quality and data extraction was undertaken using Joanna Briggs Institute instruments. Review Manager software was used to calculate comparative statistics. Results  This review identified 11 trials and five trials were included in the review. Three trials involved the use of bisphosphonate, a pharmacological agent. Two experimental treatments were also included, evaluating palliative radiology and magnetic fields. No trials were found using immobilisation and off-loading interventions for acute Charcot foot. The overall methodological quality score of the five studies was moderate. Owing to heterogeneous data, meta-analysis could not be performed. The trials did not report on reducing lesions, ulceration, rate of surgical intervention, hospital admissions and the quality of life of subjects with Charcot foot. The trials evaluating bisphosphonates reported greater reduction in foot temperature and disease activity for intervention subjects compared with controls. Another outcome of this review indicated additional beneficial effects of bisphosphonates in reducing pain and discomfort. The trial evaluating palliative radiotherapy found no difference between groups on any outcome. A significant reduction in the amount of deformity and reduced healing time to consolidation was found after treatment in the group receiving magnetic therapy treatment. Discussion  There is a lack of clinical trials evaluating the effectiveness of non-operative interventions for the management of Charcot foot (immobilisation, removable cast walkers, advice/dispensing of footwear and prescribing of orthotics). Bisphosphonates may be useful adjuncts to standard management of Charcot foot by improved healing demonstrated by a reduction in disease activity indicated by skin temperature and bone destruction. Magnetic therapy may reduce deformity, joint destruction and improve mobility. Conclusion  There is a lack of evidence supporting the use of pharmacological or non-surgical interventions with reducing lesions, ulceration, rate of surgical intervention, hospital admissions and improving the quality of life of subjects with Charcot foot. Bisphosphonates may improve the healing of Charcot foot by reducing skin temperature and disease activity of Charcot foot, when applied in addition to standard interventions to control the position and shape of the foot.

Characteristics associated with willingness to participate in a randomized controlled behavioral clinical trial using home-based personal computers and a webcam.

PubMed

Dodge, Hiroko H; Katsumata, Yuriko; Zhu, Jian; Mattek, Nora; Bowman, Molly; Gregor, Mattie; Wild, Katherine; Kaye, Jeffrey A

2014-12-23

Trials aimed at preventing cognitive decline through cognitive stimulation among those with normal cognition or mild cognitive impairment are of significant importance in delaying the onset of dementia and reducing dementia prevalence. One challenge in these prevention trials is sample recruitment bias. Those willing to volunteer for these trials could be socially active, in relatively good health, and have high educational levels and cognitive function. These participants' characteristics could reduce the generalizability of study results and, more importantly, mask trial effects. We developed a randomized controlled trial to examine whether conversation-based cognitive stimulation delivered through personal computers, a webcam and the internet would have a positive effect on cognitive function among older adults with normal cognition or mild cognitive impairment. To examine the selectivity of samples, we conducted a mass mail-in survey distribution among community-dwelling older adults, assessing factors associated with a willingness to participate in the trial. Two thousand mail-in surveys were distributed to retirement communities in order to collect data on demographics, the nature and frequency of social activities, personal computer use and additional health-related variables, and interest in the prevention study. We also asked for their contact information if they were interested in being contacted as potential participants in the trial. Of 1,102 surveys returned (55.1% response rate), 983 surveys had complete data for all the variables of interest. Among them, 309 showed interest in the study and provided their contact information (operationally defined as the committed with interest group), 74 provided contact information without interest in the study (committed without interest group), 66 showed interest, but provided no contact information (interest only group), and 534 showed no interest and provided no contact information (no interest group). Compared with the no interest group, the committed with interest group were more likely to be personal computer users (odds ratio (OR) = 2.78), physically active (OR = 1.03) and had higher levels of loneliness (OR = 1.16). Increasing potential participants' familiarity with a personal computer and the internet before trial recruitment could increase participation rates and improve the generalizability of future studies of this type. The trial was registered on 29 March 2012 at ClinicalTirals.gov (ID number NCT01571427).

A Randomized Prospective Trial Comparing Paravertebral Block and General Anesthesia for Operative Treatment of Breast Cancer

DTIC Science & Technology

2001-10-01

block the anesthetic of choice for operative treatment of breast cancer. To test this hypothesis we proposed a prospective randomized clinical trial ...coordinators. Months 4-6. Status: Complete The study’s existing part-time Clinical Trial Coordinator, Mr. John Arbo, was enlisted full-time in June...of full-time Clinical Trial Coordinator for Mount Sinai. ■ Poster presentation by Mount Sinai staff of study goals and methods at a Department of

The where and how of attention-based rehearsal in spatial working memory.

PubMed

Postle, B R; Awh, E; Jonides, J; Smith, E E; D'Esposito, M

2004-07-01

Rehearsal in human spatial working memory is accomplished, in part, via covert shifts of spatial selective attention to memorized locations ("attention-based rehearsal"). We addressed two outstanding questions about attention-based rehearsal: the topography of the attention-based rehearsal effect, and the mechanism by which it operates. Using event-related fMRI and a procedure that randomized the presentation of trials with delay epochs that were either filled with a flickering checkerboard or unfilled, we localized the effect to extrastriate areas 18 and 19, and confirmed its absence in striate cortex. Delay-epoch activity in these extrastriate regions, as well as in superior parietal lobule and intraparietal sulcus, was also lateralized on unfilled trials, suggesting that attention-based rehearsal produces a baseline shift in areas representing the to-be-remembered location in space. No frontal regions (including frontal eye fields) demonstrated lateralized activity consistent with a role in attention-based rehearsal.

Beyond the fence line: corporate social responsibility.

PubMed

Harrison, Myron

2004-02-01

The ability to demonstrate acceptable performance against the expectations of a CSR movement is part of the corporate license to operate in many locations. Because health and medical programs are core elements of these activities, numerous opportunities exist for physicians to contribute to health and prosperity in underdeveloped locations. Individuals who are involved in designing and administrating these activities need to maintain critical objectivity about the actual consequences and maintain a close dialog with the intended beneficiaries. The value of the CSR agenda is beginning a long empirical trial.

Traumeel S® for pain relief following hallux valgus surgery: a randomized controlled trial

PubMed Central

2010-01-01

Background In spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain. Method We performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery. Results Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04). Conclusions Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance. Trial Registration This study was registered at ClinicalTrials.gov. # NCT00279513 PMID:20380750

Operative versus non-operative treatment for closed, displaced, intra-articular fractures of the calcaneus: randomised controlled trial.

PubMed

Griffin, Damian; Parsons, Nick; Shaw, Ewart; Kulikov, Yuri; Hutchinson, Charles; Thorogood, Margaret; Lamb, Sarah E

2014-07-24

To investigate whether surgery by open reduction and internal fixation provides benefit compared with non-operative treatment for displaced, intra-articular calcaneal fractures. Pragmatic, multicentre, two arm, parallel group, assessor blinded randomised controlled trial (UK Heel Fracture Trial). 22 tertiary referral hospitals, United Kingdom. 151 patients with acute displaced intra-articular calcaneal fractures randomly allocated to operative (n=73) or non-operative (n=78) treatment. The primary outcome measure was patient reported Kerr-Atkins score for pain and function (scale 0-100, 100 being the best possible score) at two years after injury. Secondary outcomes were complications; hindfoot pain and function (American Orthopaedic Foot and Ankle Society score); general health (SF-36); quality of life (EQ-5D); clinical examination; walking speed; and gait symmetry. Analysis was by intention to treat. 95% follow-up was achieved for the primary outcome (69 in operative group and 74 in non-operative group), and a complete set of secondary outcomes were available for 75% of participants. There was no significant difference in the primary outcome (mean Kerr-Atkins score 69.8 in operative group v 65.7 in non-operative group; adjusted 95% confidence interval of difference -7.1 to 7.0) or in any of the secondary outcomes between treatment groups. Complications and reoperations were more common in those who received operative care (estimated odds ratio 7.5, 95% confidence interval 2.0 to 41.8). Operative treatment compared with non-operative care showed no symptomatic or functional advantage after two years in patients with typical displaced intra-articular fractures of the calcaneus, and the risk of complications was higher after surgery. Based on these findings, operative treatment by open reduction and internal fixation is not recommended for these fractures.Trial registration Current Controlled Trials ISRCTN37188541. © Griffin et al 2014.

Single-incision versus conventional three-port laparoscopic appendectomy: A meta-analysis of randomized controlled trials.

PubMed

Chen, Jiang-Ming; Geng, Wei; Xie, Sheng-Xue; Liu, Fu-Bao; Zhao, Yi-Jun; Yu, Li-Quan; Geng, Xiao-Ping

2015-01-01

The aim of this article was to compare the advantages and disadvantages of single-incision laparoscopic appendectomy (SILA) and conventional three-port laparoscopic appendectomy (CTLA). A meta-analysis was performed by analyzing all randomized controlled trials (RCTs) published in English that compared SILA and CTLA for appendicitis in adults and children. These studies compared these two methods from different angles including outcomes of interest, patient characteristics, operative time, pain visual analogue scales scores (VAS scores), length of hospital stay, time to return to full activity, resumption of diet, postoperative complications and cosmetic results The risk ratios (RR) and mean difference (MD) with 95% confidence intervals (CIs) were employed to assess the outcome. Seven recent RCTs encompassing 1170 patients (586 SILA and 584 CTLA cases) were included in this meta-analysis. The pooled results demonstrated that conversion rate, drain inserted, reoperation, length of hospital stay, resumption of normal diet and postoperative complications were statistically comparable between the two groups. The postoperative abdominal pain within 24 h was -0.57 in favor of the SILA technique (p = 0.05). Compared with CTLA, SILA showed a better cosmetic satisfaction score (SMD, 0.58; 95% CI, 0.32-0.83; p < 0.0001) and shorter time to recover normal activity (WMD, -0.69; 95% CI, -1.11-0.26; p = 0.001). However, SILA has a longer operative time (WMD, 5.38; 95% CI, 2.94-7.83; p < 0.0001). In selected patients, SILA was confirmed to be as safe and effective as CTLA. Despite the longer operative time, SILA has higher cosmetic satisfaction and shorter recovery time to normal activity. Due to the limitations of the available data, further research is needed.

Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial.

PubMed

Amanullah, Muhammad M; Hamid, Mohammad; Hanif, Hashim M; Muzaffar, Marium; Siddiqui, Maria T; Adhi, Fatima; Ahmad, Khabir; Khan, Shahjahan; Hasan, Zahra

2016-03-01

Cardiopulmonary bypass is associated with systemic inflammatory response. Steroids suppress this response, although the therapeutic evidence remains controversial. We hypothesised that intravenous steroids in children undergoing open-heart surgery would decrease inflammation leading to better early post-operative outcomes. We conducted a randomised controlled trial to evaluate the trends in the levels of immunomodulators and their effects on clinical parameters. To assess the effects of intravenous steroids on early post-operative inflammatory markers and clinical parameters in children undergoing open-heart surgery. A randomised controlled trial involving 152 patients, from one month up to 18 years of age, who underwent open-heart surgery for congenital heart disease from April 2010-2012 was carried out. Patients were randomised and administered either three scheduled intravenous pulse doses of dexamethasone (1 mg/kg) or placebo. Blood samples were drawn at four time intervals and serum levels of inflammatory cytokines - Interleukin-6, 8, 10, 18, and tumour necrosis factor-alpha - were measured. Clinical parameters were also assessed. Blood cytokine levels were compared between the dexamethasone (n=65) and placebo (n=64) groups. Interleukin-6 levels were lower at 6 and 24 hours post-operatively (p<0.001), and Interleukin-10 levels were higher 6 hours post-operatively (p<0.001) in the steroid group. Interleukin-8, 18, and tumour necrosis factor-alpha levels did not differ between the groups at any time intervals. The clinical parameters were similar in both the groups. Dexamethasone caused quantitative suppression of Interleukin-6 and increased Interleukin-10 activation, contributing to reduced immunopathology, but it did not translate into clinical benefit in the short term.

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

PubMed

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

2014-07-20

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

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.

[Standard operating procedures in ethic committees].

PubMed

Czarkowski, Marek

2006-02-01

Polish ethic committees should have to work together in order to maintain and develop high quality standards in the protection of human subjects. Exchanging knowledge, know-how and information polish ethic committees should have to implement standard operating procedures. Procedures should improve quality and proficiency of all types of ethic committee's activities. Standard operating procedures should cover as important problems as conflict of interest, trial's insurance or elections of ethic committees. The opinions of experts who have been reviewing medical research projects for several years may prove to be especially valuable in this setting. Governmental initiatives and creation of forum for polish ethic committees are essential in the effective standardisation, coordination and implementation of procedures in regional ethic committees. These projects need support via public funding from our authorities.

Implementation of the SMART MOVE intervention in primary care: a qualitative study using normalisation process theory.

PubMed

Glynn, Liam G; Glynn, Fergus; Casey, Monica; Wilkinson, Louise Gaffney; Hayes, Patrick S; Heaney, David; Murphy, Andrew W M

2018-05-02

Problematic translational gaps continue to exist between demonstrating the positive impact of healthcare interventions in research settings and their implementation into routine daily practice. The aim of this qualitative evaluation of the SMART MOVE trial was to conduct a theoretically informed analysis, using normalisation process theory, of the potential barriers and levers to the implementation of a mhealth intervention to promote physical activity in primary care. The study took place in the West of Ireland with recruitment in the community from the Clare Primary Care Network. SMART MOVE trial participants and the staff from four primary care centres were invited to take part and all agreed to do so. A qualitative methodology with a combination of focus groups (general practitioners, practice nurses and non-clinical staff from four separate primary care centres, n = 14) and individual semi-structured interviews (intervention and control SMART MOVE trial participants, n = 4) with purposeful sampling utilising the principles of Framework Analysis was utilised. The Normalisation Process Theory was used to develop the topic guide for the interviews and also informed the data analysis process. Four themes emerged from the analysis: personal and professional exercise strategies; roles and responsibilities to support active engagement; utilisation challenges; and evaluation, adoption and adherence. It was evident that introducing a new healthcare intervention demands a comprehensive evaluation of the intervention itself and also the environment in which it is to operate. Despite certain obstacles, the opportunity exists for the successful implementation of a novel healthcare intervention that addresses a hitherto unresolved healthcare need, provided that the intervention has strong usability attributes for both disseminators and target users and coheres strongly with the core objectives and culture of the health care environment in which it is to operate. We carried out a theoretical analysis of stakeholder informed barriers and levers to the implementation of a novel exercise promotion tool in the Irish primary care setting. We believe that this process amplifies the implementation potential of such an intervention in primary care. The SMART MOVE trial is registered at Current Controlled Trials (ISRCTN99944116; Date of registration: 1st August 2012).

Nonoperative versus operative treatment for thoracolumbar burst fractures without neurologic deficit: a meta-analysis.

PubMed

Gnanenthiran, Sonali R; Adie, Sam; Harris, Ian A

2012-02-01

Decision-making regarding nonoperative versus operative treatment of patients with thoracolumbar burst fractures in the absence of neurologic deficits is controversial. Lack of evidence-based practice may result in patients being treated inappropriately and being exposed to unnecessary adverse consequences. Using meta-analysis, we therefore compared pain (VAS) and function (Roland Morris Disability Questionnaire) in patients with thoracolumbar burst fractures without neurologic deficit treated nonoperatively and operatively. Secondary outcomes included return to work, radiographic progression of kyphosis, radiographic progression of spinal canal stenosis, complications, cost, and length of hospitalization. We searched MEDLINE, EMBASE(®), and the Cochrane Central Register of Controlled Trials for 'thoracic fractures', 'lumbar fractures', 'non-operative', 'operative' and 'controlled clinical trials'. We established five criteria for inclusion. Data extraction and quality assessment were in accordance with Cochrane Collaboration guidelines. The main analyses were performed on individual patient data from randomized controlled trials. Sensitivity analyses were performed on VAS pain, Roland Morris Disability Questionnaire score, kyphosis, and return to work, including data from nonrandomized controlled trials and using fixed effects meta-analysis. We identified four trials, including two randomized controlled trials consisting of 79 patients (41 with operative treatment and 38 with nonoperative treatment). The mean followups ranged from 24 to 118 months. We found no between-group differences in baseline pain, kyphosis, and Roland Morris Disability Questionnaire scores. At last followup, there were no between-group differences in pain, Roland Morris Disability Questionnaire scores, and return to work rates. We found an improvement in kyphosis ranging from means of 12.8º to 11º in the operative group, but surgery was associated with higher complication rates and costs. Operative management of thoracolumbar burst fractures without neurologic deficit may improve residual kyphosis, but does not appear to improve pain or function at an average of 4 years after injury and is associated with higher complication rates and costs. Level II, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence.

The effect of night extension orthoses following surgical release of Dupuytren contracture: a single-center, randomized, controlled trial.

PubMed

Collis, Julie; Collocott, Shirley; Hing, Wayne; Kelly, Edel

2013-07-01

To clarify the efficacy and detrimental effects of orthoses used to maintain finger extension following surgical release of Dupuytren contracture. We conducted a single-center, randomized, controlled trial to investigate the effect of night extension orthoses on finger range of motion and hand function for 3 months following surgical release of Dupuytren contracture. We also wanted to determine how well finger extension was maintained in the total sample. We randomized 56 patients to receive a night extension orthosis plus hand therapy (n = 26) or hand therapy alone (n = 30). The primary outcome was total active extension of the operated fingers (°). Secondary outcomes were total active flexion of the operated fingers (°), active distal palmar crease (cm), grip strength (kg), and self-reported hand function using the Disabilities of the Arm, Shoulder, and Hand questionnaire (0-100 scale). There were no statistically significant differences between the no-orthosis and orthosis groups for total active extension or for any of the secondary outcomes. Between the first postoperative measure and 3 months after surgery, 62% of little fingers had maintained or improved total active extension. The use of a night extension orthosis in combination with standard hand therapy has no greater effect on maintaining finger extension than hand therapy alone in the 3 months following surgical release of Dupuytren contracture. Our results indicate that the practice of providing every patient with a night extension orthosis following surgical release of Dupuytren contracture may not be justified except for cases in which extension loss occurs after surgery. Our results also challenge clinicians to research ways of maintaining finger extension in a greater number of patients. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

The effectiveness and cost-evaluation of manual therapy and physical therapy in patients with sub-acute and chronic non specific neck pain. Rationale and design of a Randomized Controlled Trial (RCT)

PubMed Central

2010-01-01

Background Manual Therapy applied to patients with non specific neck pain has been investigated several times. In the Netherlands, manual therapy as applied according to the Utrecht School of Manual Therapy (MTU) has not been the subject of a randomized controlled trial. MTU differs in diagnoses and treatment from other forms of manual therapy. Methods/Design This is a single blind randomized controlled trial in patients with sub-acute and chronic non specific neck pain. Patients with neck complaints existing for two weeks (minimum) till one year (maximum) will participate in the trial. 180 participants will be recruited in thirteen primary health care centres in the Netherlands. The experimental group will be treated with MTU during a six week period. The control group will be treated with physical therapy (standard care, mainly active exercise therapy), also for a period of six weeks. Primary outcomes are Global Perceived Effect (GPE) and functional status (Neck Disability Index (NDI-DV)). Secondary outcomes are neck pain (Numeric Rating Scale (NRS)), Eurocol, costs and quality of life (SF36). Discussion This paper presents details on the rationale of MTU, design, methods and operational aspects of the trial. Trial registration ClinicalTrials.gov Identifier: NCT00713843 PMID:20096136

Adverse event assessment and reporting in trials of newer treatments for post-operative pain.

PubMed

Hoffer, D; Smith, S M; Parlow, J; Allard, R; Gilron, I

2016-08-01

Assessment and reporting of adverse events (AEs) in studies of perioperative interventions is critical given the potential for unintended and preventable iatrogenic morbidity and mortality. This focused review evaluated the quality of AE assessment and reporting in acute post-operative pain treatment trials. Since older analgesics (e.g., opioids, NSAIDs) already have a well-characterized safety profile, we concentrated on trials of pregabalin and gabapentin as a representative sample of studies where the perioperative safety profile was relatively unknown. We reviewed primary reports of trials of pregabalin and gabapentin for treatment of acute post-operative pain for: (1) adherence to the 10 recommendations from the 'CONSORT Extension for Harms,' (2) AE assessment method, (3) timing of AE assessment and reporting, and (4) assessment and reporting of AE severity. We identified 31 trials of pregabalin and 59 of gabapentin. The median number of CONSORT harms recommendations that were satisfied was 7 of 10. The most common (41%) method of AE assessment was direct questioning about specific AEs by investigators. However, AE assessment method was not described in 18% of trials. AE assessments were reported for specified perioperative time points in only 24% of trials. Of greatest concern, no AE data were reported whatsoever in 8 of the included publications. Considerable widespread improvements are needed in AE reporting for post-operative pain treatment trials. In addition to heightened awareness among clinical investigators, mandatory journal editorial policies may further facilitate improvements in safety assessment and reporting. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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

PubMed

Kamijo, Keita; Takeda, Yuji

2013-08-01

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

Amygdala Signaling during Foraging in a Hazardous Environment.

PubMed

Amir, Alon; Lee, Seung-Chan; Headley, Drew B; Herzallah, Mohammad M; Pare, Denis

2015-09-23

We recorded basolateral amygdala (BL) neurons in a seminaturalistic foraging task. Rats had to leave their nest to retrieve food in an elongated arena inhabited by a mechanical predator. There were marked trial-to-trial variations in behavior. After poking their head into the foraging arena and waiting there for a while, rats either retreated to their nest or initiated foraging. Before initiating foraging, rats waited longer on trials that followed failed than successful trials indicating that prior experience influenced behavior. Upon foraging initiation, most principal cells (Type-1) reduced their firing rate, while in a minority (Type-2) it increased. When rats aborted foraging, Type-1 cells increased their firing rates, whereas in Type-2 cells it did not change. Surprisingly, the opposite activity profiles of Type-1 and Type-2 units were also seen in control tasks devoid of explicit threats or rewards. The common correlate of BL activity across these tasks was movement velocity, although an influence of position was also observed. Thus depending on whether rats initiated movement or not, the activity of BL neurons decreased or increased, regardless of whether threat or rewards were present. Therefore, BL activity not only encodes threats or rewards, but is closely related to behavioral output. We propose that higher order cortical areas determine task-related changes in BL activity as a function of reward/threat expectations and internal states. Because Type-1 and Type-2 cells likely form differential connections with the central amygdala (controlling freezing), this process would determine whether movement aimed at attaining food or exploration is suppressed or facilitated. Significance statement: For decades, amygdala research has been dominated by pavlovian and operant conditioning paradigms. This work has led to the view that amygdala neurons signal threats or rewards, in turn causing defensive or approach behaviors. However, the artificial circumstances of conditioning studies bear little resemblance to normal life. In natural conditions, subjects are simultaneously presented with potential threats and rewards, forcing them to engage in a form of risk assessment. We examined this process using a seminaturalistic foraging task. In constant conditions of threats and rewards, amygdala activity could be high or low, depending on the rats' decisions on a given trial. Therefore, amygdala activity does not only encode threats or rewards but is also closely related to behavioral output. Copyright © 2015 the authors 0270-6474/15/3512994-12$15.00/0.

Mitigating residential exposure to secondhand tobacco smoke

NASA Astrophysics Data System (ADS)

Klepeis, Neil E.; Nazaroff, William W.

In a companion paper, we used a simulation model to explore secondhand tobacco smoke (SHS) exposures for typical conditions in residences. In the current paper, we extend this analysis to evaluate the effectiveness of physical mitigation approaches in reducing nonsmokers' exposure to airborne SHS particulate matter in a hypothetical 6-zone house. Measures investigated included closing doors or opening windows in response to smoking activity, modifying location patterns to segregate the nonsmoker and the active smoker, and operating particle filtration devices. We first performed 24 scripted simulation trials using hypothetical patterns of occupant location. We then performed cohort simulation trials across 25 mitigation scenarios using over 1000 pairs of nonsmoker and smoker time-location patterns that were selected from a survey of human activity patterns in US homes. We limited cohort pairs to cases where more than 10 cigarettes were smoked indoors at home each day and the nonsmoker was at home for more than two thirds of the day. We evaluated the effectiveness of each mitigation approach by examining its impact on the simulated frequency distribution of residential SHS particle exposure. The two most effective strategies were the isolation of the smoker in a closed room with an open window, and a ban on smoking whenever the nonsmoker was at home. The use of open windows to supply local or cross ventilation, or the operation of portable filtration devices in smoking rooms, provided moderate exposure reductions. Closed doors, by themselves, were not effective.

An update on equine post-operative ileus: Definitions, pathophysiology and management.

PubMed

Lisowski, Z M; Pirie, R S; Blikslager, A T; Lefebvre, D; Hume, D A; Hudson, N P H

2018-05-01

Post-operative ileus (POI) is a serious condition which any horse undergoing abdominal surgery is at risk of developing, leading to increased hospitalisation time and resulting costs. Advances in the understanding of the development of equine POI are mainly based on human and rodent literature, where manipulation-induced inflammation has been identified as a trigger, with activation of resident muscularis externa macrophages playing a crucial role in the pathophysiology. Despite many pharmacological trials in all species, there is no single completely successful treatment for POI, highlighting that the condition is multifactorial in cause and requires a multimodal approach to minimise its incidence. © 2017 EVJ Ltd.

A Critical Review: Management and Surgical Options for Articular Defects in the Hip.

PubMed

Makhni, Eric C; Stone, Austin V; Ukwuani, Gift C; Zuke, William; Garabekyan, Tigran; Mei-Dan, Omer; Nho, Shane J

2017-07-01

Patients with articular cartilage lesions of the hip may present with pain and symptoms that may be vague in nature and onset. Therefore, a thorough history and physical examination should be performed for every patient presenting with hip pain and/or disability. The management may be operative or nonoperative. Nonoperative management includes a trial of rest and/or activity modification, along with anti-inflammatory medications, physical therapy, and biologic injections. Operative treatment in the form of arthroscopic techniques continues to decrease morbidity and offer innovative solutions and new applications for microfracture, ACT, and AMIC. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term outcome study of growth factor-treated pressure ulcers.

PubMed

Payne, W G; Ochs, D E; Meltzer, D D; Hill, D P; Mannari, R J; Robson, L E; Robson, M C

2001-01-01

Exogenous application of growth factors have been reported in an attempt to accelerate healing of chronic wounds. Most of the trials were of brief duration with short to no follow-up periods. Long-term outcome studies are sparse for pressure ulcer therapies with success rates around 30% for both operative and nonoperative treatments. Follow-up evaluations were performed serially up to 12 months for patients completing a 35 day blinded, placebo-controlled cytokine clinical trial of pressure ulcers. Fifty-four of 61 patients completed the follow-up period with 68.5% of the patients (37 of 54) being healed after 1 year. Of patients healing > or =85% during the active treatment phase, 84.6% were healed after 1 year compared with 61% of those that healed <85% during treatment (P <0.05). Long-term outcome was better in this growth factor trial than with surgical or standard nonoperative treatment of pressure ulcers. Since only patients receiving exogenously applied cytokines achieved >85% closure during the treatment phase of the trial, the excellent long-term outcome appears attributable to the cytokine therapy.

Quantifying and visualizing site performance in clinical trials.

PubMed

Yang, Eric; O'Donovan, Christopher; Phillips, JodiLyn; Atkinson, Leone; Ghosh, Krishnendu; Agrafiotis, Dimitris K

2018-03-01

One of the keys to running a successful clinical trial is the selection of high quality clinical sites, i.e., sites that are able to enroll patients quickly, engage them on an ongoing basis to prevent drop-out, and execute the trial in strict accordance to the clinical protocol. Intuitively, the historical track record of a site is one of the strongest predictors of its future performance; however, issues such as data availability and wide differences in protocol complexity can complicate interpretation. Here, we demonstrate how operational data derived from central laboratory services can provide key insights into the performance of clinical sites and help guide operational planning and site selection for new clinical trials. Our methodology uses the metadata associated with laboratory kit shipments to clinical sites (such as trial and anonymized patient identifiers, investigator names and addresses, sample collection and shipment dates, etc.) to reconstruct the complete schedule of patient visits and derive insights about the operational performance of those sites, including screening, enrollment, and drop-out rates and other quality indicators. This information can be displayed in its raw form or normalized to enable direct comparison of site performance across studies of varied design and complexity. Leveraging Covance's market leadership in central laboratory services, we have assembled a database of operational metrics that spans more than 14,000 protocols, 1400 indications, 230,000 unique investigators, and 23 million patient visits and represents a significant fraction of all clinical trials run globally in the last few years. By analyzing this historical data, we are able to assess and compare the performance of clinical investigators across a wide range of therapeutic areas and study designs. This information can be aggregated across trials and geographies to gain further insights into country and regional trends, sometimes with surprising results. The use of operational data from Covance Central Laboratories provides a unique perspective into the performance of clinical sites with respect to many important metrics such as patient enrollment and retention. These metrics can, in turn, be used to guide operational planning and site selection for new clinical trials, thereby accelerating recruitment, improving quality, and reducing cost.

Field Trial of the Enhanced Data Authentication System (EDAS)

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

Thomas, Maikael A.; Baldwin, George T.; Hymel, Ross W.

2016-05-01

The goal of the field trial of EDAS was to demonstrate the utility of secure branching of operator instrumentation for nuclear safeguards, identify any unforeseen implementation and application issues with EDAS, and confirm whether the approach is compatible with operator concerns and constraints.

Involving older people in a multi-centre randomised trial of a complex intervention in pre-hospital emergency care: implementation of a collaborative model.

PubMed

Koniotou, Marina; Evans, Bridie Angela; Chatters, Robin; Fothergill, Rachael; Garnsworthy, Christopher; Gaze, Sarah; Halter, Mary; Mason, Suzanne; Peconi, Julie; Porter, Alison; Siriwardena, A Niroshan; Toghill, Alun; Snooks, Helen

2015-07-10

Health services research is expected to involve service users as active partners in the research process, but few examples report how this has been achieved in practice in trials. We implemented a model to involve service users in a multi-centre randomised controlled trial in pre-hospital emergency care. We used the generic Standard Operating Procedure (SOP) from our Clinical Trials Unit (CTU) as the basis for creating a model to fit the context and population of the SAFER 2 trial. In our model, we planned to involve service users at all stages in the trial through decision-making forums at 3 levels: 1) strategic; 2) site (e.g. Wales; London; East Midlands); 3) local. We linked with charities and community groups to recruit people with experience of our study population. We collected notes of meetings alongside other documentary evidence such as attendance records and study documentation to track how we implemented our model. We involved service users at strategic, site and local level. We also added additional strategic level forums (Task and Finish Groups and Writing Days) where we included service users. Service user involvement varied in frequency and type across meetings, research stages and locations but stabilised and increased as the trial progressed. Involving service users in the SAFER 2 trial showed how it is feasible and achievable for patients, carers and potential patients sharing the demographic characteristics of our study population to collaborate in a multi-centre trial at the level which suited their health, location, skills and expertise. A standard model of involvement can be tailored by adopting a flexible approach to take account of the context and complexities of a multi-site trial. Current Controlled Trials ISRCTN60481756. Registered: 13 March 2009.

Envelope Responses in Single-Trial EEG Indicate Attended Speaker in a Cocktail Party

DTIC Science & Technology

2013-06-20

users to modulate their brain activity, such as motor rhythms, in order to signal intent [13], but these often require considerable training . Other...BCIs forgo training and instead have subjects make choices by attending to one of multiple visual and/or auditory stimuli. By presenting each stimulus...modulated). An envelope-based BCI could operate on more naturalistic auditory stimuli, such as speech or music . For example, an envelope-based BCI

A Multisite, Randomized Clinical Trial of Virtual Reality and Prolonged Exposure Therapy for Active Duty Soldiers with PTSD

DTIC Science & Technology

2015-02-01

Department of Defense, Washington Headquarters Services , Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite...1204, Arlington, VA 22202- 4302. Respondents should be aware that notwithstanding any other provision of law , no person shall be subject to any...conducted for both treatments. Service members were assessed before randomization, after 5 sessions, at posttreatment, and 3- and 6-months posttreatment

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

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

PubMed Central

2010-01-01

Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676 PMID:20398378

Use of an embedded, micro-randomised trial to investigate non-compliance in telehealth interventions.

PubMed

Law, Lisa M; Edirisinghe, Nuwani; Wason, James Ms

2016-08-01

Many types of telehealth interventions rely on activity from the patient in order to have a beneficial effect on their outcome. Remote monitoring systems require the patient to record regular measurements at home, for example, blood pressure, so clinicians can see whether the patient's health changes over time and intervene if necessary. A big problem in this type of intervention is non-compliance. Most telehealth trials report compliance rates, but they rarely compare compliance among various options of telehealth delivery, of which there may be many. Optimising telehealth delivery is vital for improving compliance and, therefore, clinical outcomes. We propose a trial design which investigates ways of improving compliance. For efficiency, this trial is embedded in a larger trial for evaluating clinical effectiveness. It employs a technique called micro-randomisation, where individual patients are randomised multiple times throughout the study. The aims of this article are (1) to verify whether the presence of an embedded secondary trial still allows valid analysis of the primary research and (2) to demonstrate the usefulness of the micro-randomisation technique for comparing compliance interventions. Simulation studies were used to simulate a large number of clinical trials, in which no embedded trial was used, a micro-randomised embedded trial was used, and a factorial embedded trial was used. Each simulation recorded the operating characteristics of the primary and secondary trials. We show that the type I error rate of the primary analysis was not affected by the presence of an embedded secondary trial. Furthermore, we show that micro-randomisation is superior to a factorial design as it reduces the variation caused by within-patient correlation. It therefore requires smaller sample sizes - our simulations showed a requirement of 128 patients for a micro-randomised trial versus 760 patients for a factorial design, in the presence of within-patient correlation. We believe that an embedded, micro-randomised trial is a feasible technique that can potentially be highly useful in telehealth trials. © The Author(s) 2016.

Hypothesis Sampling Systems among Preoperational and Concrete Operational Kindergarten Children

ERIC Educational Resources Information Center

Gholson, Barry; And Others

1976-01-01

Preoperational and concrete operational kindergarten children received stimulus differentiation training, either with or without feedback, and then a series of discrimination learning problems in which a blank trial probe was used to detect a child's hypothesis after each feedback trial. Piagetian stage theory requires elaboration to account…

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

PubMed

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

2011-07-01

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

Pre-operative interventions (non-surgical and non-pharmacological) for patients with hip or knee osteoarthritis awaiting joint replacement surgery--a systematic review and meta-analysis.

PubMed

Wallis, Jason A; Taylor, Nicholas F

2011-12-01

To determine if pre-operative interventions for hip and knee osteoarthritis provide benefit before and after joint replacement. Systematic review with meta-analysis of randomised controlled trials (RCTs) of pre-operative interventions for people with hip or knee osteoarthritis awaiting joint replacement surgery. Standardised mean differences (SMD) were calculated for pain, musculoskeletal impairment, activity limitation, quality of life, and health service utilisation (length of stay and discharge destination). The GRADE approach was used to determine the quality of the evidence. Twenty-three RCTs involving 1461 participants awaiting hip or knee replacement surgery were identified. Meta-analysis provided moderate quality evidence that pre-operative exercise interventions for knee osteoarthritis reduced pain prior to knee replacement surgery (SMD (95% CI)=0.43 [0.13, 0.73]). None of the other meta-analyses investigating pre-operative interventions for knee osteoarthritis demonstrated any effect. Meta-analyses provided low to moderate quality evidence that exercise interventions for hip osteoarthritis reduced pain (SMD (95% CI)=0.52 [0.04, 1.01]) and improved activity (SMD (95% CI)=0.47 [0.11, 0.83]) prior to hip replacement surgery. Meta-analyses provided low quality evidence that exercise with education programs improved activity after hip replacement with reduced time to reach functional milestones during hospital stay (e.g., SMD (95% CI)=0.50 [0.10, 0.90] for first day walking). Low to moderate evidence from mostly small RCTs demonstrated that pre-operative interventions, particularly exercise, reduce pain for patients with hip and knee osteoarthritis prior to joint replacement, and exercise with education programs may improve activity after hip replacement. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effects of audiovisual distraction in children with special healthcare needs during dental restorations: a randomized crossover clinical trial.

PubMed

Bagattoni, Simone; D'Alessandro, Giovanni; Sadotti, Agnese; Alkhamis, Nadia; Piana, Gabriela

2018-01-01

Audiovisual distraction using video eyeglasses is useful in managing distress and reducing fear and anxiety in healthy children during dental treatments. To evaluate the effect of audiovisual distraction on behavior and self-reported pain of children with special healthcare needs (SHCN) without intellectual disability during dental restorations and its influence on the operator stress and the time of the appointment. This randomized controlled crossover trial comprised 48 children with SHCN requiring at least two dental restorations. One restoration was done wearing the video eyeglasses and one wearing conventional behavior management techniques. Subjective and objective pain was evaluated using the Faces Pain Scale - Revised (FPS-R) and the revised Face, Leg, Activity, Cry, and Consolability scale (r-FLACC). The operator stress using a VAS, the time of the appointment, and the child satisfaction were recorded. The use of video eyeglasses significantly reduced the operator stress. The bivariate analysis showed that the mean FPS-R score and the mean r-FLACC score were significantly lower using the video eyeglasses only during the second clinical session. Audiovisual distraction could be useful in managing distress in SHCN children without intellectual disability but cannot replace the conventional behavior management techniques. © 2017 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neural Substrates for Judgment of Self-Agency in Ambiguous Situations

PubMed Central

Fukushima, Hirokata; Goto, Yurie; Maeda, Takaki; Kato, Motoichiro; Umeda, Satoshi

2013-01-01

The sense of agency is the attribution of oneself as the cause of one’s own actions and their effects. Accurate agency judgments are essential for adaptive behaviors in dynamic environments, especially in conditions of uncertainty. However, it is unclear how agency judgments are made in ambiguous situations where self-agency and non-self-agency are both possible. Agency attribution is thus thought to require higher-order neurocognitive processes that integrate several possibilities. Furthermore, neural activity specific to self-attribution, as compared with non-self-attribution, may reflect higher-order critical operations that contribute to constructions of self-consciousness. Based on these assumptions, the present study focused on agency judgments under ambiguous conditions and examined the neural correlates of this operation with functional magnetic resonance imaging. Participants performed a simple but demanding agency-judgment task, which required them to report on whether they attributed their own action as the cause of a visual stimulus change. The temporal discrepancy between the participant’s action and the visual events was adaptively set to be maximally ambiguous for each individual on a trial-by-trial basis. Comparison with results for a control condition revealed that the judgment of agency was associated with activity in lateral temporo-parietal areas, medial frontal areas, the dorsolateral prefrontal area, and frontal operculum/insula regions. However, most of these areas did not differentiate between self- and non-self-attribution. Instead, self-attribution was associated with activity in posterior midline areas, including the precuneus and posterior cingulate cortex. These results suggest that deliberate self-attribution of an external event is principally associated with activity in posterior midline structures, which is imperative for self-consciousness. PMID:23977268

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

PubMed

Carskadon, Mary A; Herz, Rachel S

2004-05-01

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

40 CFR 265.402 - Waste analysis and trial tests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility.] ... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Chemical, Physical, and Biological Treatment § 265.402 Waste analysis and trial tests...

40 CFR 265.402 - Waste analysis and trial tests.

Code of Federal Regulations, 2014 CFR

2014-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility.] ... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Chemical, Physical, and Biological Treatment § 265.402 Waste analysis and trial tests...

40 CFR 265.402 - Waste analysis and trial tests.

Code of Federal Regulations, 2012 CFR

2012-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility.] ... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Chemical, Physical, and Biological Treatment § 265.402 Waste analysis and trial tests...

40 CFR 265.402 - Waste analysis and trial tests.

Code of Federal Regulations, 2010 CFR

2010-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility.] ... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Chemical, Physical, and Biological Treatment § 265.402 Waste analysis and trial tests...

40 CFR 265.402 - Waste analysis and trial tests.

Code of Federal Regulations, 2011 CFR

2011-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility.] ... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Chemical, Physical, and Biological Treatment § 265.402 Waste analysis and trial tests...

Overview of different available chemotherapy regimens combined with radiotherapy for the neoadjuvant and definitive treatment of esophageal cancer.

PubMed

Tomasello, Gianluca; Ghidini, Michele; Barni, Sandro; Passalacqua, Rodolfo; Petrelli, Fausto

2017-06-01

Neoadjuvant chemoradiotherapy (CTRT) is the current standard of care for treatment of locally advanced cancer of the esophagus or gastroesophageal junction. Many efforts have been made over the last years to identify the best chemotherapy and radiotherapy combination regimen, but specific randomized trials addressing this issue are still lacking. Areas covered: A systematic review of the literature was performed searching in PubMed all published studies of combinations CTRT regimens for operable or unresectable esophageal cancer to describe activity and toxicity. Studies considered were prospective series or clinical phase II-III trials including at least 40 patients and published in English language. Expert commentary: Long-term results of CROSS trial have established RT combined with carboplatin plus paclitaxel chemotherapy as the preferred neoadjuvant treatment option for both squamous and adenocarcinoma of the esophagus. More effective multimodal treatment strategies integrating novel biological agents including immunotherapy and based on an extensive molecular tumor characterization are eagerly awaited.

A Randomized Controlled Trial of In-Home Tele-behavioral Health Care Utilizing Behavioral Activation for Depression

DTIC Science & Technology

2015-03-01

health, primary care, and operational medicine service programs at JBLM and PVA (e.g., psychologists, psychiatrists, physicians, social workers, nurse ...practitioners, and nurses ). Military chaplains on JBLM also serve as a recruitment source. These referring professionals are not affiliated with the...session early? YES a. lfyes, explain: 3. Was the session rescheduled ? YES NO (cir a. lf yes, who was it rescheduled by? 4. Did the participant miss

Implementation of multifamily group treatment for veterans with traumatic brain injury.

PubMed

Perlick, Deborah A; Straits-Troster, Kristy; Strauss, Jennifer L; Norell, Diane; Tupler, Larry A; Levine, Bruce; Luo, Xiaodong; Holman, Caroline; Marcus, Tara; Dixon, Lisa B; Dyck, Dennis G

2013-06-01

This study evaluated the initial efficacy and feasibility of implementing multifamily group treatment for veterans with traumatic brain injury (TBI). Veterans at two Veterans Affairs medical centers were prescreened by their providers for participation in an open trial of multifamily group treatment for TBI. Enrollment was limited to consenting veterans with a clinical diagnosis of TBI sustained during the Operation Enduring Freedom-Operation Iraqi Freedom era, a family member or partner consenting to participate, and a score ≥20 on the Mini-Mental State Examination. The nine-month (April 2010-March 2011) trial consisted of individual family sessions, an educational workshop, and bimonthly multifamily problem-solving sessions. Interpersonal functioning and symptomatic distress among veterans and family burden, empowerment, and symptomatic distress among families were assessed before and after treatment. Providers referred 34 (58%) of 59 veterans screened for the study; of those, 14 (41%) met criteria and consented to participate, and 11 (32%) completed the study. Severity of TBI, insufficient knowledge about the benefits of family involvement, and access problems influenced decisions to exclude veterans or refuse to participate. Treatment was associated with decreased veteran anger expression (p≤.01) and increased social support and occupational activity (p≤.05), with effect sizes ranging from .6 to 1.0. Caregivers reported decreased burden (p≤.05) and increased empowerment (p≤.01). The results supported implementation of a randomized controlled trial, building in education at the provider and family level.

Flavonoids to reduce bleeding and pain after stapled hemorrhoidopexy: a randomized controlled trial.

PubMed

Mlakar, Bostjan; Kosorok, Pavle

2005-08-01

Control of postoperative symptoms is of paramount importance in ambulatory surgery. This trial was conducted to evaluate whether a micronized purified flavonoid fraction (MPFF) (Detralex((R))) reduces postoperative bleeding, pain and consumption of analgesics after ambulatory stapled hemorrhoidopexy, as reported in trials after classic hemorrhoidectomy. Phlebotropic activity, protective effect on the capillaries and anti-inflammatory properties of this drug have been reported in several studies. Sixty-three patients with third-degree hemorrhoids had ambulatory stapled hemorrhoidopexy under spinal anesthesia in the period of one year. The patients were randomized, with 30 receiving Detralex 500 mg (2 tablets 3 times daily for 5 days after the operation) and 33 forming the control group. The patients were asked to daily self-assess the presence of blood on defecation, degree of pain and consumption of analgesics for the first week after the operation. There was no significant difference between the two groups in duration of presence of blood, degree of pain or analgesics requirement. No major complications, such as bleeding requiring transfusion or hospitalization, sepsis, anal stenosis or urgent defecation, were noted in the follow-up period. There were no side effects from Detralex treatment. In our study we could not demonstrate any positive effect of prescribing flavonoids after stapler hemorrhoidopexy. This procedure may not be sufficiently aggressive and is associated with too few postoperative complications to show any protective influence of flavonoids.

Industrial trials of low-expansivity sawblades

Treesearch

Jeanne D. Danielson; Frank J. Worzala

1992-01-01

Low-expansivity alloys have the potential to reduce thermal instability of sawblades during the sawing operation. In preliminary industrial trials of sawblades made of low-expansivity alloy, sawing accuracy was improved 22 to 38 percent during normal sawing. When saws made of a low-expansivity alloy were operated with a large temperature gradient across the blade,...

Wearable activity monitors in oncology trials: Current use of an emerging technology.

PubMed

Gresham, Gillian; Schrack, Jennifer; Gresham, Louise M; Shinde, Arvind M; Hendifar, Andrew E; Tuli, Richard; Rimel, B J; Figlin, Robert; Meinert, Curtis L; Piantadosi, Steven

2018-01-01

Physical activity is an important outcome in oncology trials. Physical activity is commonly assessed using self-reported questionnaires, which are limited by recall and response biases. Recent advancements in wearable technology have provided oncologists with new opportunities to obtain real-time, objective physical activity data. The purpose of this review was to describe current uses of wearable activity monitors in oncology trials. We searched Pubmed, Embase, and the Cochrane Central Register of Controlled Trials for oncology trials involving wearable activity monitors published between 2005 and 2016. We extracted details on study design, types of activity monitors used, and purpose for their use. We summarized activity monitor metrics including step counts, sleep and sedentary time, and time spent in moderate-to-vigorous activity. We identified 41 trials of which 26 (63%) involved cancer survivors (post-treatment) and 15 trials (37%) involved patients with active cancer. Most trials (65%) involved breast cancer patients. Wearable activity monitors were commonly used in exercise (54%) or behavioral (29%) trials. Cancer survivors take between 4660 and 11,000 steps/day and those undergoing treatment take 2885 to 8300steps/day. Wearable activity monitors are increasingly being used to obtain objective measures of physical activity in oncology trials. There is potential for their use to expand to evaluate and predict clinical outcomes such as survival, quality of life, and treatment tolerance in future studies. Currently, there remains a lack of standardization in the types of monitors being used and how their data are being collected, analyzed, and interpreted. Recent advancements in wearable activity monitor technology have provided oncologists with new opportunities to monitor their patients' daily activity in real-world settings. The integration of wearable activity monitors into cancer care will help increase our understanding of the associations between physical activity and the prevention and management of the disease, in addition to other important cancer outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Field trial of applicability of lot quality assurance sampling survey method for rapid assessment of prevalence of active trachoma.

PubMed Central

Myatt, Mark; Limburg, Hans; Minassian, Darwin; Katyola, Damson

2003-01-01

OBJECTIVE: To test the applicability of lot quality assurance sampling (LQAS) for the rapid assessment of the prevalence of active trachoma. METHODS: Prevalence of active trachoma in six communities was found by examining all children aged 2-5 years. Trial surveys were conducted in these communities. A sampling plan appropriate for classifying communities with prevalences < or =20% and > or =40% was applied to the survey data. Operating characteristic and average sample number curves were plotted, and screening test indices were calculated. The ability of LQAS to provide a three-class classification system was investigated. FINDINGS: Ninety-six trial surveys were conducted. All communities with prevalences < or =20% and > or =40% were identified correctly. The method discriminated between communities with prevalences < or =30% and >30%, with sensitivity of 98% (95% confidence interval (CI)=88.2-99.9%), specificity of 84.4% (CI=69.9-93.0%), positive predictive value of 87.7% (CI=75.7-94.5%), negative predictive value of 97.4% (CI=84.9-99.9%), and accuracy of 91.7% (CI=83.8-96.1%). Agreement between the three prevalence classes and survey classifications was 84.4% (CI=75.2-90.7%). The time needed to complete the surveys was consistent with the need to complete a survey in one day. CONCLUSION: Lot quality assurance sampling provides a method of classifying communities according to the prevalence of active trachoma. It merits serious consideration as a replacement for the assessment of the prevalence of active trachoma with the currently used trachoma rapid assessment method. It may be extended to provide a multi-class classification method. PMID:14997240

Average is optimal: an inverted-U relationship between trial-to-trial brain activity and behavioral performance.

PubMed

He, Biyu J; Zempel, John M

2013-01-01

It is well known that even under identical task conditions, there is a tremendous amount of trial-to-trial variability in both brain activity and behavioral output. Thus far the vast majority of event-related potential (ERP) studies investigating the relationship between trial-to-trial fluctuations in brain activity and behavioral performance have only tested a monotonic relationship between them. However, it was recently found that across-trial variability can correlate with behavioral performance independent of trial-averaged activity. This finding predicts a U- or inverted-U- shaped relationship between trial-to-trial brain activity and behavioral output, depending on whether larger brain variability is associated with better or worse behavior, respectively. Using a visual stimulus detection task, we provide evidence from human electrocorticography (ECoG) for an inverted-U brain-behavior relationship: When the raw fluctuation in broadband ECoG activity is closer to the across-trial mean, hit rate is higher and reaction times faster. Importantly, we show that this relationship is present not only in the post-stimulus task-evoked brain activity, but also in the pre-stimulus spontaneous brain activity, suggesting anticipatory brain dynamics. Our findings are consistent with the presence of stochastic noise in the brain. They further support attractor network theories, which postulate that the brain settles into a more confined state space under task performance, and proximity to the targeted trajectory is associated with better performance.

Signal detection in animal psychoacoustics: Analysis and simulation of sensory and decision-related influences

PubMed Central

Alves-Pinto, A.; Sollini, J.; Sumner, C.J.

2012-01-01

Signal detection theory (SDT) provides a framework for interpreting psychophysical experiments, separating the putative internal sensory representation and the decision process. SDT was used to analyse ferret behavioural responses in a (yes–no) tone-in-noise detection task. Instead of measuring the receiver-operating characteristic (ROC), we tested SDT by comparing responses collected using two common psychophysical data collection methods. These (Constant Stimuli, Limits) differ in the set of signal levels presented within and across behavioural sessions. The results support the use of SDT as a method of analysis: SDT sensory component was unchanged between the two methods, even though decisions depended on the stimuli presented within a behavioural session. Decision criterion varied trial-by-trial: a ‘yes’ response was more likely after a correct rejection trial than a hit trial. Simulation using an SDT model with several decision components reproduced the experimental observations accurately, leaving only ∼10% of the variance unaccounted for. The model also showed that trial-by-trial dependencies were unlikely to influence measured psychometric functions or thresholds. An additional model component suggested that inattention did not contribute substantially. Further analysis showed that ferrets were changing their decision criteria, almost optimally, to maximise the reward obtained in a session. The data suggest trial-by-trial reward-driven optimization of the decision process. Understanding the factors determining behavioural responses is important for correlating neural activity and behaviour. SDT provides a good account of animal psychoacoustics, and can be validated using standard psychophysical methods and computer simulations, without recourse to ROC measurements. PMID:22698686

Meta-analysis of Prolene Hernia System mesh versus Lichtenstein mesh in open inguinal hernia repair.

PubMed

Sanjay, Pandanaboyana; Watt, David G; Ogston, Simon A; Alijani, Afshin; Windsor, John A

2012-10-01

This study was designed to systematically analyse all published randomized clinical trials comparing the Prolene Hernia System (PHS) mesh and Lichtenstein mesh for open inguinal hernia repair. A literature search was performed using the Cochrane Colorectal Cancer Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase and Science Citation Index Expanded. Randomized trials comparing the Lichtenstein Mesh repair (LMR) with the Prolene Hernia System were included. Statistical analysis was performed using Review Manager Version 5.1 software. The primary outcome measures were hernia recurrence and chronic pain after operation. Secondary outcome measures included surgical time, peri-operative complications, time to return to work, early and long-term postoperative complications. Six randomized clinical trials were identified as suitable, containing 1313 patients. There was no statistical difference between the two types of repair in operation time, time to return to work, incidence of chronic groin pain, hernia recurrence or long-term complications. The PHS group had a higher rate of peri-operative complications, compared to Lichtenstein mesh repair (risk ratio (RR) 0.71, 95% confidence interval 0.55-0.93, P=0.01). The use of PHS mesh was associated with an increased risk of peri-operative complications compared to LMR. Both mesh repair techniques have comparable short- and long-term outcomes. Copyright © 2012 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Electronic Clinical Trial Protocol Distribution via the World-Wide Web

PubMed Central

Afrin, Lawrence B.; Kuppuswamy, Valarmathi; Slater, Barbara; Stuart, Robert K.

1997-01-01

Clinical trials today typically are inefficient, paper-based operations. Poor community physician awareness of available trials and difficult referral mechanisms also contribute to poor accrual. The Physicians Research Network (PRN) web was developed for more efficient trial protocol distribution and eligibility inquiries. The Medical University of South Carolina's Hollings Cancer Center trials program and two community oncology practices served as a testbed. In 581 man-hours over 18 months, 147 protocols were loaded into PRN. The trials program eliminated all protocol hardcopies except the masters, reduced photocopier use 59%, and saved 1.0 full-time equivalents (FTE), but 1.0 FTE was needed to manage PRN. There were no known security breaches, downtime, or content-related problems. Therefore, PRN is a paperless, user-preferred, reliable, secure method for distributing protocols and reducing distribution errors and delays because only a single copy of each protocol is maintained. Furthermore, PRN is being extended to serve other aspects of trial operations. PMID:8988471

Paint-only is equivalent to scrub-and-paint in preoperative preparation of abdominal surgery sites.

PubMed

Ellenhorn, Joshua D I; Smith, David D; Schwarz, Roderich E; Kawachi, Mark H; Wilson, Timothy G; McGonigle, Kathryn F; Wagman, Lawrence D; Paz, I Benjamin

2005-11-01

Antiseptic preoperative skin site preparation is used to prepare the operative site before making a surgical incision. The goal of this preparation is a reduction in postoperative wound infection. The most straightforward technique necessary to achieve this goal remains controversial. A prospective randomized trial was designed to prove equivalency for two commonly used techniques of surgical skin site preparation. Two hundred thirty-four patients undergoing nonlaparoscopic abdominal operations were consented for the trial. Exclusion criteria included presence of active infection at the time of operation, neutropenia, history of skin reaction to iodine, or anticipated insertion of prosthetic material at the time of operation. Patients were randomized to receive either a vigorous 5-minute scrub with povidone-iodine soap, followed by absorption with a sterile towel, and a paint with aqueous povidone-iodine or surgical site preparation with a povidone-iodine paint only. The primary end point of the study was wound infection rate at 30 days, defined as presence of clinical signs of infection requiring therapeutic intervention. Patients randomized to the scrub-and-paint arm (n = 115) and the paint-only arm (n = 119) matched at baseline with respect to age, comorbidity, wound classification, mean operative time, placement of drains, prophylactic antibiotic use, and surgical procedure (all p > 0.09). Wound infection occurred in 12 (10%) scrub-and-paint patients, and 12 (10%) paint-only patients. Based on our predefined equivalency parameters, we conclude equivalence of infection rates between the two preparations. Preoperative preparation of the abdomen with a scrub with povidone-iodine soap followed by a paint with aqueous povidone-iodine can be abandoned in favor of a paint with aqueous povidone-iodine alone. This change will result in reductions in operative times and costs.

Neural mechanisms of interference control in working memory: effects of interference expectancy and fluid intelligence.

PubMed

Burgess, Gregory C; Braver, Todd S

2010-09-20

A critical aspect of executive control is the ability to limit the adverse effects of interference. Previous studies have shown activation of left ventrolateral prefrontal cortex after the onset of interference, suggesting that interference may be resolved in a reactive manner. However, we suggest that interference control may also operate in a proactive manner to prevent effects of interference. The current study investigated the temporal dynamics of interference control by varying two factors - interference expectancy and fluid intelligence (gF) - that could influence whether interference control operates proactively versus reactively. A modified version of the recent negatives task was utilized. Interference expectancy was manipulated across task blocks by changing the proportion of recent negative (interference) trials versus recent positive (facilitation) trials. Furthermore, we explored whether gF affected the tendency to utilize specific interference control mechanisms. When interference expectancy was low, activity in lateral prefrontal cortex replicated prior results showing a reactive control pattern (i.e., interference-sensitivity during probe period). In contrast, when interference expectancy was high, bilateral prefrontal cortex activation was more indicative of proactive control mechanisms (interference-related effects prior to the probe period). Additional results suggested that the proactive control pattern was more evident in high gF individuals, whereas the reactive control pattern was more evident in low gF individuals. The results suggest the presence of two neural mechanisms of interference control, with the differential expression of these mechanisms modulated by both experimental (e.g., expectancy effects) and individual difference (e.g., gF) factors.

Multidisciplinary rehabilitation for subacute low back pain: graded activity or workplace intervention or both? A randomized controlled trial.

PubMed

Anema, Johannes R; Steenstra, Ivan A; Bongers, Paulien M; de Vet, Henrica C W; Knol, Dirk L; Loisel, Patrick; van Mechelen, Willem

2007-02-01

Population-based randomized controlled trial. To assess the effectiveness of workplace intervention and graded activity, separately and combined, for multidisciplinary rehabilitation of low back pain (LBP). Effective components for multidisciplinary rehabilitation of LBP are not yet established. Participants sick-listed 2 to 6 weeks due to nonspecific LBP were randomized to workplace intervention (n = 96) or usual care (n = 100). Workplace intervention consisted of workplace assessment, work modifications, and case management involving all stakeholders. Participants still sick-listed at 8 weeks were randomized for graded activity (n = 55) or usual care (n = 57). Graded activity comprised biweekly 1-hour exercise sessions based on operant-conditioning principles. Outcomes were lasting return to work, pain intensity and functional status, assessed at baseline, and at 12, 26, and 52 weeks after the start of sick leave. Time until return to work for workers with workplace intervention was 77 versus 104 days (median) for workers without this intervention (P = 0.02). Workplace intervention was effective on return to work (hazard ratio = 1.7; 95% CI, 1.2-2.3; P = 0.002). Graded activity had a negative effect on return to work (hazard ratio = 0.4; 95% CI, 0.3-0.6; P < 0.001) and functional status. Combined intervention had no effect. Workplace intervention is advised for multidisciplinary rehabilitation of subacute LBP. Graded activity or combined intervention is not advised.

Evaluation of a training program for device operators in the Australian Government's Point of Care Testing in General Practice Trial: issues and implications for rural and remote practices.

PubMed

Shephard, Mark D; Mazzachi, Beryl C; Watkinson, Les; Shephard, Anne K; Laurence, Caroline; Gialamas, Angela; Bubner, Tanya

2009-01-01

From September 2005 to February 2007 the Australian Government funded the Point of Care Testing (PoCT) in General Practice Trial, a multi-centre, cluster randomised controlled trial to determine the safety, clinical effectiveness, cost-effectiveness and satisfaction of PoCT in General Practice. In total, 53 practices (23 control and 30 intervention) based in urban, rural or remote locations across three states (South Australia [SA], New South Wales [NSW] and Victoria [VIC]) participated in the Trial. Control practices had pathology testing performed by their local laboratory, while intervention practices conducted pathology testing by PoCT. In total, 4968 patients (1958 control and 3010 intervention) participated in the Trial. The point-of-care (PoC) tests performed by intervention practices were: haemoglobin A1c (HbA1c) and urine albumin:creatinine ratio (ACR) on patients with diabetes, total cholesterol, triglyceride and high density lipoprotein (HDL) cholesterol on patients with hyperlipidaemia, and international normalised ratio (INR) on patients on anticoagulant therapy. Three PoCT devices measured these tests: the Siemens DCA 2000 (Siemens HealthCare Diagnostics, Melbourne, VIC, Australia) for HbA1c and urine ACR; Point of Care Diagnostics Cholestech LDX analyser (Point of Care Diagnostics; Sydney, NSW, Australia) for lipids; and the Roche CoaguChek S (Roche Diagnostics; Sydney, NSW, Australia) for INR. Point-of-care testing in the General Practice Trial was underpinned by a quality management framework which included an on-going training and competency program for PoCT device operators. This article describes the design, implementation and results of the training and competency program. An education and training resource package was developed for the Trial consisting of a training manual, a set of A3 laminated posters and a CD ROM. Five initial training workshops were held for intervention practices from each geographic region between August and October 2005 at three centres - Adelaide (SA), Bendigo (VIC) and Dubbo (NSW). These workshops combined theoretical training in the principles and practice of PoCT with 'hands on' practical training delivered in interactive small group sessions. At the completion of training, practice staff undertook a written and practical competency assessment and received a certificate of competency as a qualified device operator. Following each initial training workshop, practice staff completed a short satisfaction survey. Five refresher training workshops covering all geographic regions were delivered during late August 2006, coinciding with the 12 month point of the live phase of the Trial. At the completion of the Trial in February 2007, device operators completed a further questionnaire. Sixty device operators from 31 practices completed training and competency assessment as part of the Initial Training Workshop series. A further 20 device operators from 12 of the practices were trained in the 12 month period after the initial workshops; 19 of these staff were from rural or remote practices. In total 80 device operators comprising 74 practice staff and six GPs from 31 practices were trained and received competency certificates as part of Trial. In all, 19 device operators left the Trial either through personal resignation from an existing practice or because their practice withdrew from the Trial; the majority (84%) were from rural and remote practices. A total of 42 device operators from 25 practices attended refresher training in the second half of 2006. Results from the satisfaction questionnaire completed by device operators following the initial training workshops showed there was unanimous agreement that the posters were useful for the conduct of daily PoCT and practical training in small groups was satisfactory as a training method. The quality and appropriateness of the PoCT training resources and the workshop overall was rated as either good or excellent by all respondents (100% and 78%, respectively). The responses by device operators to the post-Trial satisfaction questionnaire found a high level of satisfaction with PoCT across all geographic regions. Device operators from remote practices had the highest satisfaction levels for quality of training, usefulness of the training manual, ease of use of devices, confidence in the accuracy of PoCT results and preference for PoCT over laboratory testing. The usefulness of the posters for conducting PoCT achieved the highest satisfaction rating among operators from all three geographic regions. However the highest staff turnover rates and the highest number of requests for training of additional staff were from rural and remote practices. The methods established for the implementation and delivery of training and competency assessment for the PoCT in General Practice Trial were appropriate and effective. Results of the evaluation showed rural and remote practices have a greater need for training and support compared to their urban counterparts and may require more flexible training options to cater for much higher rates of staff turnover.

40 CFR 265.200 - Waste analysis and trial tests.

Code of Federal Regulations, 2010 CFR

2010-07-01

... operator to place the results from each waste analysis and trial test, or the documented information, in... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Tank Systems § 265.200 Waste analysis and trial tests. In addition to performing the...

40 CFR 265.225 - Waste analysis and trial tests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Surface Impoundments § 265.225 Waste analysis and trial tests. (a) In addition to the...

40 CFR 265.225 - Waste analysis and trial tests.

Code of Federal Regulations, 2010 CFR

2010-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Surface Impoundments § 265.225 Waste analysis and trial tests. (a) In addition to the...

40 CFR 265.225 - Waste analysis and trial tests.

Code of Federal Regulations, 2012 CFR

2012-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Surface Impoundments § 265.225 Waste analysis and trial tests. (a) In addition to the...

40 CFR 265.225 - Waste analysis and trial tests.

Code of Federal Regulations, 2014 CFR

2014-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Surface Impoundments § 265.225 Waste analysis and trial tests. (a) In addition to the...

40 CFR 265.200 - Waste analysis and trial tests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... operator to place the results from each waste analysis and trial test, or the documented information, in... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Tank Systems § 265.200 Waste analysis and trial tests. In addition to performing the...

40 CFR 265.225 - Waste analysis and trial tests.

Code of Federal Regulations, 2011 CFR

2011-07-01

... waste analysis and trial test, or the documented information, in the operating record of the facility... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Surface Impoundments § 265.225 Waste analysis and trial tests. (a) In addition to the...

40 CFR 265.200 - Waste analysis and trial tests.

Code of Federal Regulations, 2011 CFR

2011-07-01

... operator to place the results from each waste analysis and trial test, or the documented information, in... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Tank Systems § 265.200 Waste analysis and trial tests. In addition to performing the...

40 CFR 265.200 - Waste analysis and trial tests.

Code of Federal Regulations, 2012 CFR

2012-07-01

... operator to place the results from each waste analysis and trial test, or the documented information, in... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Tank Systems § 265.200 Waste analysis and trial tests. In addition to performing the...

40 CFR 265.200 - Waste analysis and trial tests.

Code of Federal Regulations, 2014 CFR

2014-07-01

... operator to place the results from each waste analysis and trial test, or the documented information, in... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Waste analysis and trial tests. 265... DISPOSAL FACILITIES Tank Systems § 265.200 Waste analysis and trial tests. In addition to performing the...

A centralized informatics infrastructure for the National Institute on Drug Abuse Clinical Trials Network.

PubMed

Pan, Jeng-Jong; Nahm, Meredith; Wakim, Paul; Cushing, Carol; Poole, Lori; Tai, Betty; Pieper, Carl F

2009-02-01

Clinical trial networks (CTNs) were created to provide a sustaining infrastructure for the conduct of multisite clinical trials. As such, they must withstand changes in membership. Centralization of infrastructure including knowledge management, portfolio management, information management, process automation, work policies, and procedures in clinical research networks facilitates consistency and ultimately research. In 2005, the National Institute on Drug Abuse (NIDA) CTN transitioned from a distributed data management model to a centralized informatics infrastructure to support the network's trial activities and administration. We describe the centralized informatics infrastructure and discuss our challenges to inform others considering such an endeavor. During the migration of a clinical trial network from a decentralized to a centralized data center model, descriptive data were captured and are presented here to assess the impact of centralization. We present the framework for the informatics infrastructure and evaluative metrics. The network has decreased the time from last patient-last visit to database lock from an average of 7.6 months to 2.8 months. The average database error rate decreased from 0.8% to 0.2%, with a corresponding decrease in the interquartile range from 0.04%-1.0% before centralization to 0.01-0.27% after centralization. Centralization has provided the CTN with integrated trial status reporting and the first standards-based public data share. A preliminary cost-benefit analysis showed a 50% reduction in data management cost per study participant over the life of a trial. A single clinical trial network comprising addiction researchers and community treatment programs was assessed. The findings may not be applicable to other research settings. The identified informatics components provide the information and infrastructure needed for our clinical trial network. Post centralization data management operations are more efficient and less costly, with higher data quality.

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti‐neutrophil cytoplasm antibody‐associated vasculitis

PubMed Central

Hellmich, Bernhard; Flossmann, Oliver; Gross, Wolfgang L; Bacon, Paul; Cohen‐Tervaert, Jan Willem; Guillevin, Loic; Jayne, David; Mahr, Alfred; Merkel, Peter A; Raspe, Heiner; Scott, David G I; Witter, James; Yazici, Hasan; Luqmani, Raashid A

2007-01-01

Objectives To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. Methods An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence‐based and expert opinion‐based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. Results Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti‐neutrophil cytoplasm antibody‐associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis‐specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. Conclusions On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well‐designed research in non‐AAV systemic vasculitides. PMID:17170053

Recruiting to a large-scale physical activity randomised controlled trial - experiences with the gift of hindsight.

PubMed

Copeland, Robert J; Horspool, Kimberley; Humphreys, Liam; Scott, Emma

2016-02-24

Recruitment issues continue to impact a large number of trials. Sharing recruitment information is vital to supporting researchers to accurately predict recruitment and to manage the risk of poor recruitment during study design and implementation. The purpose of this article is to build on the knowledge available to researchers on recruiting to community-based trials. A critical commentary of the recruitment challenges encountered during the Booster Study, a randomised controlled trial in which researchers investigated the effectiveness of a motivational interviewing style intervention on the maintenance of physical activity. An overview of recruitment is provided, as well as strategies employed to recruit prospective participants and possible barriers to recruitment. Two hundred eighty-two people, 47 % of the original target, were recruited through mail-outs, with secondary recruitment pathways yielding no additional participants. The research team encountered problems with recontacting interested participants and providing study materials in non-English languages. A lower response rate to the mail-out and a greater number of non-contactable participants in the full study than in the pilot study resulted in a smaller pool of eligible participants from the brief intervention eligible for recruitment into the randomised controlled trial. Despite using widely accepted recruitment strategies and incorporating new recruitment tactics in response to challenges, the Booster Study investigators failed to randomise a sufficient number of participants. Recruitment in trials of community-based behavioural interventions may have different challenges than trials based on clinical or primary care pathways. Specific challenges posed by the complexity of the study design and problems with staffing and resources were exacerbated by the need to revise upwards the number of mailed invitations as a result of the pilot study. Researchers should ensure study design facilitates recruitment and consider the implications of changing recruitment on the operational aspects of the trial. Where possible, the impact of new strategies should be measured, and recruitment successes and challenges should be shared with those planning similar studies. ISRCTN56495859 (registered on 12 February 2009); NCT00836459 (registered on 3 February 2009).

Graded activity for low back pain in occupational health care: a randomized, controlled trial.

PubMed

Staal, J Bart; Hlobil, Hynek; Twisk, Jos W R; Smid, Tjabe; Köke, Albère J A; van Mechelen, Willem

2004-01-20

Low back pain is a common medical and social problem frequently associated with disability and absence from work. However, data on effective return to work after interventions for low back pain are scarce. To determine the effectiveness of a behavior-oriented graded activity program compared with usual care. Randomized, controlled trial. Occupational health services department of an airline company in the Netherlands. 134 workers who were absent from work because of low back pain were randomly assigned to either graded activity (n = 67) or usual care (n = 67). Graded activity, a physical exercise program based on operant-conditioning behavioral principles, to stimulate a rapid return to work. Outcomes were the number of days of absence from work because of low back pain, functional status (Roland Disability Questionnaire), and severity of pain (11-point numerical scale). The median number of days of absence from work over 6 months of follow-up was 58 days in the graded activity group and 87 days in the usual care group. From randomization onward, graded activity was effective after 50 days of absence from work (hazard ratio, 1.9 [95% CI, 1.2 to 3.2]; P = 0.009). The graded activity group was more effective in improving functional status and pain than the usual care group. The effects, however, were small and not statistically significant. Graded activity was more effective than usual care in reducing the number of days of absence from work because of low back pain.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

PubMed

Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

2015-05-01

A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The Endurance of Children's Working Memory: A Recall Time Analysis

ERIC Educational Resources Information Center

Towse, John N.; Hitch, Graham J.; Hamilton, Z.; Pirrie, Sarah

2008-01-01

We analyze the timing of recall as a source of information about children's performance in complex working memory tasks. A group of 8-year-olds performed a traditional operation span task in which sequence length increased across trials and an operation period task in which processing requirements were extended across trials of constant sequence…

Reforms speed initiation of NCI-sponsored clinical trials

Cancer.gov

The process of opening a cancer clinical trial for patient accrual often takes years, and research has shown that trials which are slow to register patients often fail to finish. Following a thorough review, NCI’s Operational Efficiency Working Group prod

Ear Acupuncture for Post-Operative Pain Associated with Ambulatory Arthroscopic Knee Surgery: A Randomized Controlled Trial

DTIC Science & Technology

2014-01-14

E7(/(3+21(180%(5 ,QFOXGHDUHDFRGH 14 Jan 2014 Final Report Ear acupuncture for post-operative pain associated with ambulatory arthroscopic...DISTRIBUTION A. Approved for public release: distribution unlimited. The purpose of this study is to compare ear acupuncture plus standard therapy versus...3298 Ear Acupuncture for Post-operative Pa111 Assoc1ated With Ambulatory Arthroscopic Knee Surgery A Randomized Controlled Trial ’• V ’’ ’-’ I

AAtS over AeroMACS Technology Trials on the Airport Surface

NASA Technical Reports Server (NTRS)

Apaza, Rafael; Abraham, Biruk; Maeda, Toshihide

2016-01-01

Air-Ground component of SWIM; Enables enhanced two-way information exchanges between flight operators, aircrew, and ATSP (TFM); Used in all flight domains including pre-departure and post-arrival; Aircrew active in CDM; For strategic planning, advisory information; Not for command control (data voice) Wireless communications system for airport surface; Family member of Mobile WiMAX: (IEEE802.16e), Band 5091-5150 MHz, Bandwidth 5 MHz - TDDOFDMA - Adaptive Modulation and Coding - Quality of Service (QoS)

Central endoscopy reads in inflammatory bowel disease clinical trials: The role of the imaging core lab

PubMed Central

Ahmad, Harris; Berzin, Tyler M.; Yu, Hui Jing; Huang, Christopher S.; Mishkin, Daniel S.

2014-01-01

Clinical trials in inflammatory bowel disease (IBD) are evolving at a rapid pace by employing central reading for endoscopic mucosal assessment in a field that was, historically, largely based on assessments by local physicians. This transition from local to central reading carries with it numerous technical, operational, and scientific challenges, many of which can be resolved by imaging core laboratories (ICLs), a concept that has a longer history in clinical trials in a number of diseases outside the realm of gastroenterology. For IBD trials, ICLs have the dual goals of providing objective, consistent assessments of endoscopic findings using central-reading paradigms whilst providing important expertise with regard to operational issues and regulatory expectations. This review focuses on current approaches to using ICLs for central endoscopic reading in IBD trials. PMID:24994835

How many research nurses for how many clinical trials in an oncology setting? Definition of the Nursing Time Required by Clinical Trial-Assessment Tool (NTRCT-AT).

PubMed

Milani, Alessandra; Mazzocco, Ketti; Stucchi, Sara; Magon, Giorgio; Pravettoni, Gabriella; Passoni, Claudia; Ciccarelli, Chiara; Tonali, Alessandra; Profeta, Teresa; Saiani, Luisa

2017-02-01

Few resources are available to quantify clinical trial-associated workload, needed to guide staffing and budgetary planning. The aim of the study is to describe a tool to measure clinical trials nurses' workload expressed in time spent to complete core activities. Clinical trials nurses drew up a list of nursing core activities, integrating results from literature searches with personal experience. The final 30 core activities were timed for each research nurse by an outside observer during daily practice in May and June 2014. Average times spent by nurses for each activity were calculated. The "Nursing Time Required by Clinical Trial-Assessment Tool" was created as an electronic sheet that combines the average times per specified activities and mathematic functions to return the total estimated time required by a research nurse for each specific trial. The tool was tested retrospectively on 141 clinical trials. The increasing complexity of clinical research requires structured approaches to determine workforce requirements. This study provides a tool to describe the activities of a clinical trials nurse and to estimate the associated time required to deliver individual trials. The application of the proposed tool in clinical research practice could provide a consistent structure for clinical trials nursing workload estimation internationally. © 2016 John Wiley & Sons Australia, Ltd.

Community Agency Survey Formative Research Results From the TAAG Study

PubMed Central

Saunders, Ruth P.; Moody, Jamie

2008-01-01

School and community agency collaboration can potentially increase physical activity opportunities for youth. Few studies have examined the role of community agencies in promoting physical activity, much less in collaboration with schools. This article describes formative research data collection from community agencies to inform the development of the Trial of Activity for Adolescent Girls (TAAG) intervention to provide out-of-school physical activity programs for girls. The community agency survey is designed to assess agency capacity to provide physical activity programs for girls, including resources, programs, and partnerships. Most agency respondents (n = 138) report operations during after-school hours, adequate facilities, and program options for girls, although most are sport oriented. Agency resources and programming vary considerably across the six TAAG field sites. Many agencies report partnerships, some involving schools, although not necessarily related to physical activity. Implications for the TAAG intervention are presented. PMID:16397156

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

PubMed

Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

2017-07-01

Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological active placebo control interventions are rarely used in randomized clinical trials, but they constitute a methodological tool which merits serious consideration. We suggest that active placebos are used more often in trials of drugs with noticeable side effects, especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high. Copyright © 2017 Elsevier Inc. All rights reserved.

Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer.

PubMed

Bauman, Julie E; Duvvuri, Umamaheswar; Gooding, William E; Rath, Tanya J; Gross, Neil D; Song, John; Jimeno, Antonio; Yarbrough, Wendell G; Johnson, Faye M; Wang, Lin; Chiosea, Simion; Sen, Malabika; Kass, Jason; Johnson, Jonas T; Ferris, Robert L; Kim, Seungwon; Hirsch, Fred R; Ellison, Kimberly; Flaherty, John T; Mills, Gordon B; Grandis, Jennifer R

2017-03-23

BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II-IVa HNSCC were randomized to 7-21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo. Paired tumor specimens were collected before and after treatment. Pharmacodynamic expression of EGFR and Src pathway components was evaluated by IHC of tissue microarrays and reverse-phase protein array of tissue lysates. Candidate biomarkers were assessed for correlation with change in tumor size. RESULTS. From April 2009 to December 2012, 58 patients were randomized and 55 were treated. There was a significant decrease in tumor size in both erlotinib arms ( P = 0.0014); however, no effect was seen with dasatinib alone ( P = 0.24). High baseline pMAPK expression was associated with response to erlotinib ( P = 0.03). High baseline pSTAT3 was associated with resistance to dasatinib ( P = 0.099). CONCLUSIONS. Brief exposure to erlotinib significantly decreased tumor size in operable HNSCC, with no additive effect from dasatinib. Baseline pMAPK expression warrants further study as a response biomarker for anti-EGFR therapy. Basal expression of pSTAT3 may be independent of Src, explain therapeutic resistance, and preclude development of dasatinib in biomarker-unselected cohorts. TRIAL REGISTRATION. NCT00779389. FUNDING. National Cancer Institute, American Cancer Society, Pennsylvania Department of Health, V Foundation for Cancer Research, Bristol-Myers Squibb, and Astellas Pharma.

Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer

PubMed Central

Bauman, Julie E.; Duvvuri, Umamaheswar; Gooding, William E.; Rath, Tanya J.; Gross, Neil D.; Song, John; Jimeno, Antonio; Yarbrough, Wendell G.; Johnson, Faye M.; Wang, Lin; Chiosea, Simion; Sen, Malabika; Kass, Jason; Johnson, Jonas T.; Ferris, Robert L.; Kim, Seungwon; Hirsch, Fred R.; Ellison, Kimberly; Flaherty, John T.; Mills, Gordon B.

2017-01-01

BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II–IVa HNSCC were randomized to 7–21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo. Paired tumor specimens were collected before and after treatment. Pharmacodynamic expression of EGFR and Src pathway components was evaluated by IHC of tissue microarrays and reverse-phase protein array of tissue lysates. Candidate biomarkers were assessed for correlation with change in tumor size. RESULTS. From April 2009 to December 2012, 58 patients were randomized and 55 were treated. There was a significant decrease in tumor size in both erlotinib arms (P = 0.0014); however, no effect was seen with dasatinib alone (P = 0.24). High baseline pMAPK expression was associated with response to erlotinib (P = 0.03). High baseline pSTAT3 was associated with resistance to dasatinib (P = 0.099). CONCLUSIONS. Brief exposure to erlotinib significantly decreased tumor size in operable HNSCC, with no additive effect from dasatinib. Baseline pMAPK expression warrants further study as a response biomarker for anti-EGFR therapy. Basal expression of pSTAT3 may be independent of Src, explain therapeutic resistance, and preclude development of dasatinib in biomarker-unselected cohorts. TRIAL REGISTRATION. NCT00779389. FUNDING. National Cancer Institute, American Cancer Society, Pennsylvania Department of Health, V Foundation for Cancer Research, Bristol-Myers Squibb, and Astellas Pharma. PMID:28352657

Supplemental Peri-Operative Oxygen and Incision Site Infection after Surgery for Perforated Peptic Ulcer: A Randomized, Double-Blind Monocentric Trial.

PubMed

Schietroma, Mario; Cecilia, Emanuela Marina; De Santis, Giuseppe; Carlei, Francesco; Pessia, Beatrice; Amicucci, Gianfranco

2016-02-01

The clinical role of hyperoxia for preventing surgical site infection (SSI) remains uncertain because randomized controlled trials on this topic have reported disparate results. One of the principal reasons for this outcome may be that prior trials have entered heterogeneous populations of patients and a variety of procedures. The aim of our study was to assess the influence of hyperoxygenation on SSI using a homogeneous study population. From January 2004 to April 2013, we studied, in a randomized trial, 239 patients, who underwent open surgery for perforated peptic ulcer (PPU). The surgical procedure was performed through an upper abdominal midline incision, and closure of PPU was achieved by suture alone or in combination with an omental patch. Patients were assigned randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of 30% (n = 120) or 80% (n = 119). Administration was commenced after induction of anesthesia and maintained for 6 hours after surgery. The overall incision infection rate was 38.4% (92 of 239): 61 patients (50.8%) had an infection in the 30% FiO2 group and 31 (26%) in the 80% FiO2 group (p < 0.05). The risk of SSI was 48% lower in the 80% FiO2 group (relative risk 0.51; 95% confidence interval [CI] 0.28-1.08) vs 30% FiO2. Supplemental 80% FiO2 during and for 6 h after open surgery for PPU, which reduces post-operative SSI, should be considered part of ongoing quality improvement activities related to surgical care, with few risks to the patient and little associated cost.

Early response to therapy predicts 6-month and 1-year disease activity outcomes in psoriatic arthritis patients.

PubMed

Schoels, Monika M; Landesmann, Uriel; Alasti, Farideh; Baker, Daniel; Smolen, Josef S; Aletaha, Daniel

2018-06-01

In PsA management, remission and low disease activity represent preferential treatment targets. We aimed at evaluating the predictive value and clinical use of initial therapeutic response for subsequent achievement of these targets. Based on data of 216 patients enrolled in a randomized controlled trial of golimumab (GO-REVEAL), we performed diagnostic testing analyses using 3- and 6-month disease activity as tests for treatment outcomes to understand the implications of early response. In regression analyses, we estimated the probabilities for achieving at least LDA. Disease activity was measured by the disease activity index for PsA (DAPSA). Three-month DAPSA levels were excellent tests for disease activity at 6 months (and at 1 year), with areas under the receiver operating characteristic curves of 0.92 (and 0.88, respectively). The estimated probability for 6-month LDA could be quantified as <22% if patients did not reach at least moderate disease activity after 3 months on golimumab. Similar data were seen for early DAPSA response: patients achieving a DAPSA 85% at 3 months had an 84% probability for 6-month LDA or REM. All results were validated in an independent trial cohort of patients treated with infliximab (IMPACT 2). Three months after implementation of therapy in PsA, it is already possible to evaluate the potential for accomplishing therapeutic goals. This substantiates the choice of the 3-month assessment as essential for treatment adaptations.

The effect of concentrated bone marrow aspirate in operative treatment of fifth metatarsal stress fractures; a double-blind randomized controlled trial.

PubMed

Weel, Hanneke; Mallee, Wouter H; van Dijk, C Niek; Blankevoort, Leendert; Goedegebuure, Simon; Goslings, J Carel; Kennedy, John G; Kerkhoffs, Gino M M J

2015-08-20

Fifth metatarsal (MT-V) stress fractures often exhibit delayed union and are high-risk fractures for non-union. Surgical treatment, currently considered as the gold standard, does not give optimal results, with a mean time to fracture union of 12-18 weeks. In recent studies, the use of bone marrow cells has been introduced to accelerate healing of fractures with union problems. The aim of this randomized trial is to determine if operative treatment of MT-V stress fractures with use of concentrated blood and bone marrow aspirate (cB + cBMA) is more effective than surgery alone. We hypothesize that using cB + cBMA in the operative treatment of MT-V stress fractures will lead to an earlier fracture union. A prospective, double-blind, randomized controlled trial (RCT) will be conducted in an academic medical center in the Netherlands. Ethics approval is received. 50 patients will be randomized to either operative treatment with cB + cBMA, harvested from the iliac crest, or operative treatment without cB + cBMA but with a sham-treatment of the iliac crest. The fracture fixation is the same in both groups, as is the post-operative care.. Follow up will be one year. The primary outcome measure is time to union in weeks on X-ray. Secondary outcome measures are time to resumption of work and sports, functional outcomes (SF-36, FAOS, FAAM), complication rate, composition of osteoprogenitors in cB + cBMA and cost-effectiveness. Furthermore, a bone biopsy is taken from every stress fracture and analysed histologically to determine the stage of the stress fracture. The difference in primary endpoint between the two groups is analysed using student's t-test or equivalent. This trial will likely provide level-I evidence on the effectiveness of cB + cBMA in the operative treatment of MT-V stress fractures. Netherlands Trial Register (reg.nr NTR4377 ).

Are large clinical trials in orthopaedic trauma justified?

PubMed

Sprague, Sheila; Tornetta, Paul; Slobogean, Gerard P; O'Hara, Nathan N; McKay, Paula; Petrisor, Brad; Jeray, Kyle J; Schemitsch, Emil H; Sanders, David; Bhandari, Mohit

2018-04-20

The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008.

Networking health research in Britain: the post-war childhood leukaemia trials.

PubMed

Moscucci, Ornella; Herring, Rachel; Berridge, Virginia

2009-01-01

The treatment of childhood leukaemia is seen as a successful historical example of the operation of the randomized controlled trial and continues to inform contemporary policy making on such trials within health research. This article analyses the scientists' 'story of success' through historical research. It tells us about the organizational and professional structures of such research post-war in the United Kingdom, and examines the history of the cancer clinical trial through this particular example. The story reveals a more complex picture than the 'heroic' one, with key developments in the operation of post-war science, both in terms of its infrastructure and of its scientific networks, not least the rise of co-operative working among clinicians and the growing importance of statisticians in medical research and practice. It also underlines differences between the British and US approaches in which the role of one health system, the National Health Service, helped structure different, initially less intensive, patterns of response.

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.

Clinical trials finance and operations.

PubMed

O'Brien, Jennifer A

2007-01-01

The National Coverage Decision of 2000 was designed to enhance the participation in clinical trials for both patients and physicians by mandating the governmental coverage for services in a clinical trial that are considered "routine" regardless of the trial. Participation in clinical trials can be a practice builder as well as a contribution to the betterment of medical science. Without proper coverage analysis, study budgeting, accurate time estimates, and effective negotiation prior to signing the contract, participation in clinical trials can cost a practice rather than benefit it.

Canadian aeronautical mobile data trials

NASA Technical Reports Server (NTRS)

Pedersen, Allister; Pearson, Andrea

1993-01-01

This paper describes a series of aeronautical mobile data trials conducted on small aircraft (helicopters and fixed wing) utilizing a low-speed store-and-forward mobile data service. The paper outlines the user requirements for aeronautical mobile satellite communications. 'Flight following' and improved wide-area dispatch communications were identified as high priority requirements. A 'proof-of-concept' trial in a Cessna Skymaster aircraft is described. This trial identified certain development work as essential to the introduction of commercial service including antenna development, power supply modifications and doppler software modifications. Other improvements were also proposed. The initial aeronautical mobile data service available for pre-operational (Beta) trials is outlined. Pre-operational field trials commenced in October 1992 and consisted of installations on a Gralen Communications Inc. Cessna 177 and an Aerospatiale Astar 350 series light single engine helicopter. The paper concludes with a discussion of desirable near term mobile data service developments, commercial benefits, current safety benefits and potential future applications for improved safety.

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the design and operation of multi-center clinical trials: a qualitative research study.

PubMed

Eisenstein, Eric L; Diener, Lawrence W; Nahm, Meredith; Weinfurt, Kevin P

2011-12-01

New technologies may be required to integrate the National Institutes of Health's Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies.

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the Design and Operation of Multi-center Clinical Trials: a Qualitative Research Study

PubMed Central

Diener, Lawrence W.; Nahm, Meredith; Weinfurt, Kevin P.

2013-01-01

New technologies may be required to integrate the National Institutes of Health’s Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies. PMID:20703765

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

2017-08-05

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2017) and reference lists of retrieved studies. All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. We assessed methodological quality of the one included trial using the GRADE approach. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. The trial compared the antibiotic intravenous cefotetan after cord clamping compared with no treatment. This trial reported only two out of the nine outcomes specified in this review. Seven women in the group given no antibiotics had endomyometritis and none in prophylactic antibiotic group, the risk reduction was 93% (risk ratio (RR) 0.07; 95% confidence interval (CI) 0.00 to 1.21; low-quality evidence). There was no difference in the length of hospital stay between the two groups (mean difference (MD) 0.09 days; 95% CI -0.23 to 0.41; low-quality evidence). Overall, the risk of bias was judged to be unclear. The quality of the evidence using GRADE was low for both endometritis and maternal length of stay. One small trial was identified reporting only two outcomes. Evidence from this single trial suggests that antibiotic prophylaxis may lead to little or no difference in endometritis or maternal length of stay. There were no data on any other outcomes to evaluate the impact of antibiotic prophylaxis after operative vaginal delivery. Future research on antibiotic prophylaxis for operative vaginal delivery is needed to conclude whether it is useful for reducing postpartum morbidity.

Qualitative analysis of ultra-short optical dissipative solitary pulses in the actively mode-locked semiconductor heterolasers with an external fiber cavity

NASA Astrophysics Data System (ADS)

Shcherbakov, Alexandre S.; Campos Acosta, Joaquin; Moreno Zarate, Pedro; Pons Aglio, Alicia

2011-02-01

An advanced qualitative characterization of simultaneously existing various low-power trains of ultra-short optical pulses with an internal frequency modulation in a distributed laser system based on semiconductor heterostructure is presented. The scheme represents a hybrid cavity consisting of a single-mode heterolaser operating in the active mode-locking regime and an external long single-mode optical fiber exhibiting square-law dispersion, cubic Kerr nonlinearity, and linear optical losses. In fact, we consider the trains of optical dissipative solitons, which appear within double balance between the second-order dispersion and cubic-law nonlinearity as well as between the active-medium gain and linear optical losses in a hybrid cavity. Moreover, we operate on specially designed modulating signals providing non-conventional composite regimes of simultaneous multi-pulse active mode-locking. As a result, the mode-locking process allows shaping regular trains of picosecond optical pulses excited by multi-pulse independent on each other sequences of periodic modulations. In so doing, we consider the arranged hybrid cavity as a combination of a quasi-linear part responsible for the active mode-locking by itself and a nonlinear part determining the regime of dissipative soliton propagation. Initially, these parts are analyzed individually, and then the primarily obtained data are coordinated with each other. Within this approach, a contribution of the appeared cubically nonlinear Ginzburg-Landau operator is analyzed via exploiting an approximate variational procedure involving the technique of trial functions.

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

PubMed

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

2017-09-07

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

The feasibility and acceptability of trial procedures for a pragmatic randomised controlled trial of a structured physical activity intervention for people diagnosed with colorectal cancer: findings from a pilot trial of cardiac rehabilitation versus usual care (no rehabilitation) with an embedded qualitative study.

PubMed

Hubbard, Gill; O'Carroll, Ronan; Munro, Julie; Mutrie, Nanette; Haw, Sally; Mason, Helen; Treweek, Shaun

2016-01-01

Pilot and feasibility work is conducted to evaluate the operational feasibility and acceptability of the intervention itself and the feasibility and acceptability of a trials' protocol design. The Cardiac Rehabilitation In Bowel cancer (CRIB) study was a pilot randomised controlled trial (RCT) of cardiac rehabilitation versus usual care (no rehabilitation) for post-surgical colorectal cancer patients. A key aim of the pilot trial was to test the feasibility and acceptability of the protocol design. A pilot RCT with embedded qualitative work was conducted in three sites. Participants were randomly allocated to cardiac rehabilitation or usual care groups. Outcomes used to assess the feasibility and acceptability of key trial parameters were screening, eligibility, consent, randomisation, adverse events, retention, completion, missing data, and intervention adherence rates. Colorectal patients' and clinicians' perceptions and experiences of the main trial procedures were explored by interview. Quantitative study. Three sites were involved. Screening, eligibility, consent, and retention rates were 79 % (156/198), 67 % (133/198), 31 % (41/133), and 93 % (38/41), respectively. Questionnaire completion rates were 97.5 % (40/41), 75 % (31/41), and 61 % (25/41) at baseline, follow-up 1, and follow-up 2, respectively. Sixty-nine percent (40) of accelerometer datasets were collected from participants; 31 % (20) were removed for not meeting wear-time validation. Qualitative study: Thirty-eight patients and eight clinicians participated. Key themes were benefits for people with colorectal cancer attending cardiac rehabilitation, barriers for people with colorectal cancer attending cardiac rehabilitation, generic versus disease-specific rehabilitation, key concerns about including people with cancer in cardiac rehabilitation, and barriers to involvement in a study about cardiac rehabilitation. The study highlights where threats to internal and external validity are likely to arise in any future studies of similar structured physical activity interventions for colorectal cancer patients using similar methods being conducted in similar contexts. This study shows that there is likely to be potential recruitment bias and potential imprecision due to sub-optimal completion of outcome measures, missing data, and sub-optimal intervention adherence. Hence, strategies to manage these risks should be developed to stack the odds in favour of conducting successful future trials. ISRCTN63510637.

A randomised controlled trial to determine the clinical and cost effectiveness of thulium laser transurethral vaporesection of the prostate (ThuVARP) versus transurethral resection of the prostate (TURP) in the National Health Service (NHS) - the UNBLOCS trial: a study protocol for a randomised controlled trial.

PubMed

Worthington, Jo; Taylor, Hilary; Abrams, Paul; Brookes, Sara T; Cotterill, Nikki; Noble, Sian M; Page, Tobias; Swami, K Satchi; Lane, J Athene; Hashim, Hashim

2017-04-17

Transurethral resection of the prostate (TURP) has been the standard operation for benign prostatic obstruction (BPO) for 40 years, with approximately 25,000 procedures performed annually, and has remained largely unchanged. It is generally a successful operation, but has well-documented risks for the patient. Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a surgical technique similar to TURP. The small amount of study data currently available suggests that ThuVARP may have certain advantages over TURP, including reduced blood loss and shorter hospital stay, earlier return to normal activities, and shorter duration of catheterisation. A multicentre, pragmatic, randomised, controlled, parallel-group trial of ThuVARP versus standard TURP in men with BPO. Four hundred and ten men suitable for prostate surgery were randomised to receive either ThuVARP or TURP at four university teaching hospitals, and three district general hospitals. The key aim of the trial is to determine whether ThuVARP is equivalent to TURP judged on both the patient-reported International Prostate Symptom Score (IPSS) and the maximum urine flow rate (Qmax) at 12 months post-surgery. The general population has an increased life expectancy. As men get older their prostates enlarge, potentially causing BPO, which often requires surgery. Therefore, as the population ages, more prostate operations are needed to relieve obstruction. There is hence sustained interest in the condition and increasing need to find safer techniques than TURP. Various laser techniques have become available but none are widely used in the NHS because of lengthy training required for surgeons or inferior performance on clinical outcomes. Promising initial evidence from one RCT shows that ThuVARP has equivalent clinical effectiveness when compared to TURP, as well as other potential advantages. As ThuVARP uses a technique similar to that used in TURP, the learning curve is short, potentially making it also very quickly generalisable. This randomised study is designed to provide the high-quality evidence, in an NHS setting, with a range of patient-reported, clinical and cost-effectiveness outcomes, which will underpin and inform future NICE guidance. ISRCTN registry, ISRCTN00788389 . Registered on 20 September 2013.

Impact of the new european paediatric regulatory framework on ethics committees: overview and perspectives.

PubMed

Altavilla, A; Manfredi, C; Baiardi, P; Dehlinger-Kremer, M; Galletti, P; Pozuelo, A Alemany; Chaplin, J; Ceci, A

2012-01-01

To evaluate the impact of the new European paediatric regulatory framework on the activities of Ethics Committees operating in Europe and to assess their involvement and interest in paediatric research. Task-force in Europe for Drug Development for the Young Network of Excellence and Relating Expectations and Needs to the Participation and Empowerment of Children in Clinical Trials project set up an inventory of Ethics Committees existing in Europe and conducted a survey on their approach to paediatric trials. Ethics Committees operating in 22 European Countries participated in this survey. Results showed a high lack of knowledge, understanding and awareness of the current European paediatric regulatory framework and a lack of involvement of Ethics Committees in paediatric research, especially in terms of training and education, demonstrated also by the decreasing number of Ethics Committees answering exhaustively to the whole questionnaire. The majority of participating Ethics Committees expressed interest in future initiatives related to paediatric research. Despite a limited knowledge and understanding of the current paediatric regulatory framework, a significant number of Ethics Committees operating in Europe show interest in initiatives related to paediatric research. Networking may be an essential tool to be used to enhance Ethics Committees role in supporting paediatric research. Any initiative should be undertaken at European level in collaboration with European Union Institutions. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

Operational Evaluatioin of Dynamic Weather Routes at American Airlines

NASA Technical Reports Server (NTRS)

McNally, David; Sheth, Kapil; Gong, Chester; Borchers, Paul; Osborne, Jeff; Keany, Desmond; Scott, Brennan; Smith, Steve; Sahlman, Scott; Lee, Chuhan;

Evaluation of the clinical benefit of an electromagnetic navigation system for CT-guided interventional radiology procedures in the thoraco-abdominal region compared with conventional CT guidance (CTNAV II): study protocol for a randomised controlled trial.

PubMed

Rouchy, R C; Moreau-Gaudry, A; Chipon, E; Aubry, S; Pazart, L; Lapuyade, B; Durand, M; Hajjam, M; Pottier, S; Renard, B; Logier, R; Orry, X; Cherifi, A; Quehen, E; Kervio, G; Favelle, O; Patat, F; De Kerviler, E; Hughes, C; Medici, M; Ghelfi, J; Mounier, A; Bricault, I

2017-07-06

Interventional radiology includes a range of minimally invasive image-guided diagnostic and therapeutic procedures that have become routine clinical practice. Each procedure involves a percutaneous needle insertion, often guided using computed tomography (CT) because of its availability and usability. However, procedures remain complicated, in particular when an obstacle must be avoided, meaning that an oblique trajectory is required. Navigation systems track the operator's instruments, meaning the position and progression of the instruments are visualised in real time on the patient's images. A novel electromagnetic navigation system for CT-guided interventional procedures (IMACTIS-CT®) has been developed, and a previous clinical trial demonstrated improved needle placement accuracy in navigation-assisted procedures. In the present trial, we are evaluating the clinical benefit of the navigation system during the needle insertion step of CT-guided procedures in the thoraco-abdominal region. This study is designed as an open, multicentre, prospective, randomised, controlled interventional clinical trial and is structured as a standard two-arm, parallel-design, individually randomised trial. A maximum of 500 patients will be enrolled. In the experimental arm (navigation system), the procedures are carried out using navigation assistance, and in the active comparator arm (CT), the procedures are carried out with conventional CT guidance. The randomisation is stratified by centre and by the expected difficulty of the procedure. The primary outcome of the trial is a combined criterion to assess the safety (number of serious adverse events), efficacy (number of targets reached) and performance (number of control scans acquired) of navigation-assisted, CT-guided procedures as evaluated by a blinded radiologist and confirmed by an expert committee in case of discordance. The secondary outcomes are (1) the duration of the procedure, (2) the satisfaction of the operator and (3) the irradiation dose delivered, with (4) subgroup analysis according to the expected difficulty of the procedure, as well as an evaluation of (5) the usability of the device. This trial addresses the lack of published high-level evidence studies in which navigation-assisted CT-guided interventional procedures are evaluated. This trial is important because it addresses the problems associated with conventional CT guidance and is particularly relevant because the number of interventional radiology procedures carried out in routine clinical practice is increasing. ClinicalTrials.gov identifier: NCT01896219 . Registered on 5 July 2013.

Modifying the clinical research infrastructure at a dedicated clinical trials unit: assessment of trial development, activation, and participant accrual

PubMed Central

Tang, Chad; Hess, Kenneth R.; Sanders, Dwana; Davis, Suzanne; Buzdar, Aman; Kurzrock, Razelle; Lee, J. Jack; Meric-Bernstam, Funda; Hong, David

2017-01-01

Purpose Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center and analyzed their effects on the trial activation timeline and enrollment. Experimental Design Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results We identified 3 facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship (industry [133 ICT and 133 non-ICT trials] or institutional [68 ICT and 68 non-ICT trials]). ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrollment (median difference of 0.3 months for industry vs. 1.2 months for institutional) (all matched P<0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional) (all matched P<0.05). Conclusions Use of a clinical research–focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. PMID:27852698

Modifying the Clinical Research Infrastructure at a Dedicated Clinical Trials Unit: Assessment of Trial Development, Activation, and Participant Accrual.

PubMed

Tang, Chad; Hess, Kenneth R; Sanders, Dwana; Davis, Suzanne E; Buzdar, Aman U; Kurzrock, Razelle; Lee, J Jack; Meric-Bernstam, Funda; Hong, David S

2017-03-15

Purpose: Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center (Houston, TX) and analyzed their effects on the trial activation timeline and enrolment. Experimental Design: Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database, we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results: We identified three facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship [industry (133 ICT and 133 non-ICT trials) or institutional (68 ICT and 68 non-ICT trials)]. ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrolment (median difference of 0.3 months for industry vs. 1.2 months for institutional; all matched P < 0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional; all matched P < 0.05). Conclusions: Use of a clinical research-focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. Clin Cancer Res; 23(6); 1407-13. ©2016 AACR . ©2016 American Association for Cancer Research.

Is consciousness necessary for conflict detection and conflict resolution?

PubMed

Xiang, Ling; Wang, Baoxi; Zhang, Qinglin

2013-06-15

Is conflict control dependent on consciousness? To answer this question, we used high temporal resolution event-related potentials (ERPs) to separate conflict detection from conflict resolution in a masked prime Stroop task. Although behavioral interference effect was present in both the masked and unmasked conditions, the electrophysiological findings revealed more complex patterns. ERP analyses showed that N450 was greater for incongruent trials than for congruent trials and that it was located in the ACC and nearby motor cortex, regardless of whether the primes were masked or unmasked; however, the effects were smaller for the masked than unmasked condition. These results suggest that consciousness of conflict information may not be necessary for detecting conflict, but that it may modulate conflict detection. The analysis of slow potential (SP) amplitude showed that it distinguished incongruent trials from congruent trials, and that this modulation effects was reduced to a greater extent for the masked condition than for the unmasked condition. Moreover, the prefrontal-parietal control network was activated under the unmasked but not under the masked condition. These results suggest that the consciousness of conflict information may be a necessary boundary condition for the subsequent initiation of control operations in the more extended PFC-parietal control network. However, considering that the conflict interference effect was significantly reduced in the masked condition, it may be that, with larger unconscious conflict effects, more extensive cognitive control networks would have been activated. These findings have important implications for theories on the relationship between consciousness and cognitive control. Copyright © 2013 Elsevier B.V. All rights reserved.

The GoodNEWS (Genes, Nutrition, Exercise, Wellness, and Spiritual Growth) Trial: a community-based participatory research (CBPR) trial with African-American church congregations for reducing cardiovascular disease risk factors--recruitment, measurement, and randomization.

PubMed

DeHaven, Mark J; Ramos-Roman, Maria A; Gimpel, Nora; Carson, JoAnn; DeLemos, James; Pickens, Sue; Simmons, Chris; Powell-Wiley, Tiffany; Banks-Richard, Kamakki; Shuval, Kerem; Duvahl, Julie; Duval, Julie; Tong, Liyue; Hsieh, Natalie; Lee, Jenny J

2011-09-01

Although cardiovascular diseases (CVD) are the leading cause of death among Americans, significant disparities persist in CVD prevalence, morbidity, and mortality based on race and ethnicity. However, few studies have examined risk factor reduction among the poor and ethnic minorities. Community-based participatory research (CBPR) study using a cluster randomized design--African-American church congregations are the units of randomization and individuals within the congregations are the units of analysis. Outcome variables include dietary change (Diet History Questionnaire), level of physical activity (7-Day Physical Activity Recall), lipoprotein levels, blood pressure, fasting glucose, and hemoglobin A1c. Eighteen (18) church congregations were randomized to either a health maintenance intervention or a control condition. Complete data were obtained on 392 African-American individuals, 18 to 70 years of age, predominantly employed women with more than a high school diploma. Treatment and intervention groups were similar at baseline on saturated fat intake, metabolic equivalent of tasks (METS) per day, and other risk factors for CVD. The GoodNEWS trial successfully recruited and evaluated CVD-related risk among African-American participants using a CBPR approach. Several logistical challenges resulted in extending the recruitment, preliminary training, and measurement periods. The challenges were overcome with the assistance of a local community consultant and a professional event planner. Our experience supports the need for incorporating non-traditional community-based staff into the design and operational plan of CBPR trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Central endoscopy reads in inflammatory bowel disease clinical trials: The role of the imaging core lab.

PubMed

Ahmad, Harris; Berzin, Tyler M; Yu, Hui Jing; Huang, Christopher S; Mishkin, Daniel S

2014-08-01

Clinical trials in inflammatory bowel disease (IBD) are evolving at a rapid pace by employing central reading for endoscopic mucosal assessment in a field that was, historically, largely based on assessments by local physicians. This transition from local to central reading carries with it numerous technical, operational, and scientific challenges, many of which can be resolved by imaging core laboratories (ICLs), a concept that has a longer history in clinical trials in a number of diseases outside the realm of gastroenterology. For IBD trials, ICLs have the dual goals of providing objective, consistent assessments of endoscopic findings using central-reading paradigms whilst providing important expertise with regard to operational issues and regulatory expectations. This review focuses on current approaches to using ICLs for central endoscopic reading in IBD trials. © The Author(s) 2014. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

PubMed

Healy, Donagh; Clarke-Moloney, Mary; Gaughan, Brendan; O'Daly, Siobhan; Hausenloy, Derek; Sharif, Faisal; Newell, John; O'Donnell, Martin; Grace, Pierce; Forbes, John F; Cullen, Walter; Kavanagh, Eamon; Burke, Paul; Cross, Simon; Dowdall, Joseph; McMonagle, Morgan; Fulton, Greg; Manning, Brian J; Kheirelseid, Elrasheid A H; Leahy, Austin; Moneley, Daragh; Naughton, Peter; Boyle, Emily; McHugh, Seamus; Madhaven, Prakash; O'Neill, Sean; Martin, Zenia; Courtney, Donal; Tubassam, Muhammed; Sultan, Sherif; McCartan, Damian; Medani, Mekki; Walsh, Stewart

2015-04-23

Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff. Four hundred major vascular surgery patients in five Irish vascular centres will be randomised (stratified for centre and procedure) to undergo RIPC or not immediately before surgery. RIPC will be induced using a blood pressure cuff with four cycles of 5 minutes of ischaemia followed by 5 minutes of reperfusion immediately before the start of operations. There is no sham intervention. Participants will undergo serum troponin measurements pre-operatively and 1, 2, and 3 days post-operatively. Participants will undergo 12-lead electrocardiograms pre-operatively and on the second post-operative day. Predefined complications within one year of surgery will be recorded. Patient and staff experiences will be explored using qualitative techniques. The primary outcome measure is the proportion of patients who develop elevated serum troponin levels in the first 3 days post-operatively. Secondary outcome measures include length of hospital and critical care stay, unplanned critical care admissions, death, myocardial infarction, stroke, mesenteric ischaemia and need for renal replacement therapy (within 30 days of surgery). RIPC is novel intervention with the potential to significantly improve perioperative outcomes. This trial will provide the first evaluation of RIPC's ability to reduce adverse clinical events following major vascular surgery. www.clinicaltrials.gov NCT02097186 Date Registered: 24 March 2014.

Independent academic Data Monitoring Committees for clinical trials in cardiovascular and cardiometabolic diseases.

PubMed

Filippatos, Gerasimos S; de Graeff, Pieter; Bax, Jeroen J; Borg, John-Joseph; Cleland, John G F; Dargie, Henry J; Flather, Marcus; Ford, Ian; Friede, Tim; Greenberg, Barry; Henon-Goburdhun, Cécile; Holcomb, Richard; Horst, Bradley; Lekakis, John; Mueller-Velten, Guenther; Papavassiliou, Athanasios G; Prasad, Krishna; Rosano, Giuseppe M C; Severin, Thomas; Sherman, Warren; Stough, Wendy Gattis; Swedberg, Karl; Tavazzi, Luigi; Tousoulis, Dimitris; Vardas, Panagiotis; Ruschitzka, Frank; Anker, Stefan D

2017-04-01

Data Monitoring Committees (DMCs) play a crucial role in the conducting of clinical trials to ensure the safety of study participants and to maintain a trial's scientific integrity. Generally accepted standards exist for DMC composition and operational conduct. However, some relevant issues are not specifically addressed in current guidance documents, resulting in uncertainties regarding optimal approaches for communication between the DMC, steering committee, and sponsors, release of information, and liability protection for DMC members. The Heart Failure Association (HFA) of the European Society of Cardiology (ESC), in collaboration with the Clinical Trials Unit of the European Heart Agency (EHA) of the ESC convened a meeting of international experts in DMCs for cardiovascular and cardiometabolic clinical trials to identify specific issues and develop steps to resolve challenges faced by DMCs.The main recommendations from the meeting relate to methodological consistency, independence, managing conflicts of interest, liability protection, and training of future DMC members. This paper summarizes the key outcomes from this expert meeting, and describes the core set of activities that might be further developed and ultimately implemented by the ESC, HFA, and other interested ESC constituent bodies. The HFA will continue to work with stakeholders in cardiovascular and cardiometabolic clinical research to promote these goals. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Biases encountered in long-term monitoring studies of invertebrates and microflora: Australian examples of protocols, personnel, tools and site location.

PubMed

Greenslade, Penelope; Florentine, Singarayer K; Hansen, Brigita D; Gell, Peter A

2016-08-01

Monitoring forms the basis for understanding ecological change. It relies on repeatability of methods to ensure detected changes accurately reflect the effect of environmental drivers. However, operator bias can influence the repeatability of field and laboratory work. We tested this for invertebrates and diatoms in three trials: (1) two operators swept invertebrates from heath vegetation, (2) four operators picked invertebrates from pyrethrum knockdown samples from tree trunk and (3) diatom identifications by eight operators in three laboratories. In each trial, operators were working simultaneously and their training in the field and laboratory was identical. No variation in catch efficiency was found between the two operators of differing experience using a random number of net sweeps to catch invertebrates when sequence, location and size of sweeps were random. Number of individuals and higher taxa collected by four operators from tree trunks varied significantly between operators and with their 'experience ranking'. Diatom identifications made by eight operators were clustered together according to which of three laboratories they belonged. These three tests demonstrated significant potential bias of operators in both field and laboratory. This is the first documented case demonstrating the significant influence of observer bias on results from invertebrate field-based studies. Examples of two long-term trials are also given that illustrate further operator bias. Our results suggest that long-term ecological studies using invertebrates need to be rigorously audited to ensure that operator bias is accounted for during analysis and interpretation. Further, taxonomic harmonisation remains an important step in merging field and laboratory data collected by different operators.

3-D video techniques in endoscopic surgery.

PubMed

Becker, H; Melzer, A; Schurr, M O; Buess, G

1993-02-01

Three-dimensional visualisation of the operative field is an important requisite for precise and fast handling of open surgical operations. Up to now it has only been possible to display a two-dimensional image on the monitor during endoscopic procedures. The increasing complexity of minimal invasive interventions requires endoscopic suturing and ligatures of larger vessels which are difficult to perform without the impression of space. Three-dimensional vision therefore may decrease the operative risk, accelerate interventions and widen the operative spectrum. In April 1992 a 3-D video system developed at the Nuclear Research Center Karlsruhe, Germany (IAI Institute) was applied in various animal experimental procedures and clinically in laparoscopic cholecystectomy. The system works with a single monitor and active high-speed shutter glasses. Our first trials with this new 3-D imaging system clearly showed a facilitation of complex surgical manoeuvres like mobilisation of organs, preparation in the deep space and suture techniques. The 3-D-system introduced in this article will enter the market in 1993 (Opticon Co., Karlsruhe, Germany.

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

Melody, M.

Waste Technologies Industries (WTI; East Liverpool, Ohio) is trying to wing what it hopes will be its final battle in a 13-year, $160 million war with the government, and community and environmental groups. The company since 1980 has sought EPA approval to operate a hazardous waste incinerator in East Liverpool, Ohio. WTI late last year conducted a pre-test burn, or shakedown, during which the incinerator burned certain types of hazardous waste. The test demonstrates the incinerator's performance under normal operating conditions, Regulatory authorities, including EPA and the Ohio Environmental Protection Agency (OEPA), monitored activity during the shakedown, which was limitedmore » to 720 hours of operation. In accordance with RCRA requirements, the company in March conducted a trial burn to demonstrate that the incinerator meets permit standards. WTI's permit specifies three performance parameters the incinerator must meet -- particulate and hydrogen chloride emissions limits, and destruction removal efficiencies (DREs).« less

Risk factors for urinary tract infection following incontinence surgery.

PubMed

Nygaard, Ingrid; Brubaker, Linda; Chai, Toby C; Markland, Alayne D; Menefee, Shawn A; Sirls, Larry; Sutkin, Gary; Zimmern, Phillipe; Arisco, Amy; Huang, Liyuan; Tennstedt, Sharon; Stoddard, Anne

2011-10-01

The purpose of this study is to describe risk factors for post-operative urinary tract infection (UTI) the first year after stress urinary incontinence surgery. Multivariable logistic regression analyses were performed on data from 1,252 women randomized in two surgical trials, Stress Incontinence Surgical Treatment Efficacy trial (SISTEr) and Trial Of Mid-Urethral Slings (TOMUS). Baseline recurrent UTI (rUTI; ≥3 in 12 months) increased the risk of UTI in the first 6 weeks in both study populations, as did sling procedure and self-catheterization in SISTEr, and bladder perforation in TOMUS. Baseline rUTI, UTI in the first 6 weeks, and PVR > 100 cc at 12 months were independent risk factors for UTI between 6 weeks and 12 months in the SISTEr population. Few (2.3-2.4%) had post-operative rUTI, precluding multivariable analysis. In women with pre-operative rUTI, successful surgery (negative cough stress test) at 1 year did not appear to decrease the risk of persistent rUTI. Pre-operative rUTI is the strongest risk factor for post-operative UTI.

The effectiveness of dry-cupping in preventing post-operative nausea and vomiting by P6 acupoint stimulation: A randomized controlled trial.

PubMed

Farhadi, Khosro; Choubsaz, Mansour; Setayeshi, Khosro; Kameli, Mohammad; Bazargan-Hejazi, Shahrzad; Heidari Zadie, Zahra; Ahmadi, Alireza

2016-09-01

Postoperative nausea and vomiting (PONV) is a common complication after general anesthesia, and the prevalence ranges between 25% and 30%. The aim of this study was to determine the preventive effects of dry cupping on PONV by stimulating point P6 in the wrist. This was a randomized controlled trial conducted at the Imam Reza Hospital in Kermanshah, Iran. The final study sample included 206 patients (107 experimental and 99 controls). Inclusion criteria included the following: female sex; age>18 years; ASA Class I-II; type of surgery: laparoscopic cholecystectomy; type of anesthesia: general anesthesia. Exclusion criteria included: change in the type of surgery, that is, from laparoscopic cholecystectomy to laparotomy, and ASA-classification III or more. Interventions are as follows: pre surgery, before the induction of anesthesia, the experimental group received dry cupping on point P6 of the dominant hand's wrist with activation of intermittent negative pressure. The sham group received cupping without activation of negative pressure at the same point. Main outcome was that the visual analogue scale was used to measure the severity of PONV. The experimental group who received dry cupping had significantly lower levels of PONV severity after surgery (P < 0.001) than the control group. The differences in measure were maintained after controlling for age and ASA in regression models (P < 0.01). Traditional dry cupping delivered in an operation room setting prevented PONV in laparoscopic cholecystectomy patients.

Distinct brain networks for adaptive and stable task control in humans

PubMed Central

Dosenbach, Nico U. F.; Fair, Damien A.; Miezin, Francis M.; Cohen, Alexander L.; Wenger, Kristin K.; Dosenbach, Ronny A. T.; Fox, Michael D.; Snyder, Abraham Z.; Vincent, Justin L.; Raichle, Marcus E.; Schlaggar, Bradley L.; Petersen, Steven E.

2007-01-01

Control regions in the brain are thought to provide signals that configure the brain's moment-to-moment information processing. Previously, we identified regions that carried signals related to task-control initiation, maintenance, and adjustment. Here we characterize the interactions of these regions by applying graph theory to resting state functional connectivity MRI data. In contrast to previous, more unitary models of control, this approach suggests the presence of two distinct task-control networks. A frontoparietal network included the dorsolateral prefrontal cortex and intraparietal sulcus. This network emphasized start-cue and error-related activity and may initiate and adapt control on a trial-by-trial basis. The second network included dorsal anterior cingulate/medial superior frontal cortex, anterior insula/frontal operculum, and anterior prefrontal cortex. Among other signals, these regions showed activity sustained across the entire task epoch, suggesting that this network may control goal-directed behavior through the stable maintenance of task sets. These two independent networks appear to operate on different time scales and affect downstream processing via dissociable mechanisms. PMID:17576922

Intervention-related increases in preoperative physical activity are maintained 6-months after Bariatric surgery: results from the bari-active trial.

PubMed

Bond, D S; Thomas, J G; Vithiananthan, S; Unick, J; Webster, J; Roye, G D; Ryder, B A; Sax, H C

2017-03-01

Higher preoperative physical activity (PA) strongly predicts higher post-operative PA in bariatric surgery (BS) patients, providing rationale for preoperative PA interventions (PAIs). However, whether PAI-related increases can be maintained post-operatively has not been examined. This study compared PA changes across pre- (baseline, post-intervention) and post-operative (6-month follow up) periods in participants randomized to 6 weeks of preoperative PAI or standard care control (SC). Of 75 participants initially randomized, 36 (PAI n=22; SC n=14) underwent BS. Changes in daily bout-related (⩾10-min bouts) moderate-to-vigorous PA (MVPA) and steps were assessed via the SenseWear Armband monitor. PAI received weekly counseling to increase walking exercise. Retention (86%) at post-operative follow up was similar between groups. Intent-to-treat analyses showed that PAI vs SC had greater increases across time (baseline, post-intervention, follow up) in bout-related MVPA minutes/day (4.3±5.1, 26.3±21.3, 28.7±26.3 vs 10.4±22.9, 11.4±16.0, 18.5±28.2; P=0.013) and steps/day (5163±2901, 7950±3286, 7870±3936 vs 5163±2901, 5601±3368, 5087±2603; P<0.001). PAI differed from SC on bout-related MVPA at post-intervention (P=0.016; d=0.91), but not follow up (P=0.15; d=0.41), and steps at post-intervention (P=0.031; d=0.78) and follow up (P=0.024; d=0.84). PAI participants maintained preoperative PA increases post-operatively. Findings support preoperative PAIs and research to test whether PA changes can be sustained and influence surgical outcomes beyond the initial post-operative period.

Cost-evaluation model for clinical trials in a hospital pharmacy service.

PubMed

Idoate, A; Ortega, A; Carrera, F J; Aldaz, A; Giráldez, J

1995-09-22

A cost-evaluation model was applied to clinical trial protocols to estimate their cost for the hospital pharmacy service. The steps taken in the drug management of clinical research were identified. Fixed costs (common to all clinical trials) and variable costs (peculiar to each clinical trial) were determined for each step. The number of patients, the number of operations, the planned services (receptions, storage, drug dispensing), the timing and difficulty of the study (randomization) were included in the variable costs. The economic assessment of these items was based on the costs of the materials and means used, the cost of staff time and finally the cost of drug storage during the clinical trial. This model was applied to 24 clinical trials carried out in the University Clinic of Navarra. 83% of all pharmacy costs of a clinical trial were variable. Drug dispensing, stock management and return drugs account for 94% of the time expended. The approximate cost of the pharmacy providing investigational services was $1,766 per trial or $174 per patient. Drug storage costs were not an important source of expenditure among the variable costs (7.4%). The best way to determine the cost of a trial is to calculate the number of operations.

Does caffeine reduce postoperative bowel paralysis after elective laparoscopic colectomy? (CaCo trial): study protocol for a randomized controlled trial.

PubMed

Kruse, Christina; Müller, Sascha A; Warschkow, René; Lüthi, Cornelia; Brunner, Walter; Marti, Lukas; Sulz, Michael Christian; Schmied, Bruno M; Tarantino, Ignazio; Beutner, Ulrich

2016-04-04

Postoperative bowel paralysis is common after abdominal operations, including colectomy. As a result, hospitalization may be prolonged, thereby leading to increased cost. A recent randomized controlled trial showed that the consumption of regular black coffee after colectomy is associated with a significantly faster resumption of intestinal motility. The mechanism by which coffee stimulates intestinal motility is unknown, but caffeine seems to be the most likely stimulating agent. Thus, the effect of caffeine on postoperative bowel activity after colon surgery will be analyzed in this trial, herein referred to as CaCo. Patients scheduled for elective laparoscopic colectomy or upper rectum resection are eligible to participate in this double-blinded, placebo-controlled, randomized trial. Patients fulfilling all inclusion criteria will be allocated after the surgical procedure to one of three treatment arms: 100 mg caffeine, 200 mg caffeine, or placebo (corn starch). Patients will take the capsules containing the study medication three times daily with a meal. The primary endpoint of the study is the time to a solid bowel movement. The study treatment will be stopped after the patient produces a solid bowel movement or has taken ten capsules, whichever occurs first. To determine the colonic passage time, patients will take a capsule with radiopaque markers at breakfast for the first 3 days after surgery. On the fourth day, the location of the markers will be determined with an abdominal X-ray scan. Further secondary objectives are the postoperative morbidity and mortality, well-being, sleeping behavior, and length of hospital stay. The study size was calculated to be 180 patients with an interim analysis occurring after 60 patients. From a previous study investigating coffee, evidence exists that caffeine might have a positive influence on the postoperative bowel activity. This double-blinded, placebo-controlled, randomized trial tries to show that caffeine will shorten the postoperative bowel paralysis and, thus, will improve recovery and shorten the hospital stay after colon surgery. Clinicaltrials.gov NCT02510911 Swiss National Clinical Trials Portal SNCTP000001131.

Early assessment of bilateral inguinal hernia repair: A comparison between the laparoscopic total extraperitoneal and Stoppa approaches.

PubMed

Utiyama, Edivaldo Massazo; Damous, S Rgio Henrique Bastos; Tanaka, Eduardo Yassushi; Yoo, Jin Hwan; de Miranda, Jocielle Santos; Ushinohama, Adriano Zuardi; Faro, Mario Paulo; Birolini, Claudio Augusto Vianna

2016-01-01

The present clinical trial was designed to compare the results of bilateral inguinal hernia repair between patients who underwent the conventional Stoppa technique and laparoscopic total extraperitoneal repair (LTE) with a single mesh and without staple fixation. This controlled, randomised clinical trial was conducted at General Surgery and Trauma of the Clinics Hospital, Medical School, the University of São Paulo between September 2010 and February 2011. Totally, 50 male patients, with a bilateral inguinal hernia, older than 25 years were considered eligible for the study. The following parameters were analysed during the early post-operative period: (1) The intensity of surgical trauma, operation time, C-reactive protein (CRP) levels, white blood cell count, bleeding and pain intensity; (2) quality of life assessment; and (3) post-operative complications. LTE procedure was longer than the Stoppa procedure (134.6 min ± 38.3 vs. 90.6 min ± 41.3; P < 0.05). The levels of CRP were higher in the Stoppa group (P < 0.05) but the number of leucocytes, haematocrit, and haemoglobin were similar between the groups (P > 0.05). There was no difference in pain during the 1st and 7th post-operative, physical functioning, physical limitation, the impact of pain on daily activities, and the Carolinas Comfort Scale during the 7th and 15th post-operative (P > 0.05). Complications occurred in 88% of Stoppa group (22 patients) and 64% in LTE group (16 patients) (P < 0.05). The comparative study between the Stoppa and LTE approaches for the bilateral inguinal hernia repair demonstrated that: (1) The LTE approach showed less surgical trauma despite the longer operation time; (2) Quality of life during the early post-operative period were similar; and (3) Complication rates were higher in the Stoppa group.

Early assessment of bilateral inguinal hernia repair: A comparison between the laparoscopic total extraperitoneal and Stoppa approaches

PubMed Central

Utiyama, Edivaldo Massazo; Damous, Sérgio Henrique Bastos; Tanaka, Eduardo Yassushi; Yoo, Jin Hwan; de Miranda, Jocielle Santos; Ushinohama, Adriano Zuardi; Faro, Mario Paulo; Birolini, Claudio Augusto Vianna

2016-01-01

BACKGROUND: The present clinical trial was designed to compare the results of bilateral inguinal hernia repair between patients who underwent the conventional Stoppa technique and laparoscopic total extraperitoneal repair (LTE) with a single mesh and without staple fixation. PATIENTS AND METHODS: This controlled, randomised clinical trial was conducted at General Surgery and Trauma of the Clinics Hospital, Medical School, the University of São Paulo between September 2010 and February 2011. Totally, 50 male patients, with a bilateral inguinal hernia, older than 25 years were considered eligible for the study. The following parameters were analysed during the early post-operative period: (1) The intensity of surgical trauma, operation time, C-reactive protein (CRP) levels, white blood cell count, bleeding and pain intensity; (2) quality of life assessment; and (3) post-operative complications. RESULTS: LTE procedure was longer than the Stoppa procedure (134.6 min ± 38.3 vs. 90.6 min ± 41.3; P < 0.05). The levels of CRP were higher in the Stoppa group (P < 0.05) but the number of leucocytes, haematocrit, and haemoglobin were similar between the groups (P > 0.05). There was no difference in pain during the 1st and 7th post-operative, physical functioning, physical limitation, the impact of pain on daily activities, and the Carolinas Comfort Scale during the 7th and 15th post-operative (P > 0.05). Complications occurred in 88% of Stoppa group (22 patients) and 64% in LTE group (16 patients) (P < 0.05). CONCLUSION: The comparative study between the Stoppa and LTE approaches for the bilateral inguinal hernia repair demonstrated that: (1) The LTE approach showed less surgical trauma despite the longer operation time; (2) Quality of life during the early post-operative period were similar; and (3) Complication rates were higher in the Stoppa group. PMID:27279401

Pre-operative nutrition support in patients undergoing gastrointestinal surgery.

PubMed

Burden, Sorrel; Todd, Chris; Hill, James; Lal, Simon

2012-11-14

Post-operative management in gastrointestinal (GI) surgery is becoming well established with 'Enhanced Recovery After Surgery' protocols starting 24 hours prior to surgery with carbohydrate loading and early oral or enteral feeding given to patients the first day following surgery. However, whether or not nutritional intervention should be initiated earlier in the preoperative period remains unclear. Poor pre-operative nutritional status has been linked consistently to an increase in post-operative complications and poorer surgical outcome. To review the literature on preoperative nutritional support in patients undergoing gastrointestinal surgery (GI). The searches were initially run in March 2011 and subsequently updated in February 2012. Databases including all EBM Reviews (Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA and NHSEED) MEDLINE, EMBASE, AMED, British Nursing Index Archive using OvidSP were included and a search was run on each database separately after which duplicates were excluded. The inclusion criteria were randomised controlled trials that evaluated pre-operative nutritional support in GI surgical participants using a nutritional formula delivered by a parenteral, enteral or oral route. The primary outcomes included post-operative complications and length of hospital stay. Two observers screened the abstracts for inclusion in the review and performed data extraction. Bias was assessed for each of the included studies using the bias assessment tables in the Cochrane Software Review Manager (version 5.1, Cochrane Collaboration). The trials were analysed using risk ratios with Mantel-Haenszel in fixed effects methods displayed with heterogeneity. Meta-analyses were undertaken on trials evaluating immune enhancing (IE) nutrition, standard oral supplements, enteral and parenteral nutrition (PN) which were administered pre-operatively.Study characteristics were summarised in tables. Dichotomous and ratio data were entered into meta-analyses for the primary outcomes. These were then summarised in tables with assumed and corresponding risk with relative effect giving 95% confidence intervals. The searches identified 9900 titles and, after excluding duplicates, 6433 titles were initially screened. After the initial title screen, 6266 were excluded. Abstracts were screened for 167 studies and 33 articles were identified as meeting the inclusion criteria, of which 13 were included in the review after an assessment of the complete manuscripts.Seven trials evaluating IE nutrition were included in the review, of which 6 were combined in a meta-analysis. These studies showed a low to moderate level of heterogeneity and significantly reduced total post-operative complications (risk ratio (RR) 0.67 CI 0.53 to 0.84). Three trials evaluating PN were included in a meta-analysis and a significant reduction in post-operative complications was demonstrated (RR 0.64 95% CI 0.46 to 0.87) with low heterogeneity, in predominantly malnourished participants. Two trials evaluating enteral nutrition (RR 0.79, 95% CI 0.56 to 1.10) and 3 trials evaluating standard oral supplements (RR 1.01 95% CI 0.56 to 1.10) were included, neither of which showed any difference in the primary outcomes. There have been significant benefits demonstrated with pre-operative administration of IE nutrition in some high quality trials. However, bias was identified which may limit the generalizability of these results to all GI surgical candidates and the data needs to be placed in context with other recent innovations in surgical management (eg-ERAS). Some unwanted effects have also been reported with components of IE nutrition in critical care patients and it is unknown whether there would be detrimental effects by administering IE nutrition to patients who could require critical care support after their surgery. The studies evaluating PN demonstrated that the provision of PN to predominantly malnourished surgical candidates reduced post-operative complications; however, these data may not be applicable to current clinical practice, not least because they have involved a high degree of 'hyperalimentation'. Trials evaluating enteral or oral nutrition were inconclusive and further studies are required to select GI surgical patients for these nutritional interventions.

A randomized controlled trial of nonoperative treatment versus open reduction and internal fixation for stable, displaced, partial articular fractures of the radial head: the RAMBO trial

PubMed Central

2014-01-01

Background The choice between operative or nonoperative treatment is questioned for partial articular fractures of the radial head that have at least 2 millimeters of articular step-off on at least one radiograph (defined as displaced), but less than 2 millimeter of gap between the fragments (defined as stable) and that are not associated with an elbow dislocation, interosseous ligament injury, or other fractures. These kinds of fractures are often classified as Mason type-2 fractures. Retrospective comparative studies suggest that operative treatment might be better than nonoperative treatment, but the long-term results of nonoperative treatment are very good. Most experts agree that problems like reduced range of motion, painful crepitation, nonunion or bony ankylosis are infrequent with both nonoperative and operative treatment of an isolated displaced partial articular fracture of the radial head, but determining which patients will have problems is difficult. A prospective, randomized comparison would help minimize bias and determine the balance between operative and nonoperative risks and benefits. Methods/Design The RAMBO trial (Radial Head – Amsterdam – Amphia – Boston - Others) is an international prospective, randomized, multicenter trial. The primary objective of this study is to compare patient related outcome defined by the ‘Disabilities of Arm, Shoulder and Hand (DASH) score’ twelve months after injury between operative and nonoperative treated patients. Adult patients with partial articular fractures of the radial head that comprise at least 1/3rd of the articular surface, have ≥ 2 millimeters of articular step-off but less than 2 millimeter of gap between the fragments will be enrolled. Secondary outcome measures will be the Mayo Elbow Performance Index (MEPI), the Oxford Elbow Score (OES), pain intensity through the ‘Numeric Rating Scale’, range of motion (flexion arc and rotational arc), radiographic appearance of the fracture (heterotopic ossification, radiocapitellar and ulnohumeral arthrosis, fracture healing, and signs of implant loosening or breakage) and adverse events (infection, nerve injury, secondary interventions) after one year. Discussion The successful completion of this trial will provide evidence on the best treatment for stable, displaced, partial articular fractures of the radial head. Trial registration The trial is registered at the Dutch Trial Register: NTR3413. PMID:24885637

The effect of an antibacterial washing-up liquid in reducing dishwater aerobic plate counts.

PubMed

Holah, J T; Hall, K E

2006-05-01

To assess any significant differences in the aerobic plate count (APC) of catering dishwaters following the use of a traditional, nonantibacterial or an antibacterial washing-up liquid. A dishwashing trial was undertaken within a commercial restaurant of 6 weeks duration (3 weeks with each washing-up liquid in a randomized, weekly pattern). Five replicate samples were taken from the dishwater at the end of the washing-up operation, on three separate occasions each day corresponding to mid-morning, lunchtime and mid-afternoon meal preparations. The antibacterial product was shown to significantly reduce the APC by an average log10 reduction of 1.81 CFU ml(-1) (98.5%) as compared with the traditional product. APC were lower for each of the three weekly time periods for the antibacterial product. Continued use of the antibacterial product did not decrease the APC of the dishwater, though with the traditional product, dishwater counts increased throughout the trial week. Antibacterial washing-up liquids, with proven activity in controlling levels of microorganisms in dishwaters, could play a significant role in reducing the risk of cross-contamination between washed articles during washing-up operations.

Wide excision of soft tissues adjacent to the ovary and fallopian tube does not impair the ovarian reserve in women undergoing prophylactic bilateral salpingectomy: results from a randomized, controlled trial.

PubMed

Venturella, Roberta; Morelli, Michele; Lico, Daniela; Di Cello, Annalisa; Rocca, Morena; Sacchinelli, Angela; Mocciaro, Rita; D'Alessandro, Pietro; Maiorana, Antonio; Gizzo, Salvatore; Zullo, Fulvio

2015-11-01

To study the effects of the wide excision of soft tissues adjacent to the ovary and fallopian tube on ovarian function and surgical outcomes in women undergoing laparoscopic bilateral prophylactic salpingectomy. Randomized, controlled trial. Teaching hospital. One hundred eighty-six women undergoing laparoscopic surgery for uterine myoma (n = 143) or tubal surgical sterilization (n = 43). Patients were randomly divided into two groups. In group A (n = 91), standard salpingectomy was performed. In group B (n = 95), the mesosalpinx was removed within the tubes. Prior to and 3 months after surgery, antimüllerian hormone (AMH), FSH, three-dimensional antral follicle count (AFC), vascular index (VI), flow index (FI), vascular-flow index (VFI), and OvAge were recorded for each patient. Ovarian reserve modification (Δ) before and after surgery was assessed as the primary outcome. Operative time, variation of the hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were assessed as secondary outcomes. No significant difference was observed between groups for ΔAMH, ΔFSH, ΔAFC, ΔVI, ΔFI, ΔVFI, and ΔOvAge. Moreover, the groups were similar for operative time, ΔHb, postoperative hospital stay, postoperative return to normal activity, and complication rate. Even when the surgical excision includes the removal of the mesosalpinx, salpingectomy does not damage the ovarian reserve. Moreover, wide salpingectomy with excision of the mesosalpinx did not alter blood loss, hospitalization stay, or return to normal activities. NCT02086370. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Improvement of Pediatric Drug Development: Regulatory and Practical Frameworks.

PubMed

Tsukamoto, Katusra; Carroll, Kelly A; Onishi, Taku; Matsumaru, Naoki; Brasseur, Daniel; Nakamura, Hidefumi

2016-03-01

A dearth in pediatric drug development often leaves pediatricians with no alternative but to prescribe unlicensed or off-label drugs with a resultant increased risk of adverse events. We present the current status of pediatric drug development and, based on our data analysis, clarify the problems in this area. Further action is proposed to improve the drug development that has pediatric therapeutic orphan status. We analyzed all Phase II/III and Phase III trials in ClinicalTrials.gov that only included pediatric participants (<18 years old) between 2006 and 2014. Performance index, an indicator of pediatric drug development, was calculated by dividing the annual number of pediatric clinical trials by million pediatric populations acquired from Census.gov. Effects of the 2 Japanese premiums introduced in 2010, for the enhancement of pediatric drug development, were analyzed by comparing mean performance index prepremiums (2006-2009) and postpremiums (2010-2014) among Japan, the European Union, and the United States. The European Union Clinical Trials Register and published reports from the European Medicines Agency were also surveyed to investigate the Paediatric Committee effect on pediatric clinical trials in the European Union. Mean difference of the performance index in prepremiums and postpremiums between Japan and the European Union were 0.296 (P < 0.001) and 0.066 (P = 0.498), respectively. Those between Japan and the United States were 0.560 (P < 0.001) and 0.281 (P = 0.002), indicating that pediatric drug development in Japan was more active after the introduction of these premiums, even reaching the level of the European Union. The Pediatric Regulation and the Paediatric Committee promoted pediatric drug development in the European Union. The registered number of clinical trials that includes at least 1 participants <18 years old in the European Union Clinical Trials Register increased by 247 trials (from 672) in the 1000 days after regulation. The ratio of pediatric clinical trials with an approved Paediatric Investigation Plan increased to >15% after 2008. Recruitment and ethical obstacles make conducting pediatric clinical trials challenging. An improved operational framework for conducting clinical trials should mirror the ever-improving regulatory framework that incentivizes investment in pediatric clinical trials. Technological approaches, enhancements in electronic medical record systems, and community approaches that actively incorporate input from physicians, researchers, and patients could offer a sustainable solution to recruitment of pediatric study participants. The key therefore is to improve pediatric pharmacotherapy collaboration among industry, government, academia, and community. Expanding the regulatory steps taken in the European Union, United States, and Japan and using innovative clinical trial tools can move pediatric pharmacotherapy out of its current therapeutic orphan state. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Robotic assistants in personal care: A scoping review.

PubMed

Bilyea, A; Seth, N; Nesathurai, S; Abdullah, H A

2017-11-01

The aim of this study is to present an overview of the technological advances in the field of robotics developed for assistance with activities of daily living (ADL), and to present areas where further research is required. Four databases were searched for articles presenting either a novel design of one of these personal care robotic system or trial results relating to these systems. Articles presenting nine different robotic personal care systems were examined, six of which had been developed after 2005. These six also all have publications relating to their trials. In the majority of trials, patient independence was improved with operation of the robotic device for a specific subset of ADL. A map of the current state of the field of personal care robotics is presented in this study. Areas requiring further research include improving feedback and awareness, as well as refining control methods and pre-programmed behaviors. Developing an affordable, easy to use system would help fill the current gap in the commercial market. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Antibiotic prophylaxis in permanent pacemaker implantation: a prospective randomised trial.

PubMed Central

Mounsey, J P; Griffith, M J; Tynan, M; Gould, F K; MacDermott, A F; Gold, R G; Bexton, R S

1994-01-01

BACKGROUND--Pacemaker pocket infection is a potentially serious problem after permanent pacemaker implantation. Antibiotic prophylaxis is commonly prescribed to reduce the incidence of this complication, but current trial evidence of its efficacy is conflicting. A large prospective randomised trial was therefore performed of antibiotic prophylaxis in permanent pacemaker implantation. The intention was firstly to determine whether antibiotic prophylaxis is efficacious in these patients and secondly to identify which patients are at the highest risk of infection. METHODS--A prospective randomised open trial of flucloxacillin (clindamycin if the patient was allergic to penicillin) v no antibiotic was performed in a cohort of patients undergoing first implantation of a permanent pacing system over a 17 month period. Intravenous antibiotics were started at the time of implantation and continued for 48 hours. The trial endpoint was a repeat operation for an infective complication. RESULTS--473 patients were entered into a randomised trial. 224 received antibiotic prophylaxis and 249 received no antibiotics. A further 183 patients were not randomised but were treated according to the operator's preference (64 antibiotics, 119 no antibiotics); these patients are included only in the analysis of predictors of infection. Patients were followed up for a mean (SD) of 19(5) months. Among the patients in the randomised group there were nine infections requiring a repeat operation, all in the group not receiving antibiotic (P = 0.003). In the total patient cohort there were 13 infections, all but one in the non-antibiotic group (P = 0.006). Nine of the infections presented as erosion of the pulse generator or electrode, three as septicaemia secondary to Staphylococcus aureus, and one as a pocket abscess secondary to Staphylococcus epidermidis. Infections were significantly more common when the operator was inexperienced (< or = 100 previous patients), the operation was prolonged, or after a repeat operation for non-infective complications (principally lead displacement). Infection was not significantly more common in patients identified preoperatively as being at high risk (for example patients with diabetes mellitus, patients receiving long term steroid treatment), although there was a trend in this direction. CONCLUSIONS--Antibiotic prophylaxis significantly reduced the incidence of infective complications requiring a repeat operation after permanent pacemaker implantation. It is suggested that antibiotics should be used routinely. PMID:7833191

A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change?

PubMed

Dean, B J F; Jones, L D; Palmer, A J R; Macnair, R D; Brewer, P E; Jayadev, C; Wheelton, A N; Ball, D E J; Nandra, R S; Aujla, R S; Sykes, A E; Carr, A J

2016-05-01

The PROximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial has recently demonstrated that surgery is non-superior to non-operative treatment in the management of displaced proximal humeral fractures. The objective of this study was to assess current surgical practice in the context of the PROFHER trial in terms of patient demographics, injury characteristics and the nature of the surgical treatment. A total of ten consecutive patients undergoing surgery for the treatment of a proximal humeral fracture from each of 11 United Kingdom hospitals were retrospectively identified over a 15 month period between January 2014 and March 2015. Data gathered for the 110 patients included patient demographics, injury characteristics, mode of surgical fixation, the grade of operating surgeon and the cost of the surgical implants. A majority of the patients were female (66%, 73 of 110). The mean patient age was 62 years (range 18 to 89). A majority of patients met the inclusion criteria for the PROFHER trial (75%, 83 of 110). Plate fixation was the most common mode of surgery (68%, 75 patients), followed by intramedullary fixation (12%, 13 patients), reverse shoulder arthroplasty (10%, 11 patients) and hemiarthroplasty (7%, eight patients). The consultant was either the primary operating surgeon or supervising the operating surgeon in a large majority of cases (91%, 100 patients). Implant costs for plate fixation were significantly less than both hemiarthroplasty (p < 0.05) and reverse shoulder arthroplasty (p < 0.0001). Implant costs for intramedullary fixation were significantly less than plate fixation (p < 0.01), hemiarthroplasty (p < 0.0001) and reverse shoulder arthroplasty (p < 0.0001). Our study has shown that the majority of a representative sample of patients currently undergoing surgical treatment for a proximal humeral fracture in these United Kingdom centres met the inclusion criteria for the PROFHER trial and that a proportion of these patients may, therefore, have been effectively managed non-operatively.Cite this article: Mr B. J. F. Dean. A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change? Bone Joint Res 2016;5:178-184. DOI: 10.1302/2046-3758.55.2000596. © 2016 Dean et al.

Transforming the Activation of Clinical Trials.

PubMed

Watters, Julie T; Pitzen, Jason H; Sanders, Linda J; Bruce, Virginia Nickie M; Cornell, Alissa R; Cseko, Gary C; Grace, Janice S; Kwon, Pamela S; Kukla, Andrea K; Lee, Michael S; Monosmith, Michelle D; Myren, John D; Kottschade, Rebecca S; Shaft, Marc N; Weis, Jennifer Jenny A; Welter, Jane C; Bharucha, Adil E

2018-01-01

The Institute of Medicine and US Food and Drug Administration (FDA) recognize that activating clinical trials in the United States is lengthy and inefficient. Downstream consequences include increased expense, suboptimal accrual, move of clinical trials overseas, and delayed availability of treatments for patients. An in-tandem processing initiative is here highlighted that transformed the activation of clinical trials (TACT), reduced the activation time by 70%, and offers a paradigm for enhanced translational readiness. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Human striatal activation during adjustment of the response criterion in visual word recognition.

PubMed

Kuchinke, Lars; Hofmann, Markus J; Jacobs, Arthur M; Frühholz, Sascha; Tamm, Sascha; Herrmann, Manfred

2011-02-01

Results of recent computational modelling studies suggest that a general function of the striatum in human cognition is related to shifting decision criteria in selection processes. We used functional magnetic resonance imaging (fMRI) in 21 healthy subjects to examine the hemodynamic responses when subjects shift their response criterion on a trial-by-trial basis in the lexical decision paradigm. Trial-by-trial criterion setting is obtained when subjects respond faster in trials following a word trial than in trials following nonword trials - irrespective of the lexicality of the current trial. Since selection demands are equally high in the current trials, we expected to observe neural activations that are related to response criterion shifting. The behavioural data show sequential effects with faster responses in trials following word trials compared to trials following nonword trials, suggesting that subjects shifted their response criterion on a trial-by-trial basis. The neural responses revealed a signal increase in the striatum only in trials following word trials. This striatal activation is therefore likely to be related to response criterion setting. It demonstrates a role of the striatum in shifting decision criteria in visual word recognition, which cannot be attributed to pure error-related processing or the selection of a preferred response. Copyright © 2010 Elsevier Inc. All rights reserved.

Stakeholder involvement in the design of a patient-centered comparative effectiveness trial of the "On the Move" group exercise program in community-dwelling older adults.

PubMed

Brach, Jennifer S; Perera, Subashan; Gilmore, Sandra; VanSwearingen, Jessie M; Brodine, Deborah; Wert, David; Nadkarni, Neelesh K; Ricci, Edmund

2016-09-01

Group exercise programs for older adults often exclude the timing and coordination of movement. Stakeholder involvement in the research process is strongly encouraged and improves the relevance and adoption of findings. We describe stakeholder involvement in the design of a clinical trial of a group-based exercise program that incorporates timing and coordination of movement into the exercises. The study was a cluster randomized, single-blind intervention trial to compare the effects on function, disability and mobility of a standard group exercise program and the "On the Move" group exercise program in older adults residing in independent living facilities and senior apartment buildings, and attending community centers. Exercise classes were twice weekly for 12weeks delivered by study exercise leaders and facility activity staff personnel. The primary outcomes function, disability and mobility were assessed at baseline and post-intervention. Function and disability were assessed using the Late Life Function and Disability Instrument, and mobility using the Six-Minute Walk Test and gait speed. Patient and provider stakeholders had significant input into the study aims, design, sample, intervention, outcomes and operational considerations. A community-based exercise program to improve walking can be developed to address both investigator identified missing components in current exercise to improve walking and stakeholder defined needs and interest for the activity program. Involvement of stakeholders substantially improves the relevance of research questions, increases the transparency of research activities and may accelerate the adoption of research into practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Stakeholder involvement in the design of a patient-centered comparative effectiveness trial of the “On the Move” group exercise program in community-dwelling older adults

PubMed Central

Brach, Jennifer S.; Perera, Subashan; Gilmore, Sandra; VanSwearingen, Jessie M.; Brodine, Deborah; Wert, David; Nadkarni, Neelesh K.; Ricci, Edmund

2016-01-01

Background Group exercise programs for older adults often exclude the timing and coordination of movement. Stakeholder involvement in the research process is strongly encouraged and improves the relevance and adoption of findings. We describe stakeholder involvement in the design of a clinical trial of a group-based exercise program that incorporates timing and coordination of movement into the exercises. Methods The study was a cluster randomized, single-blind intervention trial to compare the effects on function, disability and mobility of a standard group exercise program and the “On the Move” group exercise program in older adults residing in independent living facilities and senior apartment buildings, and attending community centers. Exercise classes were twice weekly for 12 weeks delivered by study exercise leaders and facility activity staff personnel. Outcomes The primary outcomes function, disability and mobility were assessed at baseline and post-intervention. Function and disability were assessed using the Late Life Function and Disability Instrument, and mobility using the Six-Minute Walk Test and gait speed. Stakeholders Patient and provider stakeholders had significant input into the study aims, design, sample, intervention, outcomes and operational considerations. Summary A community-based exercise program to improve walking can be developed to address both investigator identified missing components in current exercise to improve walking and stakeholder defined needs and interest for the activity program. Involvement of stakeholders substantially improves the relevance of research questions, increases the transparency of research activities and may accelerate the adoption of research into practice. PMID:27521806

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial.

PubMed

Hackshaw-McGeagh, Lucy; Lane, J Athene; Persad, Raj; Gillatt, David; Holly, Jeff M P; Koupparis, Anthony; Rowe, Edward; Johnston, Lyndsey; Cloete, Jenny; Shiridzinomwa, Constance; Abrams, Paul; Penfold, Chris M; Bahl, Amit; Oxley, Jon; Perks, Claire M; Martin, Richard

2016-03-07

A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

PubMed Central

Eaton, Simon; Abbo, Olivier; Arnaud, Alexis P; Beaudin, Marianne; Brindle, Mary; Bütter, Andreana; Davies, Dafydd; Jancelewicz, Tim; Johnson, Kathy; Keijzer, Richard; Lapidus-Krol, Eveline; Offringa, Martin; Piché, Nelson; Rintala, Risto; Skarsgard, Erik; Svensson, Jan F; Ungar, Wendy J; Wester, Tomas; Willan, Andrew R; Zani, Augusto; St Peter, Shawn D; Pierro, Agostino

2017-01-01

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016. PMID:29637088

The Effects of Industry Sponsorship on Comparator Selection in Trial Registrations for Neuropsychiatric Conditions in Children

PubMed Central

Dunn, Adam G.; Mandl, Kenneth D.; Coiera, Enrico; Bourgeois, Florence T.

2013-01-01

Pediatric populations continue to be understudied in clinical drug trials despite the increasing use of pharmacotherapy in children, particularly with psychotropic drugs. Most pertinent to the clinical selection of drug interventions are trials directly comparing drugs against other drugs. The aim was to measure the prevalence of active drug comparators in neuropsychiatric drug trials in children and identify the effects of funding source on comparator selection. We analyzed the selection of drugs and drug comparisons in clinical trials registered between January 2006 and May 2012. Completed and ongoing interventional trials examining treatments for six neuropsychiatric conditions in children were included. Networks of drug comparisons for each condition were constructed using information about the trial study arms. Of 421 eligible trial registrations, 228 (63,699 participants) were drug trials addressing ADHD (106 trials), autism spectrum disorders (47), unipolar depression (16), seizure disorders (38), migraines and other headaches (15), or schizophrenia (11). Active drug comparators were used in only 11.0% of drug trials while 44.7% used a placebo control and 44.3% no drug or placebo comparator. Even among conditions with well-established pharmacotherapeutic options, almost all drug interventions were compared to a placebo. Active comparisons were more common among trials without industry funding (17% vs. 8%, p=0.04). Trials with industry funding differed from non-industry trials in terms of the drugs studied and the comparators selected. For 73% (61/84) of drugs and 90% (19/21) of unique comparisons, trials were funded exclusively by either industry or non-industry. We found that industry and non-industry differed when choosing comparators and active drug comparators were rare for both groups. This gap in pediatric research activity limits the evidence available to clinicians treating children and suggests a need to reassess the design and funding of pediatric trials in order to optimize the information derived from pediatric participation in clinical trials. PMID:24376857

The effects of industry sponsorship on comparator selection in trial registrations for neuropsychiatric conditions in children.

PubMed

Dunn, Adam G; Mandl, Kenneth D; Coiera, Enrico; Bourgeois, Florence T

2013-01-01

Pediatric populations continue to be understudied in clinical drug trials despite the increasing use of pharmacotherapy in children, particularly with psychotropic drugs. Most pertinent to the clinical selection of drug interventions are trials directly comparing drugs against other drugs. The aim was to measure the prevalence of active drug comparators in neuropsychiatric drug trials in children and identify the effects of funding source on comparator selection. We analyzed the selection of drugs and drug comparisons in clinical trials registered between January 2006 and May 2012. Completed and ongoing interventional trials examining treatments for six neuropsychiatric conditions in children were included. Networks of drug comparisons for each condition were constructed using information about the trial study arms. Of 421 eligible trial registrations, 228 (63,699 participants) were drug trials addressing ADHD (106 trials), autism spectrum disorders (47), unipolar depression (16), seizure disorders (38), migraines and other headaches (15), or schizophrenia (11). Active drug comparators were used in only 11.0% of drug trials while 44.7% used a placebo control and 44.3% no drug or placebo comparator. Even among conditions with well-established pharmacotherapeutic options, almost all drug interventions were compared to a placebo. Active comparisons were more common among trials without industry funding (17% vs. 8%, p=0.04). Trials with industry funding differed from non-industry trials in terms of the drugs studied and the comparators selected. For 73% (61/84) of drugs and 90% (19/21) of unique comparisons, trials were funded exclusively by either industry or non-industry. We found that industry and non-industry differed when choosing comparators and active drug comparators were rare for both groups. This gap in pediatric research activity limits the evidence available to clinicians treating children and suggests a need to reassess the design and funding of pediatric trials in order to optimize the information derived from pediatric participation in clinical trials.

What learning theories can teach us in designing neurofeedback treatments

PubMed Central

Strehl, Ute

2014-01-01

Popular definitions of neurofeedback point out that neurofeedback is a process of operant conditioning which leads to self-regulation of brain activity. Self-regulation of brain activity is considered to be a skill. The aim of this paper is to clarify that not only operant conditioning plays a role in the acquisition of this skill. In order to design the learning process additional references have to be derived from classical conditioning, two-process-theory and in particular from skill learning and research into motivational aspects. The impact of learning by trial and error, cueing of behavior, feedback, reinforcement, and knowledge of results as well as transfer of self-regulation skills into everyday life will be analyzed in this paper. In addition to these learning theory basics this paper tries to summarize the knowledge about acquisition of self-regulation from neurofeedback studies with a main emphasis on clinical populations. As a conclusion it is hypothesized that learning to self-regulate has to be offered in a psychotherapeutic, i.e., behavior therapy framework. PMID:25414659

What learning theories can teach us in designing neurofeedback treatments.

PubMed

Strehl, Ute

2014-01-01

Popular definitions of neurofeedback point out that neurofeedback is a process of operant conditioning which leads to self-regulation of brain activity. Self-regulation of brain activity is considered to be a skill. The aim of this paper is to clarify that not only operant conditioning plays a role in the acquisition of this skill. In order to design the learning process additional references have to be derived from classical conditioning, two-process-theory and in particular from skill learning and research into motivational aspects. The impact of learning by trial and error, cueing of behavior, feedback, reinforcement, and knowledge of results as well as transfer of self-regulation skills into everyday life will be analyzed in this paper. In addition to these learning theory basics this paper tries to summarize the knowledge about acquisition of self-regulation from neurofeedback studies with a main emphasis on clinical populations. As a conclusion it is hypothesized that learning to self-regulate has to be offered in a psychotherapeutic, i.e., behavior therapy framework.

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

Analysis of originating ultra-short optical dissipative solitary pulses in the actively mode-locked semiconductor heterolasers with an external fiber cavity

NASA Astrophysics Data System (ADS)

Shcherbakov, Alexandre S.; Campos Acosta, Joaquin; Pons Aglio, Alicia; Moreno Zarate, Pedro; Mansurova, Svetlana

2010-06-01

We present an advanced approach to describing low-power trains of bright picosecond optical dissipative solitary pulses with an internal frequency modulation in practically important case of exploiting semiconductor heterolaser operating in near-infrared range in the active mode-locking regime. In the chosen schematic arrangement, process of the active mode-locking is caused by a hybrid nonlinear cavity consisting of this heterolaser and an external rather long single-mode optical fiber exhibiting square-law dispersion, cubic Kerr nonlinearity, and small linear optical losses. Our analysis of shaping dissipative solitary pulses includes three principal contributions associated with the modulated gain, total optical losses, as well as with linear and nonlinear phase shifts. In fact, various trains of the non-interacting to one another optical dissipative solitons appear within simultaneous balance between the second-order dispersion and cubic-law Kerr nonlinearity as well as between active medium gain and linear optical losses in a hybrid cavity. Our specific approach makes possible taking the modulating signals providing non-conventional composite regimes of a multi-pulse active mode-locking. Within our model, a contribution of the appearing nonlinear Ginzburg-Landau operator to the parameters of dissipative solitary pulses is described via exploiting an approximate variational procedure involving the technique of trial functions.

Peri-incisional and intraperitoneal ropivacaine administration: a new effective tool in pain control after laparoscopic surgery in gynecology: a randomized controlled clinical trial.

PubMed

Saccardi, Carlo; Gizzo, Salvatore; Vitagliano, Amerigo; Noventa, Marco; Micaglio, Massimo; Parotto, Matteo; Fiorese, Mauro; Litta, Pietro

2016-12-01

A proportion of patients undergoing laparoscopic gynecological surgery experiences excessive post-operative pain, which results in high rescue analgesic treatment and prolonged hospitalization. The aim of our study was to evaluate the efficacy of intraoperative topical ropivacaine in the control of post-operative pain in the first 48 h after operative laparoscopy for benign adnexal or uterine pathologies . We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial. Patients received a standard dose of topical ropivacaine (injected at the three portal sites and atomized in the abdominal cavity) or placebo. The primary outcome was the evaluation of post-operative pain intensity 6 h after surgery. Secondary outcomes included the intensity of pain during the 48 h after surgery, shoulder tip pain and the request for rescue analgesics during the first 48 h after surgery, time to discharge from recovery room, time to mobilizing on the ward and time to return to daily activities. Patients were divided in two groups (Group_A: benign adnexal pathologies; Group_B: benign uterine diseases) and assigned to Subgroup_1 (receiving ropivacaine) and Subgroup_2 (receiving placebo). A total of 187 women were included: 93 in Group_A and 94 in Group_B. Forty-seven patients entered Subgroup_A1, 46 Subgroup_A2, 48 Subgroup_B1 and 46 Subgroup_B2. Subgroup_A1 experienced lower post-operative pain at 4 (p = 0.008) and 6 h (p = 0.001) as well as a faster return to daily activities (p = 0.01) in comparison with Subgroup_A2. Both Subgroup_A1 and Subgroup_B1 showed lower shoulder tip pain (respectively, p = 0.032 and p = 0.001) as well as shorter time to mobilizing on the ward after surgery (respectively, p = 0.001 and p = 0.01). The remaining variables analysis did not show significant results. Combined topical analgesia with ropivacaine could represent a new safe and effective tool in the control of post-operative pain in gynecological laparoscopic surgery. Given the greater benefits for adnexal surgery, this strategy may be more suitable for this class of patients.

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

PubMed

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

2002-01-01

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

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

PubMed

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

2007-07-18

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

Improvement of Information Transfer Rates Using a Hybrid EEG-NIRS Brain-Computer Interface with a Short Trial Length: Offline and Pseudo-Online Analyses.

PubMed

Shin, Jaeyoung; Kim, Do-Won; Müller, Klaus-Robert; Hwang, Han-Jeong

2018-06-05

Electroencephalography (EEG) and near-infrared spectroscopy (NIRS) are non-invasive neuroimaging methods that record the electrical and metabolic activity of the brain, respectively. Hybrid EEG-NIRS brain-computer interfaces (hBCIs) that use complementary EEG and NIRS information to enhance BCI performance have recently emerged to overcome the limitations of existing unimodal BCIs, such as vulnerability to motion artifacts for EEG-BCI or low temporal resolution for NIRS-BCI. However, with respect to NIRS-BCI, in order to fully induce a task-related brain activation, a relatively long trial length (≥10 s) is selected owing to the inherent hemodynamic delay that lowers the information transfer rate (ITR; bits/min). To alleviate the ITR degradation, we propose a more practical hBCI operated by intuitive mental tasks, such as mental arithmetic (MA) and word chain (WC) tasks, performed within a short trial length (5 s). In addition, the suitability of the WC as a BCI task was assessed, which has so far rarely been used in the BCI field. In this experiment, EEG and NIRS data were simultaneously recorded while participants performed MA and WC tasks without preliminary training and remained relaxed (baseline; BL). Each task was performed for 5 s, which was a shorter time than previous hBCI studies. Subsequently, a classification was performed to discriminate MA-related or WC-related brain activations from BL-related activations. By using hBCI in the offline/pseudo-online analyses, average classification accuracies of 90.0 ± 7.1/85.5 ± 8.1% and 85.8 ± 8.6/79.5 ± 13.4% for MA vs. BL and WC vs. BL, respectively, were achieved. These were significantly higher than those of the unimodal EEG- or NIRS-BCI in most cases. Given the short trial length and improved classification accuracy, the average ITRs were improved by more than 96.6% for MA vs. BL and 87.1% for WC vs. BL, respectively, compared to those reported in previous studies. The suitability of implementing a more practical hBCI based on intuitive mental tasks without preliminary training and with a shorter trial length was validated when compared to previous studies.

Non-pharmacological interventions for assisting the induction of anaesthesia in children.

PubMed

Manyande, Anne; Cyna, Allan M; Yip, Peggy; Chooi, Cheryl; Middleton, Philippa

2015-07-14

Induction of general anaesthesia can be distressing for children. Non-pharmacological methods for reducing anxiety and improving co-operation may avoid the adverse effects of preoperative sedation. To assess the effects of non-pharmacological interventions in assisting induction of anaesthesia in children by reducing their anxiety, distress or increasing their co-operation. In this updated review we searched CENTRAL (the Cochrane Library 2012, Issue 12) and searched the following databases from inception to 15 January 2013: MEDLINE, EMBASE, PsycINFO and Web of Science. We reran the search in August 2014. We will deal with the single study found to be of interest when we next update the review. We included randomized controlled trials of a non-pharmacological intervention implemented on the day of surgery or anaesthesia. At least two review authors independently extracted data and assessed risk of bias in trials. We included 28 trials (2681 children) investigating 17 interventions of interest; all trials were conducted in high-income countries. Overall we judged the trials to be at high risk of bias. Except for parental acupuncture (graded low), all other GRADE assessments of the primary outcomes of comparisons were very low, indicating a high degree of uncertainty about the overall findings. Parental presence: In five trials (557 children), parental presence at induction of anaesthesia did not reduce child anxiety compared with not having a parent present (standardized mean difference (SMD) 0.03, 95% confidence interval (CI) -0.14 to 0.20). In a further three trials (267 children) where we were unable to pool results, we found no clear differences in child anxiety, whether a parent was present or not. In a single trial, child anxiety showed no significant difference whether one or two parents were present, although parental anxiety was significantly reduced when both parents were present at the induction. Parental presence was significantly less effective than sedative premedication in reducing children's anxiety at induction in three trials with 254 children (we could not pool results). Child interventions (passive): When a video of the child's choice was played during induction, children were significantly less anxious than controls (median difference modified Yale Preoperative Anxiety Scale (mYPAS) 31.2, 95% CI 27.1 to 33.3) in a trial of 91 children. In another trial of 120 children, co-operation at induction did not differ significantly when a video fairytale was played before induction. Children exposed to low sensory stimulation were significantly less anxious than control children on introduction of the anaesthesia mask and more likely to be co-operative during induction in one trial of 70 children. Music therapy did not show a significant effect on children's anxiety in another trial of 51 children. Child interventions (mask introduction): We found no significant differences between a mask exposure intervention and control in a single trial of 103 children for child anxiety (risk ratio (RR) 0.59, 95% CI 0.31 to 1.11) although children did demonstrate significantly better co-operation in the mask exposure group (RR 1.27, 95% CI 1.06 to 1.51). Child interventions (interactive): In a three-arm trial of 168 children, preparation with interactive computer packages (in addition to parental presence) was more effective than verbal preparation, although differences between computer and cartoon preparation were not significant, and neither was cartoon preparation when compared with verbal preparation. Children given video games before induction were significantly less anxious at induction than those in the control group (mYPAS mean difference (MD) -9.80, 95% CI -19.42 to -0.18) and also when compared with children who were sedated with midazolam (mYPAS MD -12.20, 95% CI -21.82 to -2.58) in a trial of 112 children. When compared with parental presence only, clowns or clown doctors significantly lessened children's anxiety in the operating/induction room (mYPAS MD -24.41, 95% CI -38.43 to -10.48; random-effects, I² 75%) in three trials with a total of 133 children. However, we saw no significant differences in child anxiety in the operating room between clowns/clown doctors and sedative premedication (mYPAS MD -9.67, 95% CI -21.14 to 1.80, random-effects, I² 66%; 2 trials of 93 children). In a trial of hypnotherapy versus sedative premedication in 50 children, there were no significant differences in children's anxiety at induction (RR 0.59, 95% CI 0.33 to 1.04). Parental interventions: Children of parents having acupuncture compared with parental sham acupuncture were less anxious during induction (mYPAS MD -17, 95% CI -30.51 to -3.49) and were more co-operative (RR 1.59, 95% CI 1.01 to 2.53) in a single trial of 67 children. Two trials with 191 parents assessed the effects of parental video viewing but did not report any of the review's prespecified primary outcomes. This review shows that the presence of parents during induction of general anaesthesia does not diminish their child's anxiety. Potentially promising non-pharmacological interventions such as parental acupuncture; clowns/clown doctors; playing videos of the child's choice during induction; low sensory stimulation; and hand-held video games need further investigation in larger studies.

Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study: design of a randomized controlled trial.

PubMed

van Vulpen, Jonna K; Siersema, Peter D; van Hillegersberg, Richard; Nieuwenhuijzen, Grard A P; Kouwenhoven, Ewout A; Groenendijk, Richard P R; van der Peet, Donald L; Hazebroek, Eric J; Rosman, Camiel; Schippers, Carlo C G; Steenhagen, Elles; Peeters, Petra H M; May, Anne M

2017-08-18

Following esophagectomy, esophageal cancer patients experience a clinically relevant deterioration of health-related quality of life, both on the short- and long-term. With the currently growing number of esophageal cancer survivors, the burden of disease- and treatment-related complaints and symptoms becomes more relevant. This emphasizes the need for interventions aimed at improving quality of life. Beneficial effects of post-operative physical exercise have been reported in several cancer types, but so far comparable evidence in esophageal cancer patients is lacking. The aim of this study is to investigate effects of physical exercise on health-related quality of life in esophageal cancer patients following surgery. The Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study is a multicenter randomized controlled trial including 150 esophageal cancer patients after surgery with curative intent. Patients are randomly allocated to an exercise group or usual care group. The exercise group participates in a 12-week combined aerobic and resistance exercise program, supervised by a physiotherapist near the patient's home-address. In addition, participants in the exercise group are requested to be physically active for at least 30 min per day, every day of the week. Participants allocated to the usual care group are asked to maintain their habitual physical activity pattern. The primary outcome is health-related quality of life (EORTC-QLQ-C30). Secondary outcomes include esophageal cancer specific quality of life, fatigue, anxiety and depression, sleep quality, work-related factors, cardiorespiratory fitness (VO 2peak ), muscle strength, physical activity, malnutrition risk, anthropometry, blood markers, recurrence of disease and survival. All questionnaire outcomes, diaries and accelerometers are assessed at baseline, post-intervention (12 weeks post-baseline) and 24 weeks post-baseline. Physical fitness, anthropometry and blood markers are assessed at baseline and post-intervention. In addition, adherence and safety are monitored throughout the exercise program. This randomized controlled trial investigates effects of physical exercise versus usual care in esophageal cancer patients after surgery. As the design of the exercise program closely resembles daily practice, this study can contribute both to evidence on effects of exercise in esophageal cancer patients, and to potential implementation strategies. Trial registration:Netherlands Trial Registry NTR5045 Date of trial registration: January 19th, 2015 Date and version study protocol: February 2017, version 1.

Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery.

PubMed

Hemmes, Sabrine N T; Severgnini, Paolo; Jaber, Samir; Canet, Jaume; Wrigge, Hermann; Hiesmayr, Michael; Tschernko, Edda M; Hollmann, Markus W; Binnekade, Jan M; Hedenstierna, Göran; Putensen, Christian; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J

2011-05-06

Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP) and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery. The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO") trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH(2)O with recruitment maneuvers (the lung-protective strategy) or mechanical ventilation with the level of PEEP at maximum 2 cmH(2)O without recruitment maneuvers (the conventional strategy). The primary endpoint is any post-operative pulmonary complication. The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications. ISRCTN: ISRCTN70332574.

Early mobilization of patients who have had a hip or knee joint replacement reduces length of stay in hospital: a systematic review.

PubMed

Guerra, Mark L; Singh, Parminder J; Taylor, Nicholas F

2015-09-01

To systematically review the effect of early mobilization after hip or knee joint replacement surgery on length of stay in an acute hospital. Randomized controlled trials were selected from electronic databases based on inclusion criterion requiring an experimental group mobilizing (sitting out of bed/walking) earlier than a comparison group post joint replacement surgery of the hip or knee in an acute hospital. Clinically homogeneous data were analyzed with meta-analysis. Five randomized controlled trials (totaling 622 participants) were included for review. A meta-analysis of 5 trials found a reduced length of stay of 1.8 days (95% confidence interval 1.1 to 2.6) in favor of the experimental group. In 4 of the 5 trials the experimental group first sat out of bed within 24 hours post operatively. In 4 of the 5 trials the experimental group first walked within 48 hours post operatively. Individual trials reported benefits in range of motion, muscle strength and health-related quality of life in favor of the experimental group. There were no differences in discharge destinations, incidence of negative outcomes or adverse events attributable to early mobilization when compared to the comparison groups. Early mobilization post hip or knee joint replacement surgery can result in a reduced length of stay of about 1.8 days. Trials that reported these positive results showed that early mobilization can be achieved within 24 hours of operation. This positive gain was achieved without an increase in negative outcomes. © The Author(s) 2014.

An approach to combining parallel and cross-over trials with and without run-in periods using individual patient data.

PubMed

Tvete, Ingunn F; Olsen, Inge C; Fagerland, Morten W; Meland, Nils; Aldrin, Magne; Smerud, Knut T; Holden, Lars

2012-04-01

In active run-in trials, where patients may be excluded after a run-in period based on their response to the treatment, it is implicitly assumed that patients have individual treatment effects. If individual patient data are available, active run-in trials can be modelled using patient-specific random effects. With more than one trial on the same medication available, one can obtain a more precise overall treatment effect estimate. We present a model for joint analysis of a two-sequence, four-period cross-over trial (AABB/BBAA) and a three-sequence, two-period active run-in trial (AB/AA/A), where the aim is to investigate the effect of a new treatment for patients with pain due to osteoarthritis. Our approach enables us to separately estimate the direct treatment effect for all patients, for the patients excluded after the active run-in trial prior to randomisation, and for the patients who completed the active run-in trial. A similar model approach can be used to analyse other types of run-in trials, but this depends on the data and type of other trials available. We assume equality of the various carry-over effects over time. The proposed approach is flexible and can be modified to handle other designs. Our results should be encouraging for those responsible for planning cost-efficient clinical development programmes.

Stimulus- and response-reinforcer contingencies in autoshaping, operant, classical, and omission training procedures in rats.

PubMed

Atnip, G W

1977-07-01

Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning (responding was necessary for food delivery); and classical conditioning (food followed lever presentations regardless of responding). Each group then received 500 trials on an omission procedure in which food was omitted on trials with a response. Another group received 1000 trials on the omission procedure, and a fifth group, random control, received 1000 uncorrelated presentations of lever and food. The autoshaping, operant, and classical groups reached high response levels by the end of initial training. Acquisition was fastest in the autoshaping group. Responding remained consistently low in the control group. The omission group responded at a level between the control group and the other three groups. During omission training, responding in these three groups declined to the omission-group level. During omission training, the rats continued contacting the lever frequently after lever pressing had declined. Response maintenance under omission training seems not to require topographic similarity between the response and reinforcer-elicited consummatory behaviors.

Stimulus- and response-reinforcer contingencies in autoshaping, operant, classical, and omission training procedures in rats

PubMed Central

Atnip, Gilbert W.

1977-01-01

Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning (responding was necessary for food delivery); and classical conditioning (food followed lever presentations regardless of responding). Each group then received 500 trials on an omission procedure in which food was omitted on trials with a response. Another group received 1000 trials on the omission procedure, and a fifth group, random control, received 1000 uncorrelated presentations of lever and food. The autoshaping, operant, and classical groups reached high response levels by the end of initial training. Acquisition was fastest in the autoshaping group. Responding remained consistently low in the control group. The omission group responded at a level between the control group and the other three groups. During omission training, responding in these three groups declined to the omission-group level. During omission training, the rats continued contacting the lever frequently after lever pressing had declined. Response maintenance under omission training seems not to require topographic similarity between the response and reinforcer-elicited consummatory behaviors. PMID:16812014

Long-term effects of operating temperature and sulphate addition on the methanogenic community structure of anaerobic hybrid reactors.

PubMed

Pender, Seán; Toomey, Margaret; Carton, Micheál; Eardly, Dónal; Patching, John W; Colleran, Emer; O'Flaherty, Vincent

2004-02-01

The diversity, population dynamics, and activity profiles of methanogens in anaerobic granular sludges from two anaerobic hybrid reactors treating a molasses wastewater both mesophilically (37 degrees C) and thermophilically (55 degrees C) during a 1081 day trial were determined. The influent to one of the reactors was supplemented with sulphate, after an acclimation period of 112 days, to determine the effect of competition with sulphate-reducing bacteria on the methanogenic community structure. Sludge samples were removed from the reactors at intervals throughout the operational period and examined by amplified ribosomal DNA (rDNA) restriction analysis (ARDRA) and partial sequencing of 16S rRNA genes. In total, 18 operational taxonomic units (OTUs) were identified, 12 of which were sequenced. The methanogenic communities in both reactors changed during the operational period. The seed sludge and the reactor biomass sampled during mesophilic operation, both in the presence and absence of sulphate, was characterised by a predominance of Methanosaeta spp. Following temperature elevation, the dominant methanogenic sequences detected in the non-sulphate supplemented reactor were closely related to Methanocorpusculum parvum. By contrast, the dominant OTUs detected in the sulphate-supplemented reactor upon temperature increase were related to the hydrogen-utilising methanogen, Methanobacterium thermoautotrophicum. The observed methanogenic community structure in the reactors correlated with the operational performance of the reactors during the trial and with physiological measurements of the reactor biomass. Both reactors achieved chemical oxygen demand (COD) removal efficiencies of over 90% during mesophilic operation, with or without sulphate supplementation. During thermophilic operation, the presence of sulphate resulted in decreased reactor performance (effluent acetate concentrations of >3000 mg/l and biogas methane content of <25%). It was demonstrated that methanogenic conversion of acetate at 55 degrees C was extremely sensitive to inhibition by sulphide (50% inhibition at 8-17 mg/l unionised sulphide at pH 7.6-8.0), while the conversion of H(2)/CO(2) methanogenically was favoured. The combination of experiments carried out demonstrated the presence of specific methanogenic populations during periods of successful operational performance.

Application of Incident Command Structure to clinical trial management in the academic setting: principles and lessons learned.

PubMed

Reynolds, Penny S; Michael, Mary J; Spiess, Bruce D

2017-02-09

Clinical trial success depends on appropriate management, but practical guidance to trial organisation and planning is lacking. The Incident Command System (ICS) is the 'gold standard' management system developed for managing diverse operations in major incident and public health arenas. It enables effective and flexible management through integration of personnel, procedures, resources, and communications within a common hierarchical organisational structure. Conventional ICS organisation consists of five function modules: Command, Planning, Operations, Logistics, and Finance/Administration. Large clinical trials will require a separate Regulatory Administrative arm, and an Information arm, consisting of dedicated data management and information technology staff. We applied ICS principles to organisation and management of the Prehospital Use of Plasma in Traumatic Haemorrhage (PUPTH) trial. This trial was a multidepartmental, multiagency, randomised clinical trial investigating prehospital administration of thawed plasma on mortality and coagulation response in severely injured trauma patients. We describe the ICS system as it would apply to large clinical trials in general, and the benefits, barriers, and lessons learned in utilising ICS principles to reorganise and coordinate the PUPTH trial. Without a formal trial management structure, early stages of the trial were characterised by inertia and organisational confusion. Implementing ICS improved organisation, coordination, and communication between multiple agencies and service groups, and greatly streamlined regulatory compliance administration. However, unfamiliarity of clinicians with ICS culture, conflicting resource allocation priorities, and communication bottlenecks were significant barriers. ICS is a flexible and powerful organisational tool for managing large complex clinical trials. However, for successful implementation the cultural, psychological, and social environment of trial participants must be accounted for, and personnel need to be educated in the basics of ICS. ClinicalTrials.gov, NCT02303964 . Registered on 28 November 2014.

Clinical staging and operative reporting for multi-institutional trials in head and neck squamous cell carcinoma.

PubMed

Weymuller, E A

1997-12-01

A Strategic Planning Conference (jointly supported by NCI and NIDCD) was convened to consider potential improvements in surgical patient data for multi-institutional trials. The thesis underlying this project is that inadequacies in staging, pretreatment patient stratification, and the details of surgical resection may have obscured the detection of treatment effect. The goals of this project were multiple: (1) to consider the utility of new clinical stratification variables, (2) to increase the precision of tumor staging, and (3) to improve operative reporting for multi-institutional trials in head and neck cancer. The conference attendees came to a number of important conclusions: (1) TNM status is inadequate for describing head and neck cancer in a multi-institutional trial setting. A detailed anatomic reporting scheme is proposed; (2) comorbidity measures should be included as patient descriptors, especially those that meet the criteria "definitely important and easy to obtain"; (3) surgical reporting in multi-institutional trials should use a format that is compatible with computer analysis and use the same items as the revised (anatomic) staging system; (4) the surgeon should be personally responsible for data coding and should interact directly with the pathologist in marking the surgical specimen; (5) pathologic reporting should use an anatomic template identical to the staging and operative reporting formats.

Harmonization of the Practice of Independent Ethics Committees in Italy: Project E-Submission

PubMed Central

De Feo, Gianfranco; Chiabrando, Giacomo; Cannovo, Nunzia; Galluccio, Antonio; Tomino, Carlo

2012-01-01

Aim The high variability of “centre-specific” documentation required by Independent Ethics Committee (IEC) plays a role in the time required for activation of participating centres of multicentre clinical trials. This study (a) provides a picture of the different activities, structural requirements and resources dedicated to the operation of the local IEC in Italy; (b) defines a detailed list of “centre-specific” documents considered as essential by the IEC for issuing its opinion and (c) suggests a “single document” to reduce the variability of the “centre-specific” documents required by the IEC. Methodology Two surveys were conducted through the portal of National Monitoring Centre of Clinical Trials (https://oss-sper-clin.agenziafarmaco.it/). The first survey focused on the local IEC resources and on the “centre-specific” documentation that local IEC required from the Sponsor and local Principal Investigator (PI). The second focused on “single document” required in the form of statements from the Sponsor and the PI. Answers were discussed and extended during regular scheduled teleconferences and plenary meeting. Principal Findings From 22/07/2009 to 15/12/2009, and from 19/04/2010 to 14/05/2010, 131 and 125 IECs responded to the first and the second surveys, respectively. 67% and 51% of IECs consider the structural requirements and the staff dedicated to the activity of the IECs as sufficient, respectively. Most of the IECs consider the “centre-specific” documentation as necessary for issuing the opinion, and a high percentage of IECs consider the proposed documentation as acceptable in substitution to any other “centre-specific” documentation already in use. Conclusions The harmonization of IECs practice in Italy is the first step to facilitate multicentre clinical trials. Similar efforts should be directed to reduce the total number of IECs and to standardize clinical trials approval procedures, focusing on administrative procedures as well. PMID:23145015

Optimized post-operative surveillance of permanent pacemakers by home monitoring: the OEDIPE trial.

PubMed

Halimi, Franck; Clémenty, Jacques; Attuel, Patrick; Dessenne, Xavier; Amara, Walid

2008-12-01

The OEDIPE trial examined the safety and efficacy of an abbreviated hospitalization after implantation or replacement of dual-chamber pacemakers (PM) using a telecardiology-based ambulatory surveillance programme. Patients were randomly assigned to (i) an active group, discharged from the hospital 24 h after a first PM implant or 4-6 h after replacement, and followed for 4 weeks with Home-Monitoring (HM), or (ii) a control group followed for 4 weeks according to usual medical practices. The primary objective was to confirm that the proportion of patients who experienced one or more major adverse events (MAE) was not higher in the active than in the control group. The study included 379 patients. At least one treatment-related MAE was observed in 9.2% of patients (n = 17) assigned to the active group vs. 13.3% of patients (n = 26) in the control group (P = 0.21), a 4.1% absolute risk reduction (95% CI -2.2 to 10.4; P = 0.98). By study design, the mean hospitalization duration was 34% shorter in the active than in the control group (P < 0.001), and HM facilitated the early detection of technical issues and detectable clinical anomalies. Early discharge with HM after PM implantation or replacement was safe and facilitated the monitoring of patients in the month following the procedure.

Optimized post-operative surveillance of permanent pacemakers by home monitoring: the OEDIPE trial

PubMed Central

Halimi, Franck; Clémenty, Jacques; Attuel, Patrick; Dessenne, Xavier; Amara, Walid

2008-01-01

Aims The ŒDIPE trial examined the safety and efficacy of an abbreviated hospitalization after implantation or replacement of dual-chamber pacemakers (PM) using a telecardiology-based ambulatory surveillance programme. Methods and results Patients were randomly assigned to (i) an active group, discharged from the hospital 24 h after a first PM implant or 4–6 h after replacement, and followed for 4 weeks with Home-Monitoring (HM), or (ii) a control group followed for 4 weeks according to usual medical practices. The primary objective was to confirm that the proportion of patients who experienced one or more major adverse events (MAE) was not higher in the active than in the control group. The study included 379 patients. At least one treatment-related MAE was observed in 9.2% of patients (n = 17) assigned to the active group vs. 13.3% of patients (n = 26) in the control group (P = 0.21), a 4.1% absolute risk reduction (95% CI −2.2 to 10.4; P = 0.98). By study design, the mean hospitalization duration was 34% shorter in the active than in the control group (P < 0.001), and HM facilitated the early detection of technical issues and detectable clinical anomalies. Conclusion Early discharge with HM after PM implantation or replacement was safe and facilitated the monitoring of patients in the month following the procedure. PMID:18775878

Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer's disease.

PubMed

Satlin, Andrew; Wang, Jinping; Logovinsky, Veronika; Berry, Scott; Swanson, Chad; Dhadda, Shobha; Berry, Donald A

2016-01-01

Recent failures in phase 3 clinical trials in Alzheimer's disease (AD) suggest that novel approaches to drug development are urgently needed. Phase 3 risk can be mitigated by ensuring that clinical efficacy is established before initiating confirmatory trials, but traditional phase 2 trials in AD can be lengthy and costly. We designed a Bayesian adaptive phase 2, proof-of-concept trial with a clinical endpoint to evaluate BAN2401, a monoclonal antibody targeting amyloid protofibrils. The study design used dose response and longitudinal modeling. Simulations were used to refine study design features to achieve optimal operating characteristics. The study design includes five active treatment arms plus placebo, a clinical outcome, 12-month primary endpoint, and a maximum sample size of 800. The average overall probability of success is ≥80% when at least one dose shows a treatment effect that would be considered clinically meaningful. Using frequent interim analyses, the randomization ratios are adapted based on the clinical endpoint, and the trial can be stopped for success or futility before full enrollment. Bayesian statistics can enhance the efficiency of analyzing the study data. The adaptive randomization generates more data on doses that appear to be more efficacious, which can improve dose selection for phase 3. The interim analyses permit stopping as soon as a predefined signal is detected, which can accelerate decision making. Both features can reduce the size and duration of the trial. This study design can mitigate some of the risks associated with advancing to phase 3 in the absence of data demonstrating clinical efficacy. Limitations to the approach are discussed.

Blinded sample size re-estimation in three-arm trials with 'gold standard' design.

PubMed

Mütze, Tobias; Friede, Tim

2017-10-15

In this article, we study blinded sample size re-estimation in the 'gold standard' design with internal pilot study for normally distributed outcomes. The 'gold standard' design is a three-arm clinical trial design that includes an active and a placebo control in addition to an experimental treatment. We focus on the absolute margin approach to hypothesis testing in three-arm trials at which the non-inferiority of the experimental treatment and the assay sensitivity are assessed by pairwise comparisons. We compare several blinded sample size re-estimation procedures in a simulation study assessing operating characteristics including power and type I error. We find that sample size re-estimation based on the popular one-sample variance estimator results in overpowered trials. Moreover, sample size re-estimation based on unbiased variance estimators such as the Xing-Ganju variance estimator results in underpowered trials, as it is expected because an overestimation of the variance and thus the sample size is in general required for the re-estimation procedure to eventually meet the target power. To overcome this problem, we propose an inflation factor for the sample size re-estimation with the Xing-Ganju variance estimator and show that this approach results in adequately powered trials. Because of favorable features of the Xing-Ganju variance estimator such as unbiasedness and a distribution independent of the group means, the inflation factor does not depend on the nuisance parameter and, therefore, can be calculated prior to a trial. Moreover, we prove that the sample size re-estimation based on the Xing-Ganju variance estimator does not bias the effect estimate. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Placebo effects in trials evaluating 12 selected minimally invasive interventions: a systematic review and meta-analysis

PubMed Central

Holtedahl, Robin; Brox, Jens Ivar; Tjomsland, Ole

2015-01-01

Objectives To analyse the impact of placebo effects on outcome in trials of selected minimally invasive procedures and to assess reported adverse events in both trial arms. Design A systematic review and meta-analysis. Data sources and study selection We searched MEDLINE and Cochrane library to identify systematic reviews of musculoskeletal, neurological and cardiac conditions published between January 2009 and January 2014 comparing selected minimally invasive with placebo (sham) procedures. We searched MEDLINE for additional randomised controlled trials published between January 2000 and January 2014. Data synthesis Effect sizes (ES) in the active and placebo arms in the trials’ primary and pooled secondary end points were calculated. Linear regression was used to analyse the association between end points in the active and sham groups. Reported adverse events in both trial arms were registered. Results We included 21 trials involving 2519 adult participants. For primary end points, there was a large clinical effect (ES≥0.8) after active treatment in 12 trials and after sham procedures in 11 trials. For secondary end points, 7 and 5 trials showed a large clinical effect. Three trials showed a moderate difference in ES between active treatment and sham on primary end points (ES ≥0.5) but no trials reported a large difference. No trials showed large or moderate differences in ES on pooled secondary end points. Regression analysis of end points in active treatment and sham arms estimated an R2 of 0.78 for primary and 0.84 for secondary end points. Adverse events after sham were in most cases minor and of short duration. Conclusions The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated. PMID:25636794

US Navy Submarine Sea Trial of the NASA Air Quality Monitor

NASA Technical Reports Server (NTRS)

Limero, Thomas; Wallace, William T.; Manney, Joshua A.; Mudgett, Paul D.

2017-01-01

For the past four years, the Air Quality Monitor (AQM) has been the operational instrument for measuring trace volatile organic compounds on the International Space Station (ISS). The key components of the AQM are the inlet preconcentrator, the gas chromatograph (GC), and the differential mobility spectrometer. Most importantly, the AQM operates at atmospheric pressure and uses air as the GC carrier gas, which translates into a small reliable instrument. Onboard ISS there are two AQMs, with different GC columns that detect and quantify 22 compounds. The AQM data contributes valuable information to the assessment of air quality aboard ISS for each crew increment. The U.S. Navy is looking to update its submarine air monitoring suite of instruments, and the success of the AQM on ISS has led to a jointly planned submarine sea trial of a NASA AQM. In addition to the AQM, the Navy is also interested in the Multi-Gas Monitor (MGM), which was successfully flown on ISS as a technology demonstration to measure major constituent gases (oxygen, carbon dioxide, water vapor, and ammonia). A separate paper will present the MGM sea trial results. A prototype AQM, which is virtually identical to the operational AQM, has been readied for the sea trial. Only one AQM will be deployed during the sea trial, but it is sufficient to detect the compounds of interest to the Navy for the purposes of this trial. A significant benefit of the AQM is that runs can be scripted for pre-determined intervals and no crew intervention is required. The data from the sea trial will be compared to archival samples collected prior to and during the trial period. This paper will give a brief overview of the AQM technology and protocols for the submarine trial. After a quick review of the AQM preparation, the main focus of the paper will be on the results of the submarine trial. Of particular interest will be the comparison of the contaminants found in the ISS and submarine atmospheres, as both represent closed environments. In U.K. submarine trials in the early 2000s, the submarine and ISS atmospheres were found to be remarkably similar.

Fast-track surgery after gynaecological oncological surgery: study protocol for a prospective randomised controlled trial.

PubMed

Cui, Ling; Shi, Yu; Zhang, G N

2016-12-15

Fast-track surgery (FTS), also known as enhanced recovery after surgery, is a multidisciplinary approach to accelerate recovery, reduce complications, minimise hospital stay without increasing readmission rates, and reduce health care costs, all without compromising patient safety. The advantages of FTS in abdominal surgery most likely extend to gynaecological surgery, but this is an assumption, as FTS in elective gynaecological surgery has not been well studied. No consensus guidelines have been developed for gynaecological oncological surgery although surgeons have attempted to introduce slightly modified FTS programmes for patients undergoing such surgery. To our knowledge, there are no published randomised controlled trials; however, some studies have shown that FTS in gynaecological oncological surgery leads to early hospital discharge with high levels of patient satisfaction. The aim of this study is whether FTS reduces the length of stay in hospital compared to traditional management. The secondary aim is whether FTS is associated with any increase in post-surgical complications compared to traditional management (for both open and laparoscopic surgery). This trial will prospectively compare FTS and traditional management protocols. The primary endpoint is the length of post-operative hospitalisation (days, mean ± standard deviation), defined as the number of days between the date of discharge and the date of surgery. The secondary endpoints are complications in both groups (FTS versus traditional protocol) occurring during the first 3 months post-operatively including infection (wound infection, lung infection, intraperitoneal infection), post-operative nausea and vomiting, ileus, post-operative haemorrhage, post-operative thrombosis, and the Acute Physiology and Chronic Health Enquiry II score. The advantages of FTS most likely extend to gynaecology, although, to our knowledge, there are no randomised controlled trials. The aim of this study is to compare the post-operative length of hospitalisation after major gynaecological or gynaecological oncological surgery and to analyse patients' post-operative complications. This trial may reveal whether FTS leads to early hospital discharge with few complications after gynaecological surgery. NCT02687412 . Approval Number: SCCHEC20160001. Date of registration: registered on 23 February 2016.

Polymethylmethacrylate bone cements and additives: A review of the literature

PubMed Central

Arora, Manit; Chan, Edward KS; Gupta, Sunil; Diwan, Ashish D

2013-01-01

Polymethylmethacrylate (PMMA) bone cement technology has progressed from industrial Plexiglass administration in the 1950s to the recent advent of nanoparticle additives. Additives have been trialed to address problems with modern bone cements such as the loosening of prosthesis, high post-operative infection rates, and inflammatory reduction in interface integrity. This review aims to assess current additives used in PMMA bone cements and offer an insight regarding future directions for this biomaterial. Low index (< 15%) vitamin E and low index (< 5 g) antibiotic impregnated additives significantly address infection and inflammatory problems, with only modest reductions in mechanical strength. Chitosan (15% w/w PMMA) and silver (1% w/w PMMA) nanoparticles have strong antibacterial activity with no significant reduction in mechanical strength. Future work on PMMA bone cements should focus on trialing combinations of these additives as this may enhance favourable properties. PMID:23610754

Monkey prefrontal neurons during Sternberg task performance: full contents of working memory or most recent item?

PubMed

Konecky, R O; Smith, M A; Olson, C R

2017-06-01

To explore the brain mechanisms underlying multi-item working memory, we monitored the activity of neurons in the dorsolateral prefrontal cortex while macaque monkeys performed spatial and chromatic versions of a Sternberg working-memory task. Each trial required holding three sequentially presented samples in working memory so as to identify a subsequent probe matching one of them. The monkeys were able to recall all three samples at levels well above chance, exhibiting modest load and recency effects. Prefrontal neurons signaled the identity of each sample during the delay period immediately following its presentation. However, as each new sample was presented, the representation of antecedent samples became weak and shifted to an anomalous code. A linear classifier operating on the basis of population activity during the final delay period was able to perform at approximately the level of the monkeys on trials requiring recall of the third sample but showed a falloff in performance on trials requiring recall of the first or second sample much steeper than observed in the monkeys. We conclude that delay-period activity in the prefrontal cortex robustly represented only the most recent item. The monkeys apparently based performance of this classic working-memory task on some storage mechanism in addition to the prefrontal delay-period firing rate. Possibilities include delay-period activity in areas outside the prefrontal cortex and changes within the prefrontal cortex not manifest at the level of the firing rate. NEW & NOTEWORTHY It has long been thought that items held in working memory are encoded by delay-period activity in the dorsolateral prefrontal cortex. Here we describe evidence contrary to that view. In monkeys performing a serial multi-item working memory task, dorsolateral prefrontal neurons encode almost exclusively the identity of the sample presented most recently. Information about earlier samples must be encoded outside the prefrontal cortex or represented within the prefrontal cortex in a cryptic code. Copyright © 2017 the American Physiological Society.

A Preliminary Procedure for Teaching Children with Autism to Mand for Social Information.

PubMed

Shillingsburg, M Alice; Frampton, Sarah E; Wymer, Sarah C; Bartlett, Brittany

2018-03-01

We used procedures established within the mands for information literature to teach two children with autism to mand for social information. Establishing operation trials were alternated with abolishing operation trials to verify the function of the responses as mands. Use of the acquired information was evaluated by examining responding to questions about their social partner. Both participants acquired mands for social information and showed generalization to novel social partners.

Trial of multidisciplinary observation at an expandable sub-marine cabled station "off-hatsushima island observatory" in sagami bay, Japan.

PubMed

Kasaya, Takafumi; Mitsuzawa, Kyohiko; Goto, Tada-Nori; Iwase, Ryoichi; Sayanagi, Keizo; Araki, Eiichiro; Asakawa, Kenichi; Mikada, Hitoshi; Watanabe, Tomoki; Takahashi, Ichiro; Nagao, Toshiyasu

2009-01-01

Sagami Bay is an active tectonic area in Japan. In 1993, a real-time deep sea floor observatory was deployed at 1,175 m depth about 7 km off Hatsushima Island, Sagami Bay to monitor seismic activities and other geophysical phenomena. Video cameras monitored biological activities associated with tectonic activities. The observation system was renovated completely in 2000. An ocean bottom electromagnetic meter (OBEM), an ocean bottom differential pressure gauge (DPG) system, and an ocean bottom gravity meter (OBG) were installed January 2005; operations began in February of that year. An earthquake (M5.4) in April 2006, generated a submarine landslide that reached the Hatsushima Observatory, moving some sensors. The video camera took movies of mudflows; OBEM and other sensors detected distinctive changes occurring with the mudflow. Although the DPG and OBG were recovered in January 2008, the OBEM continues to obtain data.

Effects of virtual reality for stroke individuals based on the International Classification of Functioning and Health: a systematic review.

PubMed

Palma, Gisele Carla Dos Santos; Freitas, Tatiana Beline; Bonuzzi, Giordano Márcio Gatinho; Soares, Marcos Antonio Arlindo; Leite, Paulo Henrique Wong; Mazzini, Natália Araújo; Almeida, Murilo Ruas Groschitz; Pompeu, José Eduardo; Torriani-Pasin, Camila

2017-05-01

This review determines the effects of virtual reality interventions for stroke subjects based on the International Classification of Functioning, Disability,and Health (ICF) framework. Virtual reality is a promising tool for therapy for stroke rehabilitation, but the effects of virtual reality interventions on post-stroke patients based on the specific ICF domains (Body Structures, Body Functions, Activity, and Participation) have not been investigated. A systematic review was conducted, including trials with adults with a clinical diagnosis of a chronic, subacute, or acute stroke. Eligible trials had to include studies with an intervention protocol and follow-up, with a focus on upper limbs and/or lower limbs and/or balance. The Physiotherapy Evidence Database (PEDro) was used to assess the methodological quality of randomized controlled trials. Each trial was separated according to methodological quality into a high-quality trial (PEDro ≥ 6) and a low-quality trial (PEDro ≤ 6). Only high-quality trials were analyzed specifically based on the outcome of these trials. In total, 54 trials involving 1811 participants were included. Of the papers included and considered high quality, 14 trials evaluated areas of the Body Structures component, 20 trials of the Body Functions domain, 17 trials of the Activity component, and 8 trials of the Participation domain. In relation to ICF Part 2, four trials evaluated areas of the Personal Factors component and one trial evaluated domains of the Environmental Factors component. The effects of virtual reality on stroke rehabilitation based on the ICF framework are positive in Body Function and Body Structure. However, the results in the domains Activity and Participation are inconclusive. More high-quality clinical trials are needed to confirm the effectiveness of virtual reality in the domains of Activity and Participation.

Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus.

PubMed

Hemmingsen, Bianca; Gimenez-Perez, Gabriel; Mauricio, Didac; Roqué I Figuls, Marta; Metzendorf, Maria-Inti; Richter, Bernd

2017-12-04

The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether diet, physical activity or both can prevent or delay T2DM and its associated complications in at-risk people is unknown. To assess the effects of diet, physical activity or both on the prevention or delay of T2DM and its associated complications in people at increased risk of developing T2DM. This is an update of the Cochrane Review published in 2008. We searched the CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, ICTRP Search Portal and reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was January 2017. We continuously used a MEDLINE email alert service to identify newly published studies using the same search strategy as described for MEDLINE up to September 2017. We included randomised controlled trials (RCTs) with a duration of two years or more. We used standard Cochrane methodology for data collection and analysis. We assessed the overall quality of the evidence using GRADE. We included 12 RCTs randomising 5238 people. One trial contributed 41% of all participants. The duration of the interventions varied from two to six years. We judged none of the included trials at low risk of bias for all 'Risk of bias' domains.Eleven trials compared diet plus physical activity with standard or no treatment. Nine RCTs included participants with impaired glucose tolerance (IGT), one RCT included participants with IGT, impaired fasting blood glucose (IFG) or both, and one RCT included people with fasting glucose levels between 5.3 to 6.9 mmol/L. A total of 12 deaths occurred in 2049 participants in the diet plus physical activity groups compared with 10 in 2050 participants in the comparator groups (RR 1.12, 95% CI 0.50 to 2.50; 95% prediction interval 0.44 to 2.88; 4099 participants, 10 trials; very low-quality evidence). The definition of T2DM incidence varied among the included trials. Altogether 315 of 2122 diet plus physical activity participants (14.8%) developed T2DM compared with 614 of 2389 comparator participants (25.7%) (RR 0.57, 95% CI 0.50 to 0.64; 95% prediction interval 0.50 to 0.65; 4511 participants, 11 trials; moderate-quality evidence). Two trials reported serious adverse events. In one trial no adverse events occurred. In the other trial one of 51 diet plus physical activity participants compared with none of 51 comparator participants experienced a serious adverse event (low-quality evidence). Cardiovascular mortality was rarely reported (four of 1626 diet plus physical activity participants and four of 1637 comparator participants (the RR ranged between 0.94 and 3.16; 3263 participants, 7 trials; very low-quality evidence). Only one trial reported that no non-fatal myocardial infarction or non-fatal stroke had occurred (low-quality evidence). Two trials reported that none of the participants had experienced hypoglycaemia. One trial investigated health-related quality of life in 2144 participants and noted that a minimal important difference between intervention groups was not reached (very low-quality evidence). Three trials evaluated costs of the interventions in 2755 participants. The largest trial of these reported an analysis of costs from the health system perspective and society perspective reflecting USD 31,500 and USD 51,600 per quality-adjusted life year (QALY) with diet plus physical activity, respectively (low-quality evidence). There were no data on blindness or end-stage renal disease.One trial compared a diet-only intervention with a physical-activity intervention or standard treatment. The participants had IGT. Three of 130 participants in the diet group compared with none of the 141 participants in the physical activity group died (very low-quality evidence). None of the participants died because of cardiovascular disease (very low-quality evidence). Altogether 57 of 130 diet participants (43.8%) compared with 58 of 141 physical activity participants (41.1%) group developed T2DM (very low-quality evidence). No adverse events were recorded (very low-quality evidence). There were no data on non-fatal myocardial infarction, non-fatal stroke, blindness, end-stage renal disease, health-related quality of life or socioeconomic effects.Two trials compared physical activity with standard treatment in 397 participants. One trial included participants with IGT, the other trial included participants with IGT, IFG or both. One trial reported that none of the 141 physical activity participants compared with three of 133 control participants died. The other trial reported that three of 84 physical activity participants and one of 39 control participants died (very low-quality evidence). In one trial T2DM developed in 58 of 141 physical activity participants (41.1%) compared with 90 of 133 control participants (67.7%). In the other trial 10 of 84 physical activity participants (11.9%) compared with seven of 39 control participants (18%) developed T2DM (very low-quality evidence). Serious adverse events were rarely reported (one trial noted no events, one trial described events in three of 66 physical activity participants compared with one of 39 control participants - very low-quality evidence). Only one trial reported on cardiovascular mortality (none of 274 participants died - very low-quality evidence). Non-fatal myocardial infarction or stroke were rarely observed in the one trial randomising 123 participants (very low-quality evidence). One trial reported that none of the participants in the trial experienced hypoglycaemia. One trial investigating health-related quality of life in 123 participants showed no substantial differences between intervention groups (very low-quality evidence). There were no data on blindness or socioeconomic effects. There is no firm evidence that diet alone or physical activity alone compared to standard treatment influences the risk of T2DM and especially its associated complications in people at increased risk of developing T2DM. However, diet plus physical activity reduces or delays the incidence of T2DM in people with IGT. Data are lacking for the effect of diet plus physical activity for people with intermediate hyperglycaemia defined by other glycaemic variables. Most RCTs did not investigate patient-important outcomes.

Validation of post-operative residual contrast enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma.

PubMed

Ellingson, Benjamin M; Abrey, Lauren E; Nelson, Sarah J; Kaufmann, Timothy J; Garcia, Josep; Chinot, Olivier; Saran, Frank; Nishikawa, Ryo; Henriksson, Roger; Mason, Warren P; Wick, Wolfgang; Butowski, Nicholas; Ligon, Keith L; Gerstner, Elizabeth R; Colman, Howard; de Groot, John; Chang, Susan; Mellinghoff, Ingo; Young, Robert J; Alexander, Brian M; Colen, Rivka; Taylor, Jennie W; Arrillaga-Romany, Isabel; Mehta, Arnav; Huang, Raymond Y; Pope, Whitney B; Reardon, David; Batchelor, Tracy; Prados, Michael; Galanis, Evanthia; Wen, Patrick Y; Cloughesy, Timothy F

2018-04-05

In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS). Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2). Post-surgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, MGMT status, and residual tumor volume on OS. A log-linear relationship was observed between post-operative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Post-operative tumor volume is a prognostic factor for OS (P<0.01), regardless of therapy, age, and MGMT promoter methylation status. Post-surgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed glioblastoma treated with chemoradiation with or without concomitant experimental therapy.

Carbon Dioxide-Based versus Saline Tissue Expansion for Breast Reconstruction: Results of the XPAND Prospective, Randomized Clinical Trial.

PubMed

Ascherman, Jeffrey A; Zeidler, Kamakshi; Morrison, Kerry A; Appel, James Z; Berkowitz, R L; Castle, John; Colwell, Amy; Chun, Yoon; Johnson, Debra; Mohebali, Khashayar

2016-12-01

AeroForm is a new type of remote-controlled, needle-free, carbon dioxide-based expander involving a potentially faster method of tissue expansion. Results are presented here from the AirXpanders Patient Activated Controlled Tissue Expander pivotal trial comparing AeroForm to saline tissue expanders. Women undergoing two-stage breast reconstruction were randomized at 17 U.S. sites in this U.S. Food and Drug Administration-approved investigational device exemption trial. Expansion in the investigational arm was performed by the patient in 10-cc increments up to 30 cc/day of carbon dioxide and in the control arm by the physician with periodic bolus injections of saline. Safety endpoints, expansion and reconstruction times, pain, and satisfaction were assessed. One hundred fifty women were treated: 98 with carbon dioxide expanders (n = 168) and 52 with saline expanders (n = 88). The treatment success rate (all breasts exchanged successfully excluding non-device-related failures) was 96.1 percent for carbon dioxide and 98.8 percent for saline. Median time to full expansion and completion of the second-stage operation was 21.0 and 108.5 days (carbon dioxide) versus 46.0 and 136.5 days (saline), respectively, with a similar rate of overall complications. Ease of use for the carbon dioxide expander was rated high by patients (98 percent) and physicians (90 percent). The AirXpanders Patient Activated Controlled Tissue Expander trial results demonstrate that a carbon dioxide-based expander is an effective method of tissue expansion with a similar overall adverse event rate compared to saline expanders, and provides a more convenient and expedient expansion. Therapeutic, I.

National ethics guidance in Sub-Saharan Africa on the collection and use of human biological specimens: a systematic review.

PubMed

Barchi, Francis; Little, Madison T

2016-10-22

Ethical and regulatory guidance on the collection and use of human biospecimens (HBS) for research forms an essential component of national health systems in Sub-Saharan Africa (SSA), where rapid advances in genetic- and genomic-based technologies are fueling clinical trials involving HBS and the establishment of large-scale biobanks. An extensive multi-level search for publicly available ethics regulatory guidance was conducted for each SSA country. A second review documented active trials listed in the WHO International Clinical Trials Registry Platform as of January 2015 in which HBS collection was specified in the protocol. Findings were combined to determine the extent to which countries that are study sites for HBS-related research are supported by regulatory guidance language on the collection, use, ownership and storage of biospecimens. Of the 49 SSA countries, 29 had some form of national ethics guidance, yet only 17 provided language relating to HBS-related research, with specific guidance on consent (14), ownership (6), reuse (10), storage (9), and export/import/transfer (13). Ten countries accounted for 84 % of the active clinical trials involving the collection of HBS in SSA. All except one of these countries were found to have some national guidance in the form of regulations, codes of ethics, and/or standard operating procedures; however, only seven of the ten offered any language specific to HBS. Despite the fact that the bulk of registered clinical trials in SSA involving HBS, as well as existing and proposed sites for biorepositories under the H3Africa Initiative, are currently situated in countries with the most complete ethics and regulatory guidance, variability in the regulations themselves may create challenges for planned and future pan-African collaborations and may require legislative action at the national level to revise. Countries in SSA that still lack regulatory guidance on HBS will require extensive health system strengthening in ethics governance before they can be full participants in the modern research enterprise.

DeLLITE Depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial

PubMed Central

Kerse, Ngaire; Falloon, Karen; Moyes, Simon A; Hayman, Karen J; Dowell, Tony; Kolt, Gregory S; Elley, C Raina; Hatcher, Simon; Peri, Kathy; Keeling, Sally; Robinson, Elizabeth; Parsons, John; Wiles, Janine; Arroll, Bruce

2008-01-01

Background Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. Methods/design The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report). Discussion Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Trial registration Australian and New Zealand Clinical Trials Register ACTRN12605000475640 PMID:18501008

Temporal Trends and Predictors for Cancer Clinical Trial Availability for Medically Underserved Populations

PubMed Central

Lakoduk, Ashley M.; Priddy, Laurin L.; Yan, Jingsheng; Xie, Xian-Jin

2015-01-01

Background. Lack of access to available cancer clinical trials has been cited as a key factor limiting trial accrual, particularly among medically underserved populations. We examined the trends and factors in clinical trial availability within a major U.S. safety-net hospital system. Materials and Methods. We identified cancer clinical trials activated at the Harold C. Simmons Cancer from 1991 to 2014 and recorded the characteristics of the trials that were and were not activated at the Parkland Health and Hospital System satellite site. We used univariate and multivariate logistic regression to determine the association between trial characteristics and nonactivation status, and chi-square analysis to determine the association between the trial characteristics and the reasons for nonactivation. Results. A total of 773 trials were identified, of which 152 (20%) were not activated at Parkland. In multivariable analysis, nonactivation at Parkland was associated with trial year, sponsor, and phase. Compared with the 1991–2006 period, clinical trials in the 2007–2014 period were almost eightfold more likely not to be activated at Parkland. The most common reasons for nonactivation at Parkland were an inability to perform the study procedures (27%) and the startup costs (15%). Conclusion. Over time, in this single-center setting, a decreasing proportion of cancer clinical trials were available to underserved populations. Trial complexity and costs appeared to account for much of this trend. Efforts to overcome these barriers will be key to equitable access to clinical trials, efficient accrual, and the generalizability of the results. Implications for Practice: Despite numerous calls to increase and diversify cancer clinical trial accrual, the present study found that cancer clinical trial activation rates in a safety-net setting for medically underserved populations have decreased substantially in recent years. The principal reasons for study nonactivation were expenses and an inability to perform the study-related procedures, reflecting the increasing costs and complexity of cancer clinical trials. Future efforts need to focus on strategies to mitigate the increasing disparity in access to clinical research and cutting-edge therapies, which also threatens to hinder study accrual, completion rates, and generalizability. PMID:26018661

Sensor supported pilot assistance for helicopter flight in DVE

NASA Astrophysics Data System (ADS)

Waanders, Tim; Münsterer, T.; Kress, M.

2013-05-01

Helicopter operations at low altitude are to this day only performed under VFR conditions in which safe piloting of the aircraft relies on the pilot's visual perception of the outside environment. However, there are situations in which a deterioration of visibility conditions may cause the pilot to lose important visual cues thereby increasing workload and compromising flight safety and mission effectiveness. This paper reports on a pilot assistance system for all phases of flight which is intended to: • Provide navigational support and mission management • Support landings/take-offs in unknown environment and in DVE • Enhance situational awareness in DVE • Provide obstacle and terrain surface detection and warning • Provide upload, sensor based update and download of database information for debriefing and later missions. The system comprises a digital terrain and obstacle database, tactical information, flight plan management combined with an active 3D sensor enabling the above mentioned functionalities. To support pilots during operations in DVE, an intuitive 3D/2D cueing through both head-up and head-down means is proposed to retain situational awareness. This paper further describes the system concept and will elaborate on results of simulator trials in which the functionality was evaluated by operational pilots in realistic and demanding scenarios such as a SAR mission to be performed in mountainous area under different visual conditions. The objective of the simulator trials was to evaluate the functional integration and HMI definition for the NH90 Tactical Transport Helicopter.

Qualitative research within trials: developing a standard operating procedure for a clinical trials unit

PubMed Central

2013-01-01

Background Qualitative research methods are increasingly used within clinical trials to address broader research questions than can be addressed by quantitative methods alone. These methods enable health professionals, service users, and other stakeholders to contribute their views and experiences to evaluation of healthcare treatments, interventions, or policies, and influence the design of trials. Qualitative data often contribute information that is better able to reform policy or influence design. Methods Health services researchers, including trialists, clinicians, and qualitative researchers, worked collaboratively to develop a comprehensive portfolio of standard operating procedures (SOPs) for the West Wales Organisation for Rigorous Trials in Health (WWORTH), a clinical trials unit (CTU) at Swansea University, which has recently achieved registration with the UK Clinical Research Collaboration (UKCRC). Although the UKCRC requires a total of 25 SOPs from registered CTUs, WWORTH chose to add an additional qualitative-methods SOP (QM-SOP). Results The qualitative methods SOP (QM-SOP) defines good practice in designing and implementing qualitative components of trials, while allowing flexibility of approach and method. Its basic principles are that: qualitative researchers should be contributors from the start of trials with qualitative potential; the qualitative component should have clear aims; and the main study publication should report on the qualitative component. Conclusions We recommend that CTUs consider developing a QM-SOP to enhance the conduct of quantitative trials by adding qualitative data and analysis. We judge that this improves the value of quantitative trials, and contributes to the future development of multi-method trials. PMID:23433341

Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion.

PubMed

Carless, Paul A; Rubens, Fraser D; Anthony, Danielle M; O'Connell, Dianne; Henry, David A

2011-03-16

Concerns regarding the safety of transfused blood have generated considerable enthusiasm for the use of technologies intended to reduce the use of allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis (PRP) offers an alternative approach to blood conservation. To examine the evidence for the efficacy of PRP in reducing peri-operative allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on clinical outcomes such as mortality and re-operation rates. We identified studies by searching MEDLINE (1950 to 2009), EMBASE (1980 to 2009), The Cochrane Library (Issue 1, 2009), the Internet (to March 2009) and the reference lists of published articles, reports, and reviews. Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to PRP, or to a control group which did not receive the intervention. Primary outcomes measured were: the number of patients exposed to allogeneic RBC transfusion, and the amount of RBC transfused. Other outcomes measured were: the number of patients exposed to allogeneic platelet transfusions, fresh frozen plasma, and cryoprecipitate, blood loss, re-operation for bleeding, post-operative complications (thrombosis), mortality, and length of hospital stay. Treatment effects were pooled using a random-effects model. Trial quality was assessed using criteria proposed by Schulz et al (Schulz 1995). Twenty-two trials of PRP were identified that reported data for the number of patients exposed to allogeneic RBC transfusion. These trials evaluated a total of 1589 patients. The relative risk (RR) of exposure to allogeneic blood transfusion in those patients randomised to PRP was 0.73 (95%CI 0.59 to 0.90), equating to a relative risk reduction (RRR) of 27% and a risk difference (RD) of 19% (95%CI 10% to 29%). However, significant heterogeneity of treatment effect was observed (p < 0.00001; I² = 79%). When the four trials by Boldt are excluded, the RR is 0.76 (95% CI 0.62 to 0.93). On average, PRP did not significantly reduce the total volume of RBC transfused (weighted mean difference [WMD] -0.69, 95%CI -1.93 to 0.56 units). Trials provided inadequate data regarding the impact of PRP on morbidity, mortality, and hospital length of stay. Trials were generally small and of poor methodological quality. Although the results suggest that PRP is effective in reducing allogeneic RBC transfusion in adult patients undergoing elective surgery, there was considerable heterogeneity of treatment effects and the trials were of poor methodological quality. The available studies provided inadequate data for firm conclusions to be drawn regarding the impact of PRP on clinically important endpoints.

Fibrin sealant use for minimising peri-operative allogeneic blood transfusion

PubMed Central

Carless, Paul A; Henry, David A; Anthony, Danielle M

2014-01-01

Background Fibrin sealants (also referred to as biological glue or fibrin tissue adhesives) have gained increasing popularity as interventions to improve peri-operative (intra- and post-operative) haemostasis and diminish the need for allogeneic red cell transfusion (blood from an unrelated donor). Objectives To examine the efficacy of fibrin sealants in reducing peri-operative blood loss and allogeneic red blood cell (RBC) transfusion. Search methods We identified studies by searching CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (1950 to 2008), EMBASE (1980 to 2008), manufacturer web sites (to March 2008), and bibliographies of relevant published articles. Selection criteria Controlled trials in which adult patients scheduled for elective surgery were randomised to fibrin sealant treatment or to a control group which did not receive fibrin sealant treatment. Trials were eligible if they reported data on the number of patients exposed to allogeneic red cell transfusion, the volume of blood transfused, or blood loss (assessed objectively). Data collection and analysis The primary outcomes measured were the: number of patients exposed to allogeneic red cells, amount of blood transfused, and blood loss. Other outcomes measured were: re-operation due to bleeding, infection, mortality, thrombotic events, and length of hospital stay. Treatment effects were pooled using a random-effects model. Main results Eighteen trials that included a total of 1406 patients reported data on peri-operative exposure to allogeneic RBC transfusion. Fibrin sealant treatment, on average, reduced the rate of exposure to allogeneic RBC transfusion by a relative 37% (relative risk (RR) 0.63, 95% confidence interval (CI) 0.45 to 0.88) and 7% in absolute terms (95% CI 2% to 13%). Fourteen trials, including a total of 853 patients, provided data for post-operative blood loss. In aggregate, fibrin sealant treatment reduced blood loss on average by around 161 ml per patient (95% CI 98.25 to 224.53 ml). In the context of orthopaedic surgery, fibrin sealant treatment reduced post-operative blood loss on average by around 223 ml per patient (95% CI 119.85 to 325.18 ml) and reduced the risk of exposure to allogeneic RBC transfusion by 32% (RR 0.68, 95% CI 0.51 to 0.89). Fibrin sealant treatment was not associated with an increased risk of wound infection (RR 0.61, 95% CI 0.24 to 1.58), any infection (RR 0.93, 95% CI 0.44 to 1.94), haematoma formation (RR 0.46, 95% CI 0.18 to 1.18), or death (RR 0.85, 95% CI 0.38 to 1.89). Hospital length of stay was not reduced in patients treated with fibrin sealant (weighted mean difference (WMD) −0.21 days, 95% CI −0.42 to 0.01 days). Authors’ conclusions Overall, the results suggest that fibrin sealants are efficacious in reducing both post-operative blood loss and peri-operative exposure to allogeneic RBC transfusion. Although treatment-effect heterogeneity was observed for these primary efficacy outcomes, heterogeneity was generally in terms of the size of effect rather than the direction of effect. Fibrin sealants appeared to demonstrate their greatest beneficial effects in the context of orthopaedic surgery, where blood loss is often substantial. Trials not involving orthopaedic surgery generally showed a trend toward decreased post-operative blood loss but the observed reductions were not clinically significant. The majority of trials included in this review were small, which raises concerns about the potential effects of publication bias. Funnel plot assessment indicates that there is some evidence of publication bias in the form of a missing population of small negative trials. We believe that large, methodologically rigorous, randomised controlled trials of fibrin sealants are needed. PMID:12804501

Neuroimaging study of sex differences in the neuropathology of cocaine abuse.

PubMed

Li, Chiang-shan Ray; Kemp, Kathleen; Milivojevic, Verica; Sinha, Rajita

2005-09-01

Female and male substance abusers differ in their disease patterns and clinical outcomes. An important question in addiction neuroscience thus concerns the neural substrates underlying these sex differences. This article aims to examine what is known of the neural mechanisms involved in the sex differences between substance abusers. We reviewed neuroimaging studies that addressed sex differences in cerebral perfusion deficits after chronic cocaine use and in regional brain activation during pharmacologic challenge and cue-induced craving. We also present results from a preliminary study in which cocaine-dependent men and women participated in script-guided imagery of stress- and drug cue-related situations while blood oxygenation level-dependent signals of their brain were acquired in a 1.5T scanner. Spatial pre-processing and statistical analysis of brain images were performed. Regional brain activation was compared between stress and drug cue trials in men versus women. The results of our study showed greater activation in the left uncus and right claustrum (both, statistical threshold of P = 0.01, uncorrected; extent = 10 voxels) in men (n = 5) during drug cue trials compared with stress trials. No brain regions showed greater activation during stress trials compared with drug cue trials. In contrast, women (n = 6) showed greater activation in the right medial and superior frontal gyri during stress trials compared with drug cue trials at the same statistical threshold. No brain regions showed more activation during drug cue trials than during stress trials. The studies reviewed underscore the need to consider sex-related factors in examining the neuropathology of cocaine addiction. Our preliminary results also suggest important sex differences in the effect of stress- and drug cue-associated brain activation in individuals with cocaine use disorder.

The influence of emotional interference on cognitive control: A meta-analysis of neuroimaging studies using the emotional Stroop task.

PubMed

Song, Sensen; Zilverstand, Anna; Song, Hongwen; d'Oleire Uquillas, Federico; Wang, Yongming; Xie, Chao; Cheng, Li; Zou, Zhiling

2017-05-18

The neural correlates underlying the influence of emotional interference on cognitive control remain a topic of discussion. Here, we assessed 16 neuroimaging studies that used an emotional Stroop task and that reported a significant interaction effect between emotion (stimulus type) and cognitive conflict. There were a total of 330 participants, equaling 132 foci for an activation likelihood estimation (ALE) analysis. Results revealed consistent brain activation patterns related to emotionally-salient stimuli (as compared to emotionally-neutral trials) during cognitive conflict trials [incongruent trials (with task-irrelevant information interfering), versus congruent/baseline trials (less disturbance from task-irrelevant information)], that span the lateral prefrontal cortex (dorsolateral prefrontal cortex and inferior frontal gyrus), the medial prefrontal cortex, and the dorsal anterior cingulate cortex. Comparing mild emotional interference trials (without semantic conflict) versus intense emotional interference trials (with semantic conflict), revealed that while concurrent activation in similar brain regions as mentioned above was found for intense emotional interference trials, activation for mild emotional interference trials was only found in the precentral/postcentral gyrus. These data provide evidence for the potential neural mechanisms underlying emotional interference on cognitive control, and further elucidate an important distinction in brain activation patterns for different levels of emotional conflict across emotional Stroop tasks.

GPON FTTH trial: lessons learned

NASA Astrophysics Data System (ADS)

Weis, Erik; Hölzl, Rainer; Breuer, Dirk; Lange, Christoph

2009-11-01

This paper reports on a FTTH field trial with GPON (Gigabit-capable passive optical network) technology in the network of Deutsche Telekom in the region of the cities of Berlin and Potsdam. Focus of this trial was to gain practical experience regarding GPON technology, fibre installation in existing ducts with micro duct technology, fibre cabling in customer buildings and impact on operational processes. Furthermore it is reported on an initial Deutsche Telekom FTTB deployment based on GPON technology in the city of Dresden with the main targets to obtain practical deployment and operation experiences with fibre-based access networks and to provide broadband access to a part of the city formerly not servable by DSL (digital subscriber line) technology.

Sport and physical activity following unicompartmental knee arthroplasty: a systematic review.

PubMed

Waldstein, Wenzel; Kolbitsch, Paul; Koller, Ulrich; Boettner, Friedrich; Windhager, Reinhard

2017-03-01

Unicompartmental knee arthroplasty (UKA) can be a surgical treatment option for patients with high expectations regarding the post-operative level of physical activity. A systematic review was undertaken to answer three research questions: (1) is there an improvement of physical activity based on validated activity scores following UKA? (2) What are the sport disciplines and the sport patterns of UKA patients? (3) What are the pre- and post-operative sport participation rates and the return to activity rates of UKA patients? Following the PRISMA guidelines, EMBASE, MEDLINE, ISI Web of Science and the Cochrane Central Register of Controlled Trials were searched for studies reporting the level of sport and/or physical activity before and after UKA, and/or included at least one activity score before and after UKA. Seventeen studies were identified reporting on 2972 UKAs, of which 89 % were medial UKAs and 92 % were mobile-bearing implants, respectively. Ten studies reported a statistically significant improvement of physical activity following UKA according to the UCLA activity score, the Tegner activity score or the High Activity Arthroplasty Score, respectively. Hiking, cycling and swimming are the most common activities following UKA. Sport participation before the onset of restricting symptoms ranged from 64 to 93 % and slightly decreased by 2-9 % following UKA. The return to activity rate ranged from 87 to 98 %. Patients following UKA are physically active according to validated activity scores. A significant increase in low-impact activities and a decrease in high-impact activities after UKA was observed. Patients with a UKA regularly participate in sports; however, sport participation slightly decreased compared to pre-arthritic levels. This systematic review helps physicians to manage the expectations of patients regarding the level of physical activity following UKA. III.

Student Participation in Rover Field Trials

NASA Astrophysics Data System (ADS)

Bowman, C. D.; Arvidson, R. E.; Nelson, S. V.; Sherman, D. M.; Squyres, S. W.

2001-12-01

The LAPIS program was developed in 1999 as part of the Athena Science Payload education and public outreach, funded by the JPL Mars Program Office. For the past three years, the Athena Science Team has been preparing for 2003 Mars Exploration Rover Mission operations using the JPL prototype Field Integrated Design and Operations (FIDO) rover in extended rover field trials. Students and teachers participating in LAPIS work with them each year to develop a complementary mission plan and implement an actual portion of the annual tests using FIDO and its instruments. LAPIS is designed to mirror an end-to-end mission: Small, geographically distributed groups of students form an integrated mission team, working together with Athena Science Team members and FIDO engineers to plan, implement, and archive a two-day test mission, controlling FIDO remotely over the Internet using the Web Interface for Telescience (WITS) and communicating with each other by email, the web, and teleconferences. The overarching goal of LAPIS is to get students excited about science and related fields. The program provides students with the opportunity to apply knowledge learned in school, such as geometry and geology, to a "real world" situation and to explore careers in science and engineering through continuous one-on-one interactions with teachers, Athena Science Team mentors, and FIDO engineers. A secondary goal is to help students develop improved communication skills and appreciation of teamwork, enhanced problem-solving skills, and increased self-confidence. The LAPIS program will provide a model for outreach associated with future FIDO field trials and the 2003 Mars mission operations. The base of participation will be broadened beyond the original four sites by taking advantage of the wide geographic distribution of Athena team member locations. This will provide greater numbers of students with the opportunity to actively engage in rover testing and to explore the possibilities of science, engineering, and technology.

NextGen Flight Deck Surface Trajectory-Based Operations (STBO): Contingency Holds

NASA Technical Reports Server (NTRS)

Bakowski, Deborah Lee; Hooey, Becky Lee; Foyle, David C.; Wolter, Cynthia A.; Cheng, Lara W. S.

2013-01-01

The purpose of this pilot-in-the-loop taxi simulation was to investigate a NextGen Surface Trajectory-Based Operations (STBO) concept called "contingency holds." The contingency-hold concept parses a taxi route into segments, allowing an air traffic control (ATC) surface traffic management (STM) system to hold an aircraft when necessary for safety. Under nominal conditions, if the intersection or active runway crossing is clear, the hold is removed, allowing the aircraft to continue taxiing without slowing, thus improving taxi efficiency, while minimizing the excessive brake use, fuel burn, and emissions associated with stop-and-go taxi. However, when a potential traffic conflict exists, the hold remains in place as a fail-safe mechanism. In this departure operations simulation, the taxi clearance included a required time of arrival (RTA) to a specified intersection. The flight deck was equipped with speed-guidance avionics to aid the pilot in safely meeting the RTA. On two trials, the contingency hold was not released, and pilots were required to stop. On two trials the contingency hold was released 15 sec prior to the RTA, and on two trials the contingency hold was released 30 sec prior to the RTA. When the hold remained in place, all pilots complied with the hold. Results also showed that when the hold was released at 15-sec or 30-sec prior to the RTA, the 30-sec release allowed pilots to maintain nominal taxi speed, thus supporting continuous traffic flow; whereas, the 15-sec release did not. The contingency-hold concept, with at least a 30-sec release, allows pilots to improve taxiing efficiency by reducing braking, slowing, and stopping, but still maintains safety in that no pilots "busted" the clearance holds. Overall, the evidence suggests that the contingency-hold concept is a viable concept for optimizing efficiency while maintaining safety.

Control of complex motor gestures: orofacial muscle responses to load perturbations of lip during speech.

PubMed

Abbs, J H; Gracco, V L

1984-04-01

The contribution of ascending afferents to the control of speech movement was evaluated by applying unanticipated loads to the lower lip during the generation of combined upper lip-lower lip speech gestures. To eliminate potential contamination due to anticipation or adaptation, loads were applied randomly on only 10-15% of the trials. Physical characteristics of the perturbations were within the normal range of forces and movements involved in natural lip actions for speech. Compensatory responses in multiple facial muscles and lip movements were observed the first time a load was introduced, and achievement of the multimovement speech goals was never disrupted by these perturbations. Muscle responses were seen in the lower lip muscles, implicating corrective, feedback processes. Additionally, compensatory responses to these lower lip loads were also observed in the independently controlled muscles of the upper lip, reflecting the parallel operation of open-loop, sensorimotor mechanisms. Compensatory responses from both the upper and lower lip muscles were observed with small (1 mm) as well as large (15 mm) perturbations. The latencies of these compensatory responses were not discernible by conventional ensemble averaging. Moreover, responses at latencies of lower brain stem-mediated reflexes (i.e., 10-18 ms) were not apparent with inspection of individual records. Response latencies were determined on individual loaded trials through the use of a computer algorithm that took into account the variability of electromyograms (EMG) among the control trials. These latency measures confirmed the absence of brain stem-mediated responses and yielded response latencies that ranged from 22 to 75 ms. Response latencies appeared to be influenced by the time relation between load onset and the initiation of muscle activation. Examination of muscle activity changes for individual loaded trials revealed complementary variations in the magnitude of responses among multiple muscles contributing to a movement compensation. These observations may have implications for limb movement control if multimovement speech gestures are considered analogous to a limb action requiring coordinated movements around multiple joints. In this context, these speech motor control data might be interpreted to suggest that for complex movements, both corrective feedback and open-loop predictive processes are operating, with the latter involved in the control of coordination among multiple movement subcomponents.

Ostomy telehealth for cancer survivors: Design of the Ostomy Self-management Training (OSMT) randomized trial.

PubMed

Sun, Virginia; Ercolano, Elizabeth; McCorkle, Ruth; Grant, Marcia; Wendel, Christopher S; Tallman, Nancy J; Passero, Frank; Raza, Sabreen; Cidav, Zuleyha; Holcomb, Michael; Weinstein, Ronald S; Hornbrook, Mark C; Krouse, Robert S

2018-01-01

An ostomy adversely affects health-related quality of life (HRQOL) in a diverse population of cancer survivors and their caregivers. Hit-or-miss ostomy care, nurse counseling, and community referral have been the primary modes of self-management education and support in the peri-operative setting. Few evidence-based, systematic ostomy self-management programs are available to ensure optimal post-operative care. This paper describes the study design of a telehealth-based Ostomy Self-management Training (OSMT) program for cancer survivors and their caregivers. The study is a three-year, randomized trial that tests the effectiveness of the OSMT program on survivor activation, self-efficacy, and HRQOL. The intervention integrates goal setting and problem-solving approaches to enhance survivor activation and self-efficacy to carry out ostomy care. The curriculum is delivered via four group sessions administered by trained ostomy certified nurses (WOCNs) and peer ostomates. An additional session is offered to caregivers to address their needs in relation to ostomy care. Telehealth approaches through videoconferencing are used to enhance program delivery to participants in three different geographic areas across two time zones. Participants join sessions via real-time videoconferencing from their homes. The OSMT program has high potential to make a positive impact on the unique physical, psychological, social, and spiritual needs of cancer survivors living with a permanent ostomy. The study design, process, and telehealth approach contributes to the success of future dissemination efforts of the intervention into diverse clinical and community settings. Copyright © 2017 Elsevier Inc. All rights reserved.

Gulf War Illness Inflammation Reduction Trial

DTIC Science & Technology

2017-10-01

United States military personnel were deployed to the Kuwaiti Theater of Operations during Operation Desert Shield and Operation Desert Storm (Gulf...differential, plasma proteomics, platelet function studies, and the measurement of multiple coagulation parameters. The pilot study results provide strong

Gulf War Illness Inflammation Reduction Trial

DTIC Science & Technology

2016-10-01

the Kuwaiti Theater of Operations during Operation Desert Shield and Operation Desert Storm (Gulf War). Many veterans of this conflict now suffer...complete blood count with differential, plasma proteomics, platelet function studies, and the measurement of multiple coagulation parameters. The

Priorities for Antiretroviral Therapy Research in Sub-Saharan Africa: A 2002 Consensus Conference in Zambia

PubMed Central

Zulu, Isaac; Schuman, Paula; Musonda, Rosemary; Chomba, Elwyn; Mwinga, Kasonde; Sinkala, Moses; Chisembele, Maureen; Mwaba, Peter; Kasonde, Dorothy; Vermund, Sten H.

2009-01-01

Background A consensus conference was held to discuss priorities for antiretroviral therapy (ART) research in Zambia, one of the world’s most heavily HIV-afflicted nations. Zambia, like other resource-limited settings, has increasing access to highly active antiretroviral therapy (HAART) because of declining drug costs, use of government-purchased generic medications, and increased global donations. For sustained delivery of care with HAART in a resource-constrained medical and public health context, operational research is required and clinical trials are desirable. The priority areas for research are most relevant today given the increasing availability of HAART. Methods A conference was held in Lusaka, Zambia, in January 2002 to discuss priority areas for ART research in Zambia, with participants drawn from a broad cross section of Zambian society. State-of-the-art reviews and 6 intensive small group discussions helped to formulate a suggested research agenda. Results Conference participants believed that the most urgent research priorities were to assess how therapeutic resources could be applied for the greatest overall benefit and to minimize the impact of nonadherence and viral resistance. Identified research priorities were as follows: To determine when to initiate HAART in relation to CD4+ cell count To assess whether HIV/AIDS can be managed well without the use of costly frequent viral load measurements and CD4+ cell count monitoring To assess whether HIV/AIDS can be managed in the same fashion in patients coinfected with opportunistic infections such as tuberculosis and HIV-related chronic diarrhea, taking into consideration complications that may occur in tuberculosis such as immune reconstitution syndrome and medication malabsorption in the presence of diarrhea To carefully assess and characterize toxicities, adverse effects, and viral resistance patterns in Zambia, including studies of mothers exposed to prepartum single-dose nevirapine To conduct operational research to assess clinical and field-based strategies to maximize adherence for better outcomes of ART in Zambia To assess ART approaches most valuable for pediatric and adolescent patients in Zambia Conference participants recommended that HIV-related clinical care and research be integrated within home-based care services and operated within the existing health delivery structures to ensure sustainability, reduce costs, and strengthen the structures. Conclusion Our consensus was that antiretroviral clinical trials and operational research are essential for Zambia to address the new challenges arising from increasing ART availability. There is global consensus that antiretroviral clinical trials in resource-constrained countries are possible, and the capacity for such trials should be developed further in Africa. PMID:15213567

Randomised controlled trial of labouring in water compared with standard of augmentation for management of dystocia in first stage of labour

PubMed Central

Cluett, Elizabeth R; Pickering, Ruth M; Getliffe, Kathryn; Saunders, Nigel James St George

2004-01-01

Objectives To evaluate the impact of labouring in water during first stage of labour on rates of epidural analgesia and operative delivery in nulliparous women with dystocia. Design Randomised controlled trial. Setting University teaching hospital in southern England. Participants 99 nulliparous women with dystocia (cervical dilation rate < 1 cm/hour in active labour) at low risk of complications. Interventions Immersion in water in birth pool or standard augmentation for dystocia (amniotomy and intravenous oxytocin). Main outcome measures Primary: epidural analgesia and operative delivery rates. Secondary: augmentation rates with amniotomy and oxytocin, length of labour, maternal and neonatal morbidity including infections, maternal pain score, and maternal satisfaction with care. Results Women randomised to immersion in water had a lower rate of epidural analgesia than women allocated to augmentation (47% v 66%, relative risk 0.71 (95% confidence interval 0.49 to 1.01), number needed to treat for benefit (NNT) 5). They showed no difference in rates of operative delivery (49% v 50%, 0.98 (0.65 to 1.47), NNT 98), but significantly fewer received augmentation (71% v 96%, 0.74 (0.59 to 0.88), NNT 4) or any form of obstetric intervention (amniotomy, oxytocin, epidural, or operative delivery) (80% v 98%, 0.81 (0.67 to 0.92), NNT 5). More neonates of women in the water group were admitted to the neonatal unit (6 v 0, P = 0.013), but there was no difference in Apgar score, infection rates, or umbilical cord pH. Conclusions Labouring in water under midwifery care may be an option for slow progress in labour, reducing the need for obstetric intervention, and offering an alternative pain management strategy. PMID:14744822

One-year follow-up of tension-free vaginal tape (TVT) and trans-obturator suburethral tape from inside to outside (TVT-O) for surgical treatment of female stress urinary incontinence: a prospective randomised trial.

PubMed

Zullo, Marzio Angelo; Plotti, Francesco; Calcagno, Marco; Marullo, Elettra; Palaia, Innocenza; Bellati, Filippo; Basile, Stefano; Muzii, Ludovico; Angioli, Roberto; Panici, Pierluigi Benedetti

2007-05-01

To compare tension-free vaginal tape (TVT) and trans-obturator suburethral tape from inside to outside (TVT-O) for surgical treatment of stress urinary incontinence (SUI) for complications (primary end point) and success rate (secondary end point). Seventy-two consecutive patients, with a mean age of 53.2 yr (range: 38-69 yr) and affected by SUI, were included in this randomised controlled trial. After preoperative assessment, patients were randomly allocated to the TVT or TVT-O procedure. Operative time, perioperative complications, and hospital stay were prospectively recorded. Cure of SUI was defined as no leakage of urine during the stress test at urodynamic testing at the 12-mo evaluation. The Wilcoxon signed rank sum test, Mann-Whitney U test, McNemar test, and Fisher exact test were used to verify statistical significance, set at p<0.05. All patients were evaluable at the 12-mo follow-up. The characteristics of patients were well balanced between groups after randomisation. The mean operative time was significantly shorter in the TVT-O group. Perioperative complications were significantly more common after the retropubic approach (5% and 27% in TVT-O and TVT groups, respectively, p<0.04). The groups did not differ significantly in intraoperative blood loss, hospital stays, and time to return to normal activities. Sixty-five patients (90%) were successfully treated for SUI 12 mo after the operation (89% and 91% for TVT-O and TVT groups, respectively). Both techniques appear to be equally effective in the surgical treatment of SUI. However, TVT-O had a shorter operative time and lower overall perioperative complication rate.

Comparison of ultrasonic shears and traditional suture ligature for vaginal hysterectomy: randomized controlled trial.

PubMed

Fitz-Gerald, Alison Louise; Tan, Jason; Chan, Kok-Weng; Polyakov, Alex; Edwards, Geoff N; Najjar, Haider; Tsaltas, Jim; Vollenhoven, Beverley

2013-01-01

To compare operating time, intraoperative blood loss, postoperative analgesia, and length of hospital stay using ultrasonic shears vs traditional suture ligature in vaginal hysterectomy. Randomized controlled trial (Canadian Task Force classification I). Gynecology units within a single health network, university hospital. Forty women requiring vaginal hysterectomy because of benign disease. Vaginal hysterectomy performed using either ultrasonically activated shears (USS) or traditional suture ligatures. Twenty-one patients were randomized to the USS arm, and 19 patients to the traditional suture ligature arm. Patient characteristics were comparable. Mean (SD) hysterectomy time and was similar in both the USS and traditional arms, 28.66 (4.0) minutes vs 32.37 (3.18) minutes (p = .47), as was total operating time, 97.38 (8.9) minutes vs 91.63 (7.69) minutes (p = .63). Operative blood loss was significantly decreased in the USS group: 62.63 (12.46) mL vs 136.05 (21.54) mL (p = .006). There was, however, no significant change in hemoglobin concentration between the 2 groups: 19.53 (1.79) g/L vs -16.72 (2.5) g/L. There was no significant difference in mean oxycodone use: 9.29 (2.66) mg vs 8.06 (3.19) mg (p = .77). Length of hospital stay was similar in both groups: 58.98 (3.27) hours vs 60.05 (6.48) hours (p = .88). There was no significant difference in overall complication rates between the groups. Although the Harmonic scalpel system, compared with the traditional suture ligation method, seems to be a safe alternative for securing the pedicles in vaginal hysterectomy, it offers no benefit insofar as operative time, reduction in clinically significant blood loss, and analgesic requirements. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

What we have learned about intrapartum fetal monitoring trials in the MFMU Network.

PubMed

Bloom, Steven L; Belfort, Michael; Saade, George

2016-08-01

The vast majority of pregnant women are subjected to electronic fetal heart monitoring during labor. There is limited evidence to support its benefit compared with intermittent auscultation. In addition, there is significant variability in interpretation and its false-positive rate is high. The latter may have contributed to the rise in operative deliveries. In order to address the critical need for better approaches to intrapartum monitoring, the MFMU Network has completed two large multisite randomized trials, one to evaluate fetal pulse oximetry and the other to evaluate fetal ECG ST segment analysis (STAN). Both of these technologies had been approved for clinical use in the United States based on prior smaller trials. These technologies were evaluated in laboring women near term and their primary outcomes were overall cesarean delivery for the oximetry trial and a composite adverse neonatal outcome for STAN. Both the trials failed to show a benefit of the technology, neither in the rates of operative deliveries nor in the rates of adverse neonatal outcomes. The experience with these trials, summarized in this report, highlights the need for rigorous evidence before introduction of new technology into clinical practice and provides a blueprint for future trials to address the need for better intrapartum monitoring approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of design strategies for a three-arm clinical trial with time-to-event endpoint: Power, time-to-analysis, and operational aspects.

PubMed

Asikanius, Elina; Rufibach, Kaspar; Bahlo, Jasmin; Bieska, Gabriele; Burger, Hans Ulrich

2016-11-01

To optimize resources, randomized clinical trials with multiple arms can be an attractive option to simultaneously test various treatment regimens in pharmaceutical drug development. The motivation for this work was the successful conduct and positive final outcome of a three-arm randomized clinical trial primarily assessing whether obinutuzumab plus chlorambucil in patients with chronic lympocytic lymphoma and coexisting conditions is superior to chlorambucil alone based on a time-to-event endpoint. The inference strategy of this trial was based on a closed testing procedure. We compare this strategy to three potential alternatives to run a three-arm clinical trial with a time-to-event endpoint. The primary goal is to quantify the differences between these strategies in terms of the time it takes until the first analysis and thus potential approval of a new drug, number of required events, and power. Operational aspects of implementing the various strategies are discussed. In conclusion, using a closed testing procedure results in the shortest time to the first analysis with a minimal loss in power. Therefore, closed testing procedures should be part of the statistician's standard clinical trials toolbox when planning multiarm clinical trials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Best Practices for the Application of Functional Near Infrared Spectroscopy to Operator State Sensing

NASA Technical Reports Server (NTRS)

Harrivel, Angela R.; Hylton, Alan G.; Hearn, Tristan A.

2012-01-01

Functional Near Infrared Spectroscopy (fNIRS) is an emerging neuronal measurement technique with many advantages for application in operational and training contexts. Instrumentation and protocol improvements, however, are required to obtain useful signals and produce expeditiously self-applicable, comfortable and unobtrusive headgear. Approaches for improving the validity and reliability of fNIRS data for the purpose of sensing the mental state of commercial aircraft operators are identified, and an exemplary system design for attentional state monitoring is outlined. Intelligent flight decks of the future can be responsive to state changes to optimally support human performance. Thus, the identification of cognitive performance decrement, such as lapses in operator attention, may be used to predict and avoid error-prone states. We propose that attentional performance may be monitored with fNIRS through the quantification of hemodynamic activations in cortical regions which are part of functionally-connected attention and resting state networks. Activations in these regions have been shown to correlate with behavioral performance and task engagement. These regions lie beneath superficial tissue in head regions beyond the forehead. Headgear development is key to reliably and robustly accessing locations beyond the hair line to measure functionally-connected networks across the whole head. Human subject trials using both fNIRS and functional Magnetic Resonance Imaging (fMRI) will be used to test this system. Data processing employs Support Vector Machines for state classification based on the fNIRS signals. If accurate state classification is achieved based on sensed activation patterns, fNIRS will be shown to be useful for monitoring attentional performance.

DeLLITE depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial.

PubMed

Kerse, Ngaire; Falloon, Karen; Moyes, Simon A; Hayman, Karen J; Dowell, Tony; Kolt, Gregory S; Elley, C Raina; Hatcher, Simon; Peri, Kathy; Keeling, Sally; Robinson, Elizabeth; Parsons, John; Wiles, Janine; Arroll, Bruce

2008-05-24

Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects. The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report). Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs. Australian and New Zealand Clinical Trials Register ACTRN12605000475640.

Deep Cerebellar Nuclei Play an Important Role in Two-Tone Discrimination on Delay Eyeblink Conditioning in C57BL/6 Mice

PubMed Central

Sakamoto, Toshiro; Endo, Shogo

2013-01-01

Previous studies have shown that deep cerebellar nuclei (DCN)-lesioned mice develop conditioned responses (CR) on delay eyeblink conditioning when a salient tone conditioned stimulus (CS) is used, which suggests that the cerebellum potentially plays a role in more complicated cognitive functions. In the present study, we examined the role of DCN in tone frequency discrimination in the delay eyeblink-conditioning paradigm. In the first experiment, DCN-lesioned and sham-operated mice were subjected to standard simple eyeblink conditioning under low-frequency tone CS (LCS: 1 kHz, 80 dB) or high-frequency tone CS (HCS: 10 kHz, 70 dB) conditions. DCN-lesioned mice developed CR in both CS conditions as well as sham-operated mice. In the second experiment, DCN-lesioned and sham-operated mice were subjected to two-tone discrimination tasks, with LCS+ (or HCS+) paired with unconditioned stimulus (US), and HCS− (or LCS−) without US. CR% in sham-operated mice increased in LCS+ (or HCS+) trials, regardless of tone frequency of CS, but not in HCS− (or LCS−) trials. The results indicate that sham-operated mice can discriminate between LCS+ and HCS− (or HCS+ and LCS−). In contrast, DCN-lesioned mice showed high CR% in not only LCS+ (or HCS+) trials but also HCS− (or LCS−) trials. The results indicate that DCN lesions impair the discrimination between tone frequency in eyeblink conditioning. Our results suggest that the cerebellum plays a pivotal role in the discrimination of tone frequency. PMID:23555821

Preoperative clonidine use in trans-sphenoidal pituitary adenoma surgeries - a randomized controlled trial.

PubMed

Bajaj, Jitin; Mittal, Radhe Shyam; Sharma, Achal

2017-02-01

Pituitary masses are common lesions accounting for about 15-20% of all brain tumours. Oozing blood is an annoyance in microscopic sublabial trans-sphenoidal approach for these masses. There have been many ways of reducing the ooze, having their own pros and cons. To find out the efficacy and safety of clonidine in reducing blood loss in pituitary adenoma surgery through a randomized masked trial. It was a prospective randomized controlled trial done. Total 50 patients of pituitary adenomas were randomized into two groups. Group A (25 patients) was given 200 μg clonidine orally, while Group B (25 patients) was given placebo. Surgeon, anaesthesiologist and patient were blinded for the trial. Sublabial trans-septal trans-sphenoidal approach to sella and excision of mass was performed in each patient. Patients were studied for pre-, intra- and post-operative blood pressure and heart rate, pre- and post-operative imaging findings, intra-operative blood loss, bleeding grading by surgeon, surgeon's satisfaction about condition of specific part and quality of surgical field, operative time and extent of resection. Blood loss during the surgery, operative time and bleeding grading by the surgeon were found significantly less in the clonidine group, while quality of surgical field, condition of the specific part and extent of resection were found significantly better in the clonidine group (p value <.05). There was no untoward adverse effect of the drug in the test group. Clonidine is a safe and effective drug to reduce bleeding in trans-sphenoidal microscopic pituitary adenoma surgeries.

Self-Reported Knee Instability Before and After Total Knee Replacement Surgery.

PubMed

Fleeton, Genevieve; Harmer, Alison R; Nairn, Lillias; Crosbie, Jack; March, Lyn; Crawford, Ross; van der Esch, Martin; Fransen, Marlene

2016-04-01

To determine the prevalence and burden of pain and activity limitations associated with retaining presurgery self-reported knee instability 6 months after total knee replacement (TKR) surgery and to identify early potentially modifiable risk factors for retaining knee instability in the operated knee after TKR surgery. A secondary analysis was performed using measures obtained from 390 participants undergoing primary unilateral TKR and participating in a randomized clinical trial. Self-reported knee instability was measured using 2 items from the Activities of Daily Living Scale of the Knee Outcome Survey. Outcome measures were knee pain (range 0-20) and physical function (range 0-68) on the Western Ontario and McMaster Universities Arthritis Index (WOMAC), stair-climb power, 50-foot walk time, knee range of motion, and isometric knee flexion and extension strength. In this study, 72% of participants reported knee instability just prior to surgery, with 32% retaining instability in the operated knee 6 months after surgery. Participants retaining operated knee instability had significantly more knee pain and activity limitations 6 months after surgery, with mean ± SD WOMAC scores of 4.8 ± 3.7 and 17.5 ± 11.1, respectively, compared to participants without knee instability, with 2.9 ± 3.1 and 9.8 ± 9.2. The multivariable predictor model for retained knee instability included a high comorbidity score (>6), low stair-climb power (<150 watts), more pain in the operated knee (>7 of 20), and younger age (<60 years). Self-reported knee instability is highly prevalent before and after TKR surgery and is associated with a considerable burden of pain and activity limitation in the operated knee. Increasing lower extremity muscle power may reduce the risk of retaining knee instability after TKR surgery. © 2016, American College of Rheumatology.

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.

Epidemiology of clinical trials of medicines in respiratory diseases in Europe and Italy.

PubMed

Bodini, Roberta; Santus, Pierachille; Di Marco, Fabiano; Aliberti, Stefano; Centanni, Stefano; Blasi, Francesco; Rizzi, Andrea; Recchia, Giuseppe

2017-04-01

Clinical trials play a key role in advancing medical knowledge, improving patient care and promoting economic growth in Europe. We have assessed the clinical trial activity in any respiratory diseases in Europe, with a specific focus on Italy. Information from public sources (EFPIA, clinicaltrials.gov, clinicaltrialsregister. eu, AIFA) was used to describe clinical trial activity of in respiratory diseases in Europe and by country. In 2015, 3908 clinical trials were reported in Europe, 386 in respiratory diseases (9.9%). Germany was the first country both as absolute number (76 trials) and as percentage within country trials (14%), followed by Poland. Spain, Italy and France were the countries with the lowest number and percentage of trials in respiratory diseases. In 2013, the Italian Drug Agency reported 9 trials with respiratory compounds in Italy (2.1% of overall trials, 12ˆ position in the therapeutic area rank), 33% in phase 2 and 66% in phase 3. No phase 1 or phase 4 trials were reported for respiratory trials. Prevalence of respiratory trials by non-profit sponsors (28.3%) was below the average for the country (38.3%). Europe has a greater potential for clinical research on drugs for respiratory diseases, particularly in countries with less activity, such as Spain, France and Italy, that should identify and implement actions to increase attractiveness for clinical trials of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Basic considerations during outsourcing of clinical data management services].

PubMed

Shen, Tong; Liu, Yan

2015-11-01

With worldwide improvements in the regulations of international and domestic clinical trial conductions, the quality of clinical trials and trial data management are receiving a great deal of attention. To ensure the quality of clinical trials, maintain business flexibilities and effectively utilize internal and external resources, the outsourcing model is used in the management of clinical data in operation of pharmaceutical companies. The essential criteria of a successful outsourcing mode in clinical trial are selection of qualified contract research organizations (CRO); establishment of appropriate outsourcing model, and generation of effective quality control systems to ensure the authenticity, integrity and accuracy of the clinical trial data.

Strengthening capacity for AIDS vaccine research: analysis of the Pfizer Global Health Fellows Program and the International AIDS Vaccine Initiative

PubMed Central

2013-01-01

Background Industry partnerships can help leverage resources to advance HIV/AIDS vaccine research, service delivery, and policy advocacy goals. This often involves capacity building for international and local non-governmental organizations (NGOs). International volunteering is increasingly being used as a capacity building strategy, yet little is known about how corporate volunteers help to improve performance of NGOs in the fight against HIV/AIDS. Methods This case study helps to extend our understanding by analyzing how the Pfizer Global Health Fellows (GHF) program helped develop capacity of the International AIDS Vaccine Initiative (IAVI), looking specifically at Fellowship activities in South Africa, Kenya, and Uganda. From 2005–2009, 8 Pfizer GHF worked with IAVI and local research centers to strengthen capacity to conduct and monitor vaccine trials to meet international standards and expand trial activities. Data collection for the case study included review of Fellow job descriptions, online journals, evaluation reports, and interviews with Fellows and IAVI staff. Qualitative methods were used to analyze factors which influenced the process and outcomes of capacity strengthening. Results Fellows filled critical short-term expert staffing needs at IAVI as well as providing technical assistance and staff development activities. Capacity building included assistance in establishing operating procedures for the start-up period of research centers; training staff in Good Clinical Practice (GCP); developing monitoring capacity (staff and systems) to assure that centers are audit-ready at all times; and strategic planning for data management systems. Factors key to the success of volunteering partnerships included similarities in mission between the corporate and NGO partners, expertise and experience of Fellows, and attitudes of partner organization staff. Conclusion By developing standard operating procedures, ensuring that monitoring and regulatory compliance systems were in place, training African investigators and community members, and engaging in other systems strengthening activities, the GHF program helped IAVI to accelerate vaccine development activities in the field, and to develop the organization’s capacity to manage change in the future. Our study suggests that a program of sustained corporate volunteering over several years may increase organizational learning and trust, leading to stronger capacity to advance and achieve NGO goals. PMID:24088300

Strengthening capacity for AIDS vaccine research: analysis of the Pfizer Global Health Fellows program and the International AIDS Vaccine Initiative.

PubMed

Vian, Taryn; Koseki, Sayaka; Feeley, Frank G; Beard, Jennifer

2013-10-02

Industry partnerships can help leverage resources to advance HIV/AIDS vaccine research, service delivery, and policy advocacy goals. This often involves capacity building for international and local non-governmental organizations (NGOs). International volunteering is increasingly being used as a capacity building strategy, yet little is known about how corporate volunteers help to improve performance of NGOs in the fight against HIV/AIDS. This case study helps to extend our understanding by analyzing how the Pfizer Global Health Fellows (GHF) program helped develop capacity of the International AIDS Vaccine Initiative (IAVI), looking specifically at Fellowship activities in South Africa, Kenya, and Uganda. From 2005-2009, 8 Pfizer GHF worked with IAVI and local research centers to strengthen capacity to conduct and monitor vaccine trials to meet international standards and expand trial activities. Data collection for the case study included review of Fellow job descriptions, online journals, evaluation reports, and interviews with Fellows and IAVI staff. Qualitative methods were used to analyze factors which influenced the process and outcomes of capacity strengthening. Fellows filled critical short-term expert staffing needs at IAVI as well as providing technical assistance and staff development activities. Capacity building included assistance in establishing operating procedures for the start-up period of research centers; training staff in Good Clinical Practice (GCP); developing monitoring capacity (staff and systems) to assure that centers are audit-ready at all times; and strategic planning for data management systems. Factors key to the success of volunteering partnerships included similarities in mission between the corporate and NGO partners, expertise and experience of Fellows, and attitudes of partner organization staff. By developing standard operating procedures, ensuring that monitoring and regulatory compliance systems were in place, training African investigators and community members, and engaging in other systems strengthening activities, the GHF program helped IAVI to accelerate vaccine development activities in the field, and to develop the organization's capacity to manage change in the future. Our study suggests that a program of sustained corporate volunteering over several years may increase organizational learning and trust, leading to stronger capacity to advance and achieve NGO goals.

Do workplace physical activity interventions improve mental health outcomes?

PubMed

Chu, A H Y; Koh, D; Moy, F M; Müller-Riemenschneider, F

2014-06-01

Mental health is an important issue in the working population. Interventions to improve mental health have included physical activity. To review evidence for the effectiveness of workplace physical activity interventions on mental health outcomes. A literature search was conducted for studies published between 1990 and August 2013. Inclusion criteria were physical activity trials, working populations and mental health outcomes. Study quality was assessed using the Jadad scale. Of 3684 unique articles identified, 17 met all selection criteria, including 13 randomized controlled trials, 2 comparison trials and 2 controlled trials. Studies were grouped into two key intervention areas: physical activity and yoga exercise. Of eight high-quality trials, two provided strong evidence for a reduction in anxiety, one reported moderate evidence for an improvement in depression symptoms and one provided limited evidence on relieving stress. The remaining trials did not provide evidence on improved mental well-being. Workplace physical activity and yoga programmes are associated with a significant reduction in depressive symptoms and anxiety, respectively. Their impact on stress relief is less conclusive. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Transverse occiput position: Using manual Rotation to aid Normal birth and improve delivery OUTcomes (TURN-OUT): A study protocol for a randomised controlled trial.

PubMed

de Vries, Bradley; Phipps, Hala; Kuah, Sabrina; Pardey, John; Ludlow, Joanne; Bisits, Andrew; Park, Felicity; Kowalski, David; Hyett, Jon A

2015-08-18

Fetal occiput transverse position in the form of deep transverse arrest has long been associated with caesarean section and instrumental vaginal delivery. Occiput transverse position incidentally found in the second stage of labour is also associated with operative delivery in high risk cohorts. There is evidence from cohort studies that prophylactic manual rotation reduces the caesarean section rate. This is a protocol for a double blind, multicentre, randomised, controlled clinical trial to define whether this intervention decreases the operative delivery (caesarean section, forceps or vacuum delivery) rate. Eligible participants will be ≥37 weeks pregnant, with a singleton pregnancy, and a cephalic presentation in the occiput transverse position on transabdominal ultrasound early in the second stage of labour. Based on a background risk of operative delivery of 49%, for a reduction to 35%, an alpha value of 0.05 and a beta value of 0.2, 416 participants will need to be enrolled. Participants will be randomised to either prophylactic manual rotation or a sham procedure. The primary outcome will be operative delivery. Secondary outcomes will be caesarean section, significant maternal mortality and morbidity, and significant perinatal mortality and morbidity. Analysis will be on an intention-to-treat basis. Primary and secondary outcomes will be compared using a chi-squared test. A logistic regression for the primary outcome will be undertaken to account for potential confounders. This study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, Sydney, Australia, (protocol number: X110410). This trial addresses an important clinical question concerning a commonly used procedure which has the potential to reduce operative delivery and its associated complications. Some issues discussed in the protocol include methods of assessing risk of bias due to inadequate masking of a procedural interventions, variations in intervention efficacy due to operator experience and the recruitment difficulties associated with intrapartum studies. This trial was registered with the Australian New Zealand Clinical Trials Registry (identifier: ACTRN12613000005752 ) on 4 January 2013.

Influences on recruitment to randomised controlled trials in mental health settings in England: a national cross-sectional survey of researchers working for the Mental Health Research Network

PubMed Central

2014-01-01

Background Recruitment to trials is complex and often protracted; selection bias may compromise generalisability. In the mental health field (as elsewhere), diverse factors have been described as hindering researcher access to potential participants and various strategies have been proposed to overcome barriers. However, the extent to which various influences identified in the literature are operational across mental health settings in England has not been systematically examined. Methods A cross-sectional, online survey of clinical studies officers employed by the Mental Health Research Network in England to recruit to trials from National Health Service mental health services. The bespoke questionnaire invited participants to report exposure to specified influences on recruitment, the perceived impact of these on access to potential participants, and to describe additional positive or negative influences on recruitment. Analysis employed descriptive statistics, the framework approach and triangulation of data. Results Questionnaires were returned by 98 (58%) of 170 clinical studies officers who reported diverse experience. Data demonstrated a disjunction between policy and practice. While the particulars of trial design and various marketing and communication strategies could influence recruitment, consensus was that the culture of NHS mental health services is not conducive to research. Since financial rewards for recruitment paid to Trusts and feedback about studies seldom reaching frontline services, clinicians were described as distanced from research. Facing continual service change and demanding clinical workloads, clinicians generally did not prioritise recruitment activities. Incentives to trial participants had variable impact on access but recruitment could be enhanced by engagement of senior investigators and integrating referral with routine practice. Comprehensive, robust feasibility studies and reciprocity between researchers and clinicians were considered crucial to successful recruitment. Conclusions In the mental health context, researcher access to potential trial participants is multiply influenced. Gatekeeping clinicians are faced with competing priorities and resources constrain research activity. It seems that environmental adjustment predicated on equitable resource allocation is needed if clinicians in NHS mental health services are to fully support the conduct of randomised controlled trials. Whilst cultural transformation, requiring changes in assumptions and values, is complex, our findings suggest that attention to practical matters can support this and highlight issues requiring careful consideration. PMID:24533721

Influences on recruitment to randomised controlled trials in mental health settings in England: a national cross-sectional survey of researchers working for the Mental Health Research Network.

PubMed

Borschmann, Rohan; Patterson, Sue; Poovendran, Dilkushi; Wilson, Danielle; Weaver, Tim

2014-02-17

Recruitment to trials is complex and often protracted; selection bias may compromise generalisability. In the mental health field (as elsewhere), diverse factors have been described as hindering researcher access to potential participants and various strategies have been proposed to overcome barriers. However, the extent to which various influences identified in the literature are operational across mental health settings in England has not been systematically examined. A cross-sectional, online survey of clinical studies officers employed by the Mental Health Research Network in England to recruit to trials from National Health Service mental health services. The bespoke questionnaire invited participants to report exposure to specified influences on recruitment, the perceived impact of these on access to potential participants, and to describe additional positive or negative influences on recruitment. Analysis employed descriptive statistics, the framework approach and triangulation of data. Questionnaires were returned by 98 (58%) of 170 clinical studies officers who reported diverse experience. Data demonstrated a disjunction between policy and practice. While the particulars of trial design and various marketing and communication strategies could influence recruitment, consensus was that the culture of NHS mental health services is not conducive to research. Since financial rewards for recruitment paid to Trusts and feedback about studies seldom reaching frontline services, clinicians were described as distanced from research. Facing continual service change and demanding clinical workloads, clinicians generally did not prioritise recruitment activities. Incentives to trial participants had variable impact on access but recruitment could be enhanced by engagement of senior investigators and integrating referral with routine practice. Comprehensive, robust feasibility studies and reciprocity between researchers and clinicians were considered crucial to successful recruitment. In the mental health context, researcher access to potential trial participants is multiply influenced. Gatekeeping clinicians are faced with competing priorities and resources constrain research activity. It seems that environmental adjustment predicated on equitable resource allocation is needed if clinicians in NHS mental health services are to fully support the conduct of randomised controlled trials. Whilst cultural transformation, requiring changes in assumptions and values, is complex, our findings suggest that attention to practical matters can support this and highlight issues requiring careful consideration.

Effects of a pre-operative home-based inspiratory muscle training programme on perceived health-related quality of life in patients undergoing coronary artery bypass graft surgery.

PubMed

Valkenet, K; Trappenburg, J C A; Hulzebos, E H; van Meeteren, N L U; Backx, F J G

2017-09-01

Pre-operative inspiratory muscle training has been shown to decrease the incidence of postoperative pneumonia and length of hospital stay in patients undergoing coronary artery bypass graft surgery (CABG). This study investigated if this decrease acted as a mediator on the time course of quality of life. Complementary analyses of a published randomised controlled trial. The initial trial included patients awaiting CABG surgery at a Dutch university hospital. The secondary analyses used data from the initial trial for patients who had completed at least one quality-of-life questionnaire. Participants were allocated at random to the intervention group or the usual care group. The intervention group followed a home-based pre-operative inspiratory muscle training programme. Quality of life was measured at five time points. Between-group differences in quality-of-life scores were analysed using mixed linear modelling. The secondary analyses used data for 235 patients. In line with the initial trial, pneumonia and length of hospital stay were decreased significantly in the intervention group. The time courses for all patients showed significant improvements in quality of life after surgery compared with baseline. No significant differences in quality of life were observed over time between the two groups. Despite decreased incidence of pneumonia and length of hospital stay in the intervention group, this study did not find any improvements in quality of life due to the pre-operative home-based inspiratory muscle training programme. Clinical trial registration number ISRCTN17691887. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Randomized trial for superiority of high field strength intra-operative magnetic resonance imaging guided resection in pituitary surgery.

PubMed

Tandon, Vivek; Raheja, Amol; Suri, Ashish; Chandra, P Sarat; Kale, Shashank S; Kumar, Rajinder; Garg, Ajay; Kalaivani, Mani; Pandey, Ravindra M; Sharma, Bhawani S

2017-03-01

Till date there are no randomized trials to suggest the superiority of intra-operative magnetic resonance imaging (IOMRI) guided trans-sphenoidal pituitary resection over two dimensional fluoroscopic (2D-F) guided resections. We conducted this trial to establish the superiority of IOMRI in pituitary surgery. Primary objective was to compare extent of tumor resection between the two study arms. It was a prospective, randomized, outcome assessor and statistician blinded, two arm (A: IOMRI, n=25 and B: 2D-F, n=25), parallel group clinical trial. 4 patients from IOMRI group cross-over to 2D-F group and were consequently analyzed in latter group, based on modified intent to treat method. A total of 50 patients were enrolled till completion of trial (n=25 in each study arm). Demographic profile and baseline parameters were comparable among the two arms (p>0.05) except for higher number of endoscopic procedures and experienced neurosurgeons (>10years) in arm B (p=0.02, 0.002 respectively). Extent of resection was similar in both study arms (A, 94.9% vs B, 93.6%; p=0.78), despite adjusting for experience of operating surgeon and use of microscope/endoscope for surgical resection. We observed that use of IOMRI helped optimize the extent of resection in 5/20 patients (25%) for pituitary tumor resection in-group A. Present study failed to observe superiorty of IOMRI over conventional 2D-F guided resection in pituitary macroadenoma surgery. By use of this technology, younger surgeons could validate their results intra-operatively and hence could increase EOR without causing any increase in complications. Copyright © 2016 Elsevier Ltd. All rights reserved.

UK DRAFFT - A randomised controlled trial of percutaneous fixation with kirschner wires versus volar locking-plate fixation in the treatment of adult patients with a dorsally displaced fracture of the distal radius

PubMed Central

2011-01-01

Background Fractures of the distal radius are extremely common injuries in adults. However, the optimal management remains controversial. In general, fractures of the distal radius are treated non-operatively if the bone fragments can be held in anatomical alignment by a plaster cast or orthotic. However, if this is not possible, then operative fixation is required. There are several operative options but the two most common in the UK, are Kirschner-wire fixation (K-wires) and volar plate fixation using fixed-angle screws (locking-plates). The primary aim of this trial is to determine if there is a difference in the Patient-Reported Wrist Evaluation one year following K-wire fixation versus locking-plate fixation for adult patients with a dorsally-displaced fracture of the distal radius. Methods/design All adult patients with an acute, dorsally-displaced fracture of the distal radius, requiring operative fixation are potentially eligible to take part in this study. A total of 390 consenting patients will be randomly allocated to either K-wire fixation or locking-plate fixation. The surgery will be performed in trauma units across the UK using the preferred technique of the treating surgeon. Data regarding wrist function, quality of life, complications and costs will be collected at six weeks and three, six and twelve months following the injury. The primary outcome measure will be wrist function with a parallel economic analysis. Discussion This pragmatic, multi-centre trial is due to deliver results in December 2013. Trial registration Current Controlled Trials ISRCTN31379280 UKCRN portfolio ID 8956 PMID:21914196

The CORONIS Trial. International study of caesarean section surgical techniques: a randomised fractional, factorial trial

PubMed Central

2007-01-01

Background Caesarean section is one of the most commonly performed operations on women throughout the world. Rates have increased in recent years – about 20–25% in many developed countries. Rates in other parts of the world vary widely. A variety of surgical techniques for all elements of the caesarean section operation are in use. Many have not yet been rigorously evaluated in randomised controlled trials, and it is not known whether any are associated with better outcomes for women and babies. Because huge numbers of women undergo caesarean section, even small differences in post-operative morbidity rates between techniques could translate into improved health for substantial numbers of women, and significant cost savings. Design CORONIS is a multicentre, fractional, factorial randomised controlled trial and will be conducted in centres in Argentina, Ghana, India, Kenya, Pakistan and Sudan. Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision. Five comparisons will be carried out in one trial, using a 2 × 2 × 2 × 2 × 2 fractional factorial design. This design has rarely been used, but is appropriate for the evaluation of several procedures which will be used together in clinical practice. The interventions are: • Blunt versus sharp abdominal entry • Exteriorisation of the uterus for repair versus intra-abdominal repair • Single versus double layer closure of the uterus • Closure versus non-closure of the peritoneum (pelvic and parietal) • Chromic catgut versus Polyglactin-910 for uterine repair The primary outcome is death or maternal infectious morbidity (one or more of the following: antibiotic use for maternal febrile morbidity during postnatal hospital stay, antibiotic use for endometritis, wound infection or peritonitis) or further operative procedures; or blood transfusion. The sample size required is 15,000 women in total; at least 7,586 women in each comparison. Discussion Improvements in health from optimising caesarean section techniques are likely to be more significant in developing countries, because the rates of postoperative morbidity in these countries tend to be higher. More women could therefore benefit from improvements in techniques. Trial registration The CORONIS Trial is registered in the Current Controlled Trials registry. ISCRTN31089967. PMID:18336721

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, T; Choobun, T; Peeyananjarassri, K; Islam, M

2004-01-01

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics are prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum and/or forceps deliveries. We searched the Cochrane Pregnancy and Childbirth Group trials register (November 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003) and MEDLINE (1966 to November 2003). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Four reviewers assessed trial eligibility and methodological quality. Two reviewers extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all reviewers. We assessed methodological quality of the included trial using the standard Cochrane criteria and the CONSORT statement of randomised controlled trials. We calculated the relative risks using a fixed effect model and all the reviewers interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine outcomes specified in this review. It reported seven women with endomyometritis in the group given no antibiotic and none in prophylactic antibiotic group. This difference did not reach statistical significance, but the relative risk reduction was 93% (relative risks 0.07; 95% confidence interval (CI) 0.00 to 1.21). There was no difference in the length of hospital stay between the two groups (weighted mean difference 0.09 days; 95% CI -0.23 to 0.41). The data were too few and of insufficient quality to make any recommendations for practice. Future research on antibiotic prophylaxis for operative vaginal delivery is needed to conclude whether it is useful for reducing postpartum morbidity.

Continuous quality improvement in substance abuse treatment facilities: How much does it cost?

PubMed

Hunt, Priscillia; Hunter, Sarah B; Levan, Deborah

2017-06-01

Continuous quality improvement (CQI) has grown in the U.S. since the 1970s, yet little is known about the costs to implement CQI in substance abuse treatment facilities. This paper is part of a larger group randomized control trial in a large urban county evaluating the impact of Plan-Study-Do-Act (PDSA)-CQI designed for community service organizations (Hunter, Ober, Paddock, Hunt, & Levan, 2014). Operated by one umbrella organization, each of the eight facilities of the study, four residential and four outpatient substance abuse treatment facilities, selected their own CQI Actions, including administrative- and clinical care-related Actions. Using an activity-based costing approach, we collected labor and supplies and equipment costs directly attributable to CQI Actions over a 12-month trial period. Our study finds implementation of CQI and meeting costs of this trial per facility were approximately $2000 to $10,500 per year ($4500 on average), or $10 to $60 per admitted client. We provide a description of the sources of variation in these costs, including differing intensity of the CQI Actions selected, which should help decision makers plan use of PDSA-CQI. Copyright © 2017. Published by Elsevier Inc.

Treatment of first metatarsophalangeal joint arthritis using hemiarthroplasty with a synthetic cartilage implant or arthrodesis: A comparison of operative and recovery time.

PubMed

Glazebrook, Mark; Younger, Alastair S E; Daniels, Timothy R; Singh, Dishan; Blundell, Chris; de Vries, Gwyneth; Le, Ian L D; Nielsen, Dominic; Pedersen, M Elizabeth; Sakellariou, Anthony; Solan, Matthew; Wansbrough, Guy; Baumhauer, Judith F

2017-05-29

First metatarsophalangeal joint (MTPJ1) hemiarthroplasty using a novel synthetic cartilage implant was as effective and safe as MTPJ1 arthrodesis in a randomized clinical trial. We retrospectively evaluated operative time and recovery period for implant hemiarthroplasty (n=152) and MTPJ1 arthrodesis (n=50). Perioperative data were assessed for operative and anaesthesia times. Recovery and return to function were prospectively assessed with the Foot and Ankle Ability Measure (FAAM) Sports and Activities of Daily Living (ADL) subscales and SF-36 Physical Functioning (PF) subscore. Mean operative time for hemiarthroplasty was 35±12.3min and 58±21.5min for arthrodesis (p<0.001). Anaesthesia duration was 28min shorter with hemiarthroplasty (p<0.001). At weeks 2 and 6 postoperative, hemiarthroplasty patients demonstrated clinically and statistically significantly higher FAAM Sport, FAAM ADL, and SF-36 PF subscores versus arthrodesis patients. MTPJ1 hemiarthroplasty with a synthetic cartilage implant took less operative time and resulted in faster recovery than arthrodesis. III, Retrospective case control study. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Further Validation of the Pathways Housing First Fidelity Scale.

PubMed

Goering, Paula; Veldhuizen, Scott; Nelson, Geoffrey B; Stefancic, Ana; Tsemberis, Sam; Adair, Carol E; Distasio, Jino; Aubry, Tim; Stergiopoulos, Vicky; Streiner, David L

2016-01-01

This study examined whether Housing First fidelity ratings correspond to program operation descriptions from administrative data and predict client outcomes. A multisite, randomized controlled trial (At Home/Chez Soi) in five Canadian cities included two assessments of 12 programs over two years. Outcomes for 1,158 clients were measured every six months. Associations between fidelity ratings and administrative data (Spearman correlations) and participant outcomes (mixed-effects modeling) were examined. Fidelity ratings were generally good (mean ± SD=136.6 ± 10.3 out of a possible range of 38-152; 87% of maximum value). Fidelity was significantly associated with three of four measures of program operation, with correlations between .55 and .60. Greater program fidelity was associated with improvement in housing stability, community functioning, and quality of life. Variation in program fidelity was associated with operations and outcomes, supporting scale validity and intervention effectiveness. These findings reinforced the value of using fidelity monitoring to conduct quality assurance and technical assistance activities.

Preparation of the NASA Air Quality Monitor for a U.S. Navy Submarine Sea Trial

NASA Technical Reports Server (NTRS)

Limero, Thomas; Wallace, William T.; Manney, Joshua A.; Smith, Matthew J.; O'Connor, Sara Jane; Mudgett, Paul D.

2017-01-01

For the past 4 years, the Air Quality Monitor (AQM) has been the operational instrument for measuring trace volatile organic compounds on the International Space Station (ISS). The key components of the AQM are the inlet preconcentrator, the gas chromatograph (GC), and the differential mobility spectrometer. Onboard the ISS are two AQMs with different GC columns that detect and quantify 22 compounds. The AQM data contributes valuable information to the assessment of air quality aboard ISS for each crew increment. The US Navy is looking to update its submarine air monitoring suite of instruments and the success of the AQM on ISS has led to a jointly planned submarine sea trial of a NASA AQM. In addition to the AQM, the Navy is also interested in the Multi-Gas Monitor (MGM), which measures major constituent gases (oxygen, carbon dioxide, water vapor, and ammonia). A separate paper will present the MGM sea trial preparation and the analysis of most recent ISS data. A prototype AQM, which is virtually identical to the operational AQM, has been readied for the sea trial. Only one AQM will be deployed during the sea trial, but this is sufficient for NASA purposes and to detect the compounds of interest to the US Navy for this trial. The data from the sea trial will be compared to data from archival samples collected before, during, and after the trial period. This paper will start with a brief history of past collaborations between NASA and the U.S. and U.K. navies for trials of air monitoring equipment. An overview of the AQM technology and protocols for the submarine trial will be presented. The majority of the presentation will focus on the AQM preparation and a summary of available data from the trial.

The effectiveness of neuro-music therapy according to the Heidelberg model compared to a single session of educational counseling as treatment for tinnitus: a controlled trial.

PubMed

Argstatter, Heike; Grapp, Miriam; Hutter, Elisabeth; Plinkert, Peter K; Bolay, Hans-Volker

2015-03-01

Tinnitus is a very common symptom, yet the quest for an effective treatment is challenging. Results from several clinical trials support the notion that neuro-music therapy is an effective means to reduce tinnitus distress with short duration and long lasting effect. However, until now, the effectiveness has not been tested in a controlled trial against an active comparator. The trial was designed as two-center, parallel intervention group controlled study with two intervention groups: Counseling (50minute individualized personal instruction) or neuro-music therapy (counseling plus eight 50-minute sessions of individualized music therapy). Data of n=290 patients suffering from chronic tinnitus were analyzed. Outcome measure was the change in Tinnitus Questionnaire Total Scores (TQ) from baseline (admission) to end of treatment. Both treatment groups achieved a statistically relevant reduction in TQ scores, though 66% of patients in the music therapy group attained a clinically meaningful improvement compared to 33% in the counseling group. A binary logistic regression revealed two variables significantly influencing therapy outcome: initial tinnitus score and type of therapy with an OR for the music therapy compared to the counseling of 4.34 (CI 2.33-8.09). Counseling is an appropriate treatment option with well above chance of improvement. The neuro-music therapy outperformed the counseling. This treatment targets the tinnitus sound itself, is short in duration, intrinsically motivating and easy to operate and thus presents a possible complement to the therapeutic spectrum in chronic tinnitus. The trial was registered at the ClinicalTrials.gov registry (ID: NCT01845155). Copyright © 2014 Elsevier Inc. All rights reserved.

Traditionally vs sonographically coached pushing in second stage of labor: a pilot randomized controlled trial.

PubMed

Bellussi, F; Alcamisi, L; Guizzardi, G; Parma, D; Pilu, G

2018-03-13

To investigate the usefulness of visual biofeedback using transperineal ultrasound to improve coached pushing during the active second stage of labor in nulliparous women. This was a randomized controlled trial of low-risk nulliparous women in the active second stage of labor. Patients were allocated to either coached pushing aided by visual demonstration on transperineal ultrasound of the progress of the fetal head (sonographic coaching) or traditional coaching. Patients in both groups were coached by an obstetrician for the first 20 min of the active second stage of labor and, subsequently, the labor was supervised by a midwife. Primary outcomes were duration of the active second stage and increase in the angle of progression at the end of the coaching process. Secondary outcomes included the incidence of operative delivery and complications of labor. Forty women were recruited into the study. Those who received sonographic coaching had a shorter active phase of the second stage (30 min (interquartile range (IQR), 24-42 min) vs 45 min (IQR, 39-55 min); P = 0.01) and a greater increase in the angle of progression (13.5° (IQR, 9-20°) vs 5° (IQR, 3-9.5°); P = 0.01) in the first 20 min of the active second stage of labor than did those who had traditional coaching. No differences were found in the secondary outcomes between the two groups. Our preliminary data suggest that transperineal ultrasound may be a useful adjunct to coached pushing during the active second stage of labor. Further studies are required to confirm these findings and better define the benefits of this approach. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Efficacy of graded activity versus supervised exercises in patients with chronic non-specific low back pain: protocol of a randomised controlled trial

PubMed Central

2013-01-01

Background Low back pain is a relevant public health problem, being an important cause of work absenteeism worldwide, as well as affecting the quality of life of sufferers and their individual functional performances. Supervised active physical routines and of cognitive-behavioral therapies are recommended for the treatment of chronic Low back pain, although evidence to support the effectiveness of different techniques is missing. Accordingly, the aim of this study is to contrast the effectiveness of two types of exercises, graded activity or supervised, in decreasing symptoms of chronic low back pain. Methods/design Sample will consist of 66 patients, blindly allocated into one of two groups: 1) Graded activity which, based on an operant approach, will use time-contingent methods aiming to increase participants’ activity levels; 2) Supervised exercise, where participants will be trained for strengthening, stretching, and motor control targeting different muscle groups. Interventions will last one hour, and will happen twice a week for 6 weeks. Outcomes (pain, disability, quality of life, global perceived effect, return to work, physical activity, physical capacity, and kinesiophobia) will be assessed at baseline, at treatment end, and three and six months after treatment end. Data collection will be conducted by an investigator blinded to treatment allocation. Discussion This project describes the randomisation method that will be used to compare the effectiveness of two different treatments for chronic low back pain: graded activity and supervised exercises. Since optimal approach for patients with chronic back pain have yet not been defined based on evidence, good quality studies on the subject are necessary. Trial registration NCT01719276 PMID:23336703

Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis

PubMed Central

Monach, Paul A; Warner, Roscoe L; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Iklé, David; Kallenberg, Cees GM; Krischer, Jeffrey; Langford, Carol A; Mueller, Mark; Seo, Philip; St. Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Johnson, Kent J; Merkel, Peter A

2016-01-01

Objective To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation. Methods Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6 months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG)≥3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC). Results All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low. Conclusions Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV. PMID:22975753

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

PubMed

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

2016-09-08

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

Validation of the Diabetes Prevention Trial-Type 1 Risk Score in the TrialNet Natural History Study.

PubMed

Sosenko, Jay M; Skyler, Jay S; Mahon, Jeffrey; Krischer, Jeffrey P; Beam, Craig A; Boulware, David C; Greenbaum, Carla J; Rafkin, Lisa E; Cowie, Catherine; Cuthbertson, David; Palmer, Jerry P

2011-08-01

We assessed the accuracy of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), developed from the Diabetes Prevention Trial-Type 1 (DPT-1), in the TrialNet Natural History Study (TNNHS). Prediction accuracy of the DPTRS was assessed with receiver-operating characteristic curve areas. The type 1 diabetes cumulative incidence within the DPTRS intervals was compared between the TNNHS and DPT-1 cohorts. Receiver-operating characteristic curve areas for the DPTRS were substantial in the TNNHS (P < 0.001 at both 2 and 3 years). The type 1 diabetes cumulative incidence did not differ significantly between the TNNHS and DPT-1 cohorts within DPTRS intervals. In the TNNHS, 2-year and 3-year risks were low for DPTRS intervals <6.50 (<0.10 and <0.20, respectively). Thresholds ≥7.50 were indicative of high risk in both cohorts (2-year risks: 0.49 in the TNNHS and 0.51 in DPT-1). The DPTRS is an accurate and robust predictor of type 1 diabetes in autoantibody-positive populations.

A review of current surgical practice in the operative treatment of proximal humeral fractures

PubMed Central

Jones, L. D.; Palmer, A. J. R.; Macnair, R. D.; Brewer, P. E.; Jayadev, C.; Wheelton, A. N.; Ball, D. E. J.; Nandra, R. S.; Aujla, R. S.; Sykes, A. E.; Carr, A. J.

2016-01-01

Objectives The PROximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial has recently demonstrated that surgery is non-superior to non-operative treatment in the management of displaced proximal humeral fractures. The objective of this study was to assess current surgical practice in the context of the PROFHER trial in terms of patient demographics, injury characteristics and the nature of the surgical treatment. Methods A total of ten consecutive patients undergoing surgery for the treatment of a proximal humeral fracture from each of 11 United Kingdom hospitals were retrospectively identified over a 15 month period between January 2014 and March 2015. Data gathered for the 110 patients included patient demographics, injury characteristics, mode of surgical fixation, the grade of operating surgeon and the cost of the surgical implants. Results A majority of the patients were female (66%, 73 of 110). The mean patient age was 62 years (range 18 to 89). A majority of patients met the inclusion criteria for the PROFHER trial (75%, 83 of 110). Plate fixation was the most common mode of surgery (68%, 75 patients), followed by intramedullary fixation (12%, 13 patients), reverse shoulder arthroplasty (10%, 11 patients) and hemiarthroplasty (7%, eight patients). The consultant was either the primary operating surgeon or supervising the operating surgeon in a large majority of cases (91%, 100 patients). Implant costs for plate fixation were significantly less than both hemiarthroplasty (p < 0.05) and reverse shoulder arthroplasty (p < 0.0001). Implant costs for intramedullary fixation were significantly less than plate fixation (p < 0.01), hemiarthroplasty (p < 0.0001) and reverse shoulder arthroplasty (p < 0.0001). Conclusions Our study has shown that the majority of a representative sample of patients currently undergoing surgical treatment for a proximal humeral fracture in these United Kingdom centres met the inclusion criteria for the PROFHER trial and that a proportion of these patients may, therefore, have been effectively managed non-operatively. Cite this article: Mr B. J. F. Dean. A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change? Bone Joint Res 2016;5:178–184. DOI: 10.1302/2046-3758.55.2000596. PMID:27179004

Barriers and Solutions to Smart Water Grid Development.

PubMed

Cheong, So-Min; Choi, Gye-Woon; Lee, Ho-Sun

2016-03-01

This limited review of smart water grid (SWG) development, challenges, and solutions provides an initial assessment of early attempts at operating SWGs. Though the cost and adoption issues are critical, potential benefits of SWGs such as efficient water conservation and distribution sustain the development of SWGs around the world. The review finds that the keys to success are the new regulations concerning data access and ownership to solve problems of security and privacy; consumer literacy to accept and use SWGs; active private sector involvement to coordinate SWG development; government-funded pilot projects and trial centers; and integration with sustainable water management.

Barriers and Solutions to Smart Water Grid Development

NASA Astrophysics Data System (ADS)

Cheong, So-Min; Choi, Gye-Woon; Lee, Ho-Sun

2016-03-01

This limited review of smart water grid (SWG) development, challenges, and solutions provides an initial assessment of early attempts at operating SWGs. Though the cost and adoption issues are critical, potential benefits of SWGs such as efficient water conservation and distribution sustain the development of SWGs around the world. The review finds that the keys to success are the new regulations concerning data access and ownership to solve problems of security and privacy; consumer literacy to accept and use SWGs; active private sector involvement to coordinate SWG development; government-funded pilot projects and trial centers; and integration with sustainable water management.

Aspirin Use Prior to Coronary Artery Bypass Grafting Surgery: a Systematic Review.

PubMed

Elbadawi, Ayman; Saad, Marwan; Nairooz, Ramez

2017-02-01

Aspirin use before coronary artery bypass graft (CABG) surgery has been a puzzling question for years. Controversy existed regarding the overall benefits vs. risk of pre-operative aspirin use and was translated to conflicting guidelines from major societies. Observational studies have suggested a reduced mortality with pre-operative aspirin use. A meta-analysis of randomized controlled trials showed increased risk of post-operative bleeding with aspirin, with no associated increased mortality risk. A recent large randomized controlled trial did not find a significant difference in bleeding risk or post-operative mortality with pre-CABG aspirin use. The results of available studies showed a beneficial effect with pre-CABG aspirin use by decreasing thrombotic complications and perioperative myocardial infarction, with an associated adverse risk of bleeding that did not affect mortality rates. Given overall benefit-risk assessment, we are in favor of pre-operative aspirin use in CABG patients.

Withholding a Reward-driven Action: Studies of the Rise and Fall of Motor Activation and the Effect of Cognitive Depletion.

PubMed

Freeman, Scott M; Aron, Adam R

2016-02-01

Controlling an inappropriate response tendency in the face of a reward-predicting stimulus likely depends on the strength of the reward-driven activation, the strength of a putative top-down control process, and their relative timing. We developed a rewarded go/no-go paradigm to investigate such dynamics. Participants made rapid responses (on go trials) to high versus low reward-predicting stimuli and sometimes had to withhold responding (on no-go trials) in the face of the same stimuli. Behaviorally, for high versus low reward stimuli, responses were faster on go trials, and there were more errors of commission on no-go trials. We used single-pulse TMS to map out the corticospinal excitability dynamics, especially on no-go trials where control is needed. For successful no-go trials, there was an early rise in motor activation that was then sharply reduced beneath baseline. This activation-reduction pattern was more pronounced for high- versus low-reward trials and in individuals with greater motivational drive for reward. A follow-on experiment showed that, when participants were fatigued by an effortful task, they made more errors on no-go trials for high versus low reward stimuli. Together, these studies show that, when a response is inappropriate, reward-predicting stimuli induce early motor activation, followed by a top-down effortful control process (which we interpret as response suppression) that depends on the strength of the preceding activation. Our findings provide novel information about the activation-suppression dynamics during control over reward-driven actions, and they illustrate how fatigue or depletion leads to control failures in the face of reward.

Working memory for vibrotactile frequencies: comparison of cortical activity in blind and sighted individuals.

PubMed

Burton, Harold; Sinclair, Robert J; Dixit, Sachin

2010-11-01

In blind, occipital cortex showed robust activation to nonvisual stimuli in many prior functional neuroimaging studies. The cognitive processes represented by these activations are not fully determined, although a verbal recognition memory role has been demonstrated. In congenitally blind and sighted (10 per group), we contrasted responses to a vibrotactile one-back frequency retention task with 5-s delays and a vibrotactile amplitude-change task; both tasks involved the same vibration parameters. The one-back paradigm required continuous updating for working memory (WM). Findings in both groups confirmed roles in WM for right hemisphere dorsolateral prefrontal (DLPFC) and dorsal/ventral attention components of posterior parietal cortex. Negative findings in bilateral ventrolateral prefrontal cortex suggested task performance without subvocalization. In bilateral occipital cortex, blind showed comparable positive responses to both tasks, whereas WM evoked large negative responses in sighted. Greater utilization of attention resources in blind were suggested as causing larger responses in dorsal and ventral attention systems, right DLPFC, and persistent responses across delays between trials in somatosensory and premotor cortex. In sighted, responses in somatosensory and premotor areas showed iterated peaks matched to stimulation trial intervals. The findings in occipital cortex of blind suggest that tactile activations do not represent cognitive operations for nonverbal WM task. However, these data suggest a role in sensory processing for tactile information in blind that parallels a similar contribution for visual stimuli in occipital cortex of sighted. © 2010 Wiley-Liss, Inc.

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

PubMed Central

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

2008-01-01

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

Peri-operative anaesthetic myocardial preconditioning and protection – cellular mechanisms and clinical relevance in cardiac anaesthesia

PubMed Central

Kunst, G; Klein, A A

2015-01-01

Preconditioning has been shown to reduce myocardial damage caused by ischaemia–reperfusion injury peri-operatively. Volatile anaesthetic agents have the potential to provide myocardial protection by anaesthetic preconditioning and, in addition, they also mediate renal and cerebral protection. A number of proof-of-concept trials have confirmed that the experimental evidence can be translated into clinical practice with regard to postoperative markers of myocardial injury; however, this effect has not been ubiquitous. The clinical trials published to date have also been too small to investigate clinical outcome and mortality. Data from recent meta-analyses in cardiac anaesthesia are also not conclusive regarding intra-operative volatile anaesthesia. These inconclusive clinical results have led to great variability currently in the type of anaesthetic agent used during cardiac surgery. This review summarises experimentally proposed mechanisms of anaesthetic preconditioning, and assesses randomised controlled clinical trials in cardiac anaesthesia that have been aimed at translating experimental results into the clinical setting. PMID:25764404

Global women's health: current clinical trials in low- and middle-income countries.

PubMed

Merriel, A; Harb, H M; Williams, H; Lilford, R; Coomarasamy, A

2015-01-01

Clinical trials in low- and middle-income countries (LMICs) are necessary to develop evidence-based approaches to improve women's health. Understanding what research is currently being conducted will allow the identification of research gaps, avoidance of duplication, planning of future studies, collaboration amongst research groups, and geographical targeting for research investments. To provide an overview of active women's health trials in LMICs. The World Health Organization's International Clinical Trials Registry Platform was searched for trials registered between 1 April 2012 and 31 March 2014. Selected trials were randomised, conducted in LMICs, active, and with a women's health intervention or a significant outcome for the woman. Two reviewers extracted data. Analysis included geographical spread, speciality areas, pre-enrolment registration, study size, and funders. Of the 8966 records, 509 were eligible for inclusion. Gynaecology trials made up 57% of the research, whereas the remaining 43% of trials were in obstetrics. Research activity focused on fertility (17%), the antenatal period (15%), benign gynaecology (14%), intrapartum care (9%), and pre-invasive disease and cancers (8%). The majority of trials (84%) took place in middle-income countries (MICs). In low-income countries (LICs) 83% of research investigated obstetrics, and in MICs 60% of research investigated gynaecology. Most trials (80%) had a sample size of 500 or fewer participants. The median size of trials in LICs was 815 compared with 128 in MICs. Pre-enrolment registration occurred in 54% of trials. The majority (62%) of trials were funded locally. Many LMICs are active in women's health research. The majority of registered trials are located in MICs; however, the trials in LICs are often larger. The focus of research in MICs may be driven by local priorities and funding, with fertility being highly researched. In LICs, pregnancy is the focus, perhaps reflecting the international prioritisation of maternal health. © 2014 Royal College of Obstetricians and Gynaecologists.

POSITIVE study: physical exercise program in non-operable lung cancer patients undergoing palliative treatment.

PubMed

Wiskemann, Joachim; Hummler, Simone; Diepold, Christina; Keil, Melanie; Abel, Ulrich; Steindorf, Karen; Beckhove, Philipp; Ulrich, Cornelia M; Steins, Martin; Thomas, Michael

2016-07-19

Patients with advanced stage non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) often experience multidimensional impairments, affecting quality of life during their course of disease. In lung cancer patients with operable disease, several studies have shown that exercise has a positive impact on quality of life and physical functioning. There is limited evidence regarding efficacy for advanced lung cancer patients undergoing palliative treatment. Therefore, the POSITIVE study aims to evaluate the benefit of a 24-week exercise intervention during palliative treatment in a randomized controlled setting. The POSITIVE study is a randomized, controlled trial investigating the effects of a 24-week exercise intervention during palliative treatment on quality of life, physical performance and immune function in advanced, non-operable lung cancer patients. 250 patients will be recruited in the Clinic for Thoracic Diseases in Heidelberg, enrolment begun in November 2013. Main inclusion criterion is histologically confirmed NSCLC (stage IIIa, IIIb, IV) or SCLC (Limited Disease-SCLC, Extensive Disease-SCLC) not amenable to surgery. Patients are randomized into two groups. Both groups receive weekly care management phone calls (CMPCs) with the goal to assess symptoms and side effects. Additionally, one group receives a combined resistance and endurance training (3x/week). Primary endpoints are quality of life assessed by the Functional Assessment of Cancer Therapy for patients with lung cancer (FACT-L, subcategory Physical Well-Being) and General Fatigue measured by the Multidimensional Fatigue Inventory (MFI-20). Secondary endpoints are physical performance (maximal voluntary isometric contraction, 6-min walk distance), psychosocial (depression and anxiety) and immunological parameters and overall survival. The aim of the POSITIVE trial is the evaluation of effects of a 24-week structured and guided exercise intervention during palliative treatment stages. Analysis of various outcomes (such as quality of life, physical performance, self-efficacy, psychosocial and immunological parameters) will contribute to a better understanding of the potential of exercise in advanced lung cancer patients. In contrast to other studies with advanced oncological patients the POSITIVE trial provides weekly phone calls to support patients both in the intervention and control group and to segregate the impact of physical activity on quality of life. ClinicalTrials.gov NCT02055508 (Date: December 12, 2013).

Can exergaming contribute to improving physical activity levels and health outcomes in children?

PubMed

Daley, Amanda J

2009-08-01

Physical inactivity among children is a serious public health problem. It has been suggested that high levels of screen time are contributory factors that encourage sedentary lifestyles in young people. As physical inactivity and obesity levels continue to rise in young people, it has been proposed that new-generation active computer- and video-console games (otherwise known as "exergaming") may offer the opportunity to contribute to young people's energy expenditure during their free time. Although studies have produced some encouraging results regarding the energy costs involved in playing active video-console games, the energy costs of playing the authentic versions of activity-based video games are substantially larger, highlighting that active gaming is no substitute for real sports and activities. A small number of exergaming activities engage children in moderate-intensity activity, but most do not. Only 3 very small trials have considered the effects of exergaming on physical activity levels and/or other health outcomes in children. Evidence from these trials has been mixed; positive trends for improvements in some health outcomes in the intervention groups were noted in 2 trials. No adequately powered randomized, controlled trial has been published to date, and no trial has assessed the long-term impact of exergaming on children's health. We now need high-quality randomized, controlled trials to evaluate the effectiveness and sustainability of exergaming, as well as its clinical relevance; until such studies take place, we should remain cautious about its ability to positively affect children's health.

Complete Report on the Development of Welding Parameters for Irradiated Materials

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

Frederick, Greg; Sutton, Benjamin J.; Tatman, Jonathan K.

The advanced welding facility at the Radiochemical Engineering Development Center of Oak Ridge National Laboratory, which was conceived to enable research and development of weld repair techniques for nuclear power plant life extension, is now operational. The development of the facility and its advanced welding capabilities, along with the model materials for initial welding trials, were funded jointly by the U.S. Department of Energy, Office of Nuclear Energy, Light Water Reactor Sustainability Program, the Electric Power Research Institute, Long Term Operations Program and the Welding and Repair Technology Center, with additional support from Oak Ridge National Laboratory. Welding of irradiatedmore » materials was initiated on November 17, 2017, which marked a significant step in the development of the facility and the beginning of extensive welding research and development campaigns on irradiated materials that will eventually produce validated techniques and guidelines for weld repair activities carried out to extend the operational lifetimes of nuclear power plants beyond 60 years. This report summarizes the final steps that were required to complete weld process development, initial irradiated materials welding activities, near-term plans for irradiated materials welding, and plans for post-weld analyses that will be carried out to assess the ability of the advanced welding processes to make repairs on irradiated materials.« less

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

Effectiveness of an intervention to facilitate the implementation of healthy eating and physical activity policies and practices in childcare services: a randomised controlled trial.

PubMed

Jones, Jannah; Wyse, Rebecca; Finch, Meghan; Lecathelinais, Christophe; Wiggers, John; Marshall, Josephine; Falkiner, Maryann; Pond, Nicole; Yoong, Sze Lin; Hollis, Jenna; Fielding, Alison; Dodds, Pennie; Clinton-McHarg, Tara; Freund, Megan; McElduff, Patrick; Gillham, Karen; Wolfenden, Luke

2015-10-25

The primary aim of this study was to evaluate the effectiveness of an intervention to increase the implementation of healthy eating and physical activity policies and practices by centre-based childcare services. The study also sought to determine if the intervention was effective in improving child dietary intake and increasing child physical activity levels while attending childcare. A parallel group, randomised controlled trial was conducted in a sample of 128 childcare services. Intervention strategies included provision of implementation support staff, securing executive support, staff training, consensus processes, academic detailing visits, tools and resources, performance monitoring and feedback and a communications strategy. The primary outcome of the trial was the proportion of services implementing all seven healthy eating and physical activity policies and practices targeted by the intervention. Outcome data were collected via telephone surveys with nominated supervisors and room leaders at baseline and immediately post-intervention. Secondary trial outcomes included the differences between groups in the number of serves consumed by children for each food group within the Australian Guide to Healthy Eating and in the proportion of children engaged in sedentary, walking or very active physical activity assessed via observation in a random subsample of 36 services at follow-up. There was no significant difference between groups for the primary trial outcome (p = 0.44). Relative to the control group, a significantly larger proportion of intervention group services reported having a written nutrition and physical activity policy (p = 0.05) and providing adult-guided activities to develop fundamental movement skills (p = 0.01). There were no significant differences between groups at follow-up on measures of child dietary intake or physical activity. The findings of the trial were equivocal. While there was no significant difference between groups for the primary trial outcome, the intervention did significantly increase the proportion of intervention group services implementing two of the seven healthy eating and physical activity policies and practices. High levels of implementation of a number of policies and practices at baseline, significant obesity prevention activity in the study region and higher than previously reported intra-class correlation of child behaviours may, in part, explain the trial findings. Australian Clinical Trials Registry (reference ACTRN12612000927820 ).

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

PubMed

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

2016-07-01

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

Understanding the investigators: a qualitative study investigating the barriers and enablers to the implementation of local investigator-initiated clinical trials in Ethiopia

PubMed Central

Franzen, Samuel R P; Chandler, Clare; Enquselassie, Fikre; Siribaddana, Sisira; Atashili, Julius; Angus, Brian; Lang, Trudie

2013-01-01

Objectives Clinical trials provide ‘gold standard’ evidence for policy, but insufficient locally relevant trials are conducted in low-income and middle-income countries. Local investigator-initiated trials could generate highly relevant data for national governments, but information is lacking on how to facilitate them. We aimed to identify barriers and enablers to investigator-initiated trials in Ethiopia to inform and direct capacity strengthening initiatives. Design Exploratory, qualitative study comprising of in-depth interviews (n=7) and focus group discussions (n=3). Setting Fieldwork took place in Ethiopia during March 2011. Participants Local health researchers with previous experiences of clinical trials or stakeholders with an interest in trials were recruited through snowball sampling (n=20). Outcome measures Detailed discussion notes were analysed using thematic coding analysis and key themes were identified. Results All participants perceived investigator-initiated trials as important for generating local evidence. System and organisational barriers included: limited funding allocation, weak regulatory and administrative systems, few learning opportunities, limited human and material capacity and poor incentives for conducting research. Operational hurdles were symptomatic of these barriers. Lack of awareness, confidence and motivation to undertake trials were important individual barriers. Training, knowledge sharing and experience exchange were key enablers to trial conduct and collaboration was unanimously regarded as important for improving capacity. Conclusions Barriers to trial conduct were found at individual, operational, organisational and system levels. These findings indicate that to increase locally led trial conduct in Ethiopia, system wide changes are needed to create a more receptive and enabling research environment. Crucially, the creation of research networks between potential trial groups could provide much needed practical collaborative support through sharing of financial and project management burdens, knowledge and resources. These findings could have important implications for capacity-strengthening initiatives but further research is needed before the results can be generalised more widely. PMID:24285629

Active versus passive maintenance of visual nonverbal memory.

PubMed

McKeown, Denis; Holt, Jessica; Delvenne, Jean-Francois; Smith, Amy; Griffiths, Benjamin

2014-08-01

Forgetting over the short term has challenged researchers for more than a century, largely because of the difficulty of controlling what goes on within the memory retention interval. But the "recent-negative-probe" procedure offers a valuable paradigm, by examining the influences of (presumably) unattended memoranda from prior trials. Here we used a recent-probe task to investigate forgetting for visual nonverbal short-term memory. The target stimuli (two visually presented abstract shapes) on a trial were followed after a retention interval by a probe, and participants indicated whether the probe matched one of the target items. Proactive interference, and hence memory for old trial probes, was observed, whereby participants were slowed in rejecting a nonmatching probe on the current trial that nevertheless matched a target item on the previous trial (a recent-negative probe). The attraction of the paradigm is that, by uncovering proactive influences of past-trial probe stimuli, it can be argued that active maintenance in memory of those probes is unlikely. In two experiments, we recorded such proactive interference of prior-trial items over a range of interstimulus (ISI) and intertrial (ITI) intervals (between 1 and 6 s, respectively). Consistent with a proposed two-process memory conception (the active-passive memory model, or APM), actively maintained memories on current trials decayed, but passively "maintained," or unattended, visual memories of stimuli on past trials did not.

[Concept and results of the German Research Network on Schizophrenia].

PubMed

Gaebel, W; Buchkremer, G; Häfner, H; Klosterkötter, J; Maier, W; Möller, H-J; Wölwer, W

2016-04-01

The German Research Network on Schizophrenia (GRNS) was funded by the Federal Ministry of Education and Research (BMBF) from 1999 to 2011. The aim was to obtain a better horizontal and vertical networking of German research and care facilities on schizophrenia, in order to investigate open research questions, to transfer the results into clinical practice and improve care and quality of life in patients with schizophrenia. This paper describes the concept and operations of the GRNS as well as its results on the basis of selected research projects. The GRNS comprised about 25 clinical trials of high practical relevance, which were closely interrelated regarding content, methodology and organization. The trials primarily served the development and evaluation of new and established diagnostic and therapeutic approaches, the assessment of the status quo of clinical care, as well as its improvements, together with the investigation of basic scientific questions. Many substantial results to highly relevant issues were obtained, which led or will lead to an improvement in mental health care. Quantitative and qualitative evaluation parameters, such as scientific publications and obtaining additional grants, as well as promotion of young scientists, public relations activities, congress activities and the foundation of a European Schizophrenia Association, document the successful work of the network. Successful funding requests will allow us to continue cooperative schizophrenia research in Germany as initiated by the GRNS, without necessarily always binding these activities formally to the GRNS.

The intervention process in the European Fans in Training (EuroFIT) trial: a mixed method protocol for evaluation.

PubMed

van de Glind, I; Bunn, C; Gray, C M; Hunt, K; Andersen, E; Jelsma, J; Morgan, H; Pereira, H; Roberts, G; Rooksby, J; Røynesdal, Ø; Silva, M; Sorensen, M; Treweek, S; van Achterberg, T; van der Ploeg, H; van Nassau, F; Nijhuis-van der Sanden, M; Wyke, S

2017-07-27

EuroFIT is a gender-sensitised, health and lifestyle program targeting physical activity, sedentary time and dietary behaviours in men. The delivery of the program in football clubs, led by the clubs' community coaches, is designed to both attract and engage men in lifestyle change through an interest in football or loyalty to the club they support. The EuroFIT program will be evaluated in a multicentre pragmatic randomised controlled trial (RCT), for which ~1000 overweight men, aged 30-65 years, will be recruited in 15 top professional football clubs in the Netherlands, Norway, Portugal and the UK. The process evaluation is designed to investigate how implementation within the RCT is achieved in the various football clubs and countries and the processes through which EuroFIT affects outcomes. This mixed methods evaluation is guided by the Medical Research Council (MRC) guidance for conducting process evaluations of complex interventions. Data will be collected in the intervention arm of the EuroFIT trial through: participant questionnaires (n = 500); attendance sheets and coach logs (n = 360); observations of sessions (n = 30); coach questionnaires (n = 30); usage logs from a novel device for self-monitoring physical activity and non-sedentary behaviour (SitFIT); an app-based game to promote social support for physical activity outside program sessions (MatchFIT); interviews with coaches (n = 15); football club representatives (n = 15); and focus groups with participants (n = 30). Written standard operating procedures are used to ensure quality and consistency in data collection and analysis across the participating countries. Data will be analysed thematically within datasets and overall synthesis of findings will address the processes through which the program is implemented in various countries and clubs and through which it affects outcomes, with careful attention to the context of the football club. The process evaluation will provide a comprehensive account of what was necessary to implement the EuroFIT program in professional football clubs within a trial setting and how outcomes were affected by the program. This will allow us to re-appraise the program's conceptual base, optimise the program for post-trial implementation and roll out, and offer suggestions for the development and implementation of future initiatives to promote health and wellbeing through professional sports clubs. ISRCTN81935608 . Registered on 16 June 2015.

Mild to moderate dehydration combined with moderate alcohol consumption has no influence on simulated driving performance.

PubMed

Irwin, Christopher; Leveritt, Michael; Shum, David H K; Desbrow, Ben

2014-01-01

Many people consume alcoholic beverages following a period of physical activity that results in fluid loss through sweating (e.g., after sports, work). Adequate rehydration following physical activity may not occur, consequently resulting in the consumption of alcohol in a dehydrated state. This may have serious implications for the safety of individuals operating motor vehicles. Therefore, this study investigated the impact of mild-moderate dehydration in combination with moderate alcohol consumption on simulated driving performance. Fourteen healthy males participated in a placebo-controlled crossover design study involving 4 experimental trials (separated by 4 days or more). In each trial, participants were dehydrated by ∼2 percent body mass through exercise. After a 30-min recovery, participants completed a 15-min computerized simulated driving task (drive 1). In 2 of the trials, participants were provided with water equivalent to either 50 or 150 percent body mass loss and also received salt capsules (NaCl, 50 mmol/L). A set volume of alcohol or placebo was then consumed in each trial, incorporating the conditions: dehydration-placebo (DP), dehydration-alcohol (DA), partial rehydration-alcohol (PA), and full rehydration-alcohol (FA). The volume of the alcoholic beverage was individually calculated and intended to raise the blood alcohol content (BAC) to ∼0.05 percent. The same driving task was then readministered (drive 2). Primary outcome measures of driving consisted of standard deviation of lateral position (SDLP), number of side and center line crossings (LC), number of failures to stop at red traffic signals (FTS), number of impacts/collisions with other vehicles or objects (IMP), and time to collision with a specified lead vehicle (TTC). In addition, reaction time (RT) and incorrect inhibition response (IIR) behavior to critical events were collected throughout each experimental drive. Subjective ratings of mood and estimates of alcohol intoxication and driving impairment were also recorded in each trial. No effects of trial condition were observed on any of the driving performance measures or on subjective ratings of mood, alcohol intoxication, and driving impairment. SDLP was higher following the consumption of alcohol compared to the placebo trial. However, no differences in SDLP were recorded between the alcohol trials, indicating that hydration level had no observable interaction with alcohol to influence SDLP performance. Overall, it appears that dehydration does not exacerbate impairment in driving performance caused by mild-moderate alcohol intoxication. Further research is required to clarify the effects of alcohol and dehydration at various alcohol doses.

Intra-abdominal saline irrigation at cesarean section: a systematic review and meta-analysis.

PubMed

Eke, Ahizechukwu Chigoziem; Shukr, Ghadear Hussein; Chaalan, Tina Taissir; Nashif, Sereen Khaled; Eleje, George Uchenna

2016-01-01

The aim of this study was to examine the evidence guiding intraoperative saline irrigation at cesarean sections. We searched "cesarean sections", "pregnancy", "saline irrigation" and "randomized clinical trials" in ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, AJOL, MEDLINE, LILACS and CINAHL from inception of each database to April 2015. The primary outcomes were predefined as intraoperative nausea and emesis. The pooled results were reported as relative risk (RR) with 95% confidence interval (95% CI). Three randomized trials including 862 women were analyzed. Intraoperative saline irrigation was associated with a 68% increased risk of developing intraoperative nausea (RR = 1.68, 95% CI 1.36-2.06), 70% increased risk of developing intraoperative emesis (RR = 1.70, 95% CI 1.28-2.25), 92% increased risk of developing post-operative nausea and 84% increased risk of using anti-emetics post-operatively (RR = 1.84, 95% CI 0.21-2.78) when compared with controls. There were no significant differences between intraoperative saline irrigation and no treatment for post-operative emesis (RR = 1.65, 95% CI 0.74-3.67), estimated blood loss, time to return of gastrointestinal function, postpartum endometritis (RR = 0.95, 95% CI 0.64-1.40), urinary tract infection and wound infection. Intraoperative saline irrigation at cesarean delivery increases intraoperative and post-operative nausea, requiring increasing use of anti-emetics without significant reduction in infectious, intraoperative and postpartum complications. Routine abdominal irrigation at cesarean section is not supported by current data.

Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Subarachnoid hemorrhage is a common and dangerous disease with an unfavorable prognosis. Patients with poor-grade subarachnoid hemorrhage (Hunt & Hess Grades 4–5) are unconscious on admission. Because of the high mortality and disability rate associated with poor-grade subarachnoid hemorrhage, it is often treated conservatively. Timing of surgery for poor-grade aneurysmal subarachnoid hemorrhage is still controversial, therefore this study aims to identify the optimal time to operate on patients admitted in poor clinical condition. Methods/design Ninety-nine patients meeting the inclusion criteria were randomly assigned into three treatment groups. The early surgery group received operation within 3 days after onset of subarachnoid hemorrhage (day of SAH = day 1); the intermediate surgery group received operation from days 4 to 7, and surgery was performed on the late surgery group after day 7. Follow-up was performed 1, 3, and 6 months after aneurysm clipping. Primary indicators of outcome included the Extended Glasgow Outcome Scale and the Modified Rankin Scale, while secondary indicators of outcome were assessed using the Barthel Index and mortality. Discussion This is the first prospective, single-center, observer-blinded, randomized controlled trial to elucidate optimal timing for surgery in poor-grade subarachnoid hemorrhage patients. The results of this study will be used to direct decisions of surgical intervention in poor-grade subarachnoid hemorrhage, thus improving clinical outcomes for patients. Trial registration Chinese Clinical Trial Registry: ChiCTR-TRC-12002917 PMID:23957458

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).

Optimal weighted averaging of event related activity from acquisitions with artifacts.

PubMed

Vollero, Luca; Petrichella, Sara; Innello, Giulio

2016-08-01

In several biomedical applications that require the signal processing of biological data, the starting procedure for noise reduction is the ensemble averaging of multiple repeated acquisitions (trials). This method is based on the assumption that each trial is composed of two additive components: (i) a time-locked activity related to some sensitive/stimulation phenomenon (ERA, Event Related Activity in the following) and (ii) a sum of several other non time-locked background activities. The averaging aims at estimating the ERA activity under very low Signal to Noise and Interference Ratio (SNIR). Although averaging is a well established tool, its performance can be improved in the presence of high-power disturbances (artifacts) by a trials classification and removal stage. In this paper we propose, model and evaluate a new approach that avoids trials removal, managing trials classified as artifact-free and artifact-prone with two different weights. Based on the model, a weights tuning is possible and through modeling and simulations we show that, when optimally configured, the proposed solution outperforms classical approaches.

Less deep vein thrombosis due to transcutaneous fibular nerve stimulation in total knee arthroplasty: a randomized controlled trial.

PubMed

Izumi, Masashi; Ikeuchi, Masahiko; Aso, Koji; Sugimura, Natsuki; Kamimoto, Yuko; Mitani, Tetsuya; Ueta, Tadashi; Sato, Takayuki; Yokoyama, Masataka; Sugiura, Tetsuro; Tani, Toshikazu

2015-11-01

It has been known for years that deep vein thrombi (DVT) start to develop during total joint arthroplasty. Previously, we reported effective prevention of venous stasis by transcutaneous electrical nerve stimulation (TENS). It is hypothesized that TENS might be a thromboprophylactic tool for the limb undergoing surgery. The purpose of this study is to clarify the clinical efficacy and safety of TENS in patients during total knee arthroplasty (TKA). Ninety patients undergoing primary TKA were involved and randomly allocated to the TENS or control group. In the TENS group, electrical stimulation of the common fibular nerve, which produced a brisk dorsiflexion of the ankle, was performed for the operated leg during surgery. In the control group, no electrical stimulation was applied. Serum D-dimer and soluble fibrin monomer complex (SFMC) levels were measured before surgery, immediately after surgery, and post-operative day (POD) 1. Ultrasonography was performed on POD 1. Immediately after surgery, D-dimer and SFMC levels of each group were significantly lower in the TENS group compared with control (p < 0.05). The incidence of DVT was 11 % (five cases) in the TENS group while 31 % (14 cases) in control (p = 0.02). There were no adverse effects related to TENS. TENS during TKA showed significant effects on preventing DVT. Sustaining muscle pump activation during surgery prevented not only venous stasis, but also hypercoagulability of blood. Intraoperative TENS is a safe and novel strategy against early post-operative thromboembolism, which is difficult to be completed through existing prophylaxis after total joint arthroplasty. Randomized controlled trial, Level I.

Persistent occiput posterior: OUTcomes following digital rotation: a pilot randomised controlled trial.

PubMed

Graham, Kathryn; Phipps, Hala; Hyett, Jon A; Ludlow, Joanne P; Mackie, Adam; Marren, Anthony; De Vries, Bradley

2014-06-01

To determine the feasibility of a multicentre randomised controlled trial (RCT) to investigate whether digital rotation of the fetal head from occiput posterior (OP) position in the second stage of labour reduces the risk of operative delivery (defined as caesarean section (CS) or instrumental delivery). We conducted the study between December 2010 and December 2011 in a tertiary referral hospital in Australia. A transabdominal ultrasound was performed early in the second stage of labour on women with cephalic, singleton pregnancies to determine the fetal position. Those women with a fetus in the OP position were randomised to either a digital rotation or a sham procedure. In all other ways, participants received their usual intrapartum care. Data regarding demographics, mode of delivery, labour, post natal period and neonatal outcomes were collected. One thousand and four women were consented, 834 achieved full dilatation, and 30 were randomised. An additional portable ultrasound scan and a blinded 'sham' digital rotation were acceptable to women and staff. Operative delivery rates were 13/15 in the digital rotation (four CS and nine instrumental) and 12/15 in the sham (three CS and nine instrumental) groups, respectively. A large double-blinded multicentre RCT would be feasible and acceptable to women and staff. Strategies to improve recruitment such as consenting women with an effective epidural in active labour should be considered. This would be the first RCT to answer a clinically important question which could significantly affect the operative delivery rate in Australia and internationally. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Promoting physical activity: development and testing of self-determination theory-based interventions

PubMed Central

2012-01-01

A growing number of studies have pulled from Deci and Ryan's Self-Determination Theory to design interventions targeting health behavior change. More recently, researchers have begun using SDT to promote the adoption and maintenance of an active lifestyle. In this review, we aim to highlight how researchers and practitioners can draw from the SDT framework to develop, implement, and evaluate intervention efforts centered on increasing physical activity levels in different contexts and different populations. In the present paper, the rationale for using SDT to foster physical activity engagement is briefly reviewed before particular attention is given to three recent randomized controlled trials, the Canadian Physical Activity Counseling (PAC) Trial, the Empower trial from the UK, and the Portuguese PESO (Promotion of Health and Exercise in Obesity) trial, each of which focused on promoting physical activity behavior. The SDT-based intervention components, procedures, and participants are highlighted, and the key findings that have emanated from these three trials are presented. Lastly, we outline some of the limitations of the work conducted to date in this area and we acknowledge the challenges that arise when attempting to design, deliver, and test SDT-grounded interventions in the context of physical activity promotion. PMID:22385751

Non-operative management versus operative management in high-grade blunt hepatic injury.

PubMed

Cirocchi, Roberto; Trastulli, Stefano; Pressi, Eleonora; Farinella, Eriberto; Avenia, Stefano; Morales Uribe, Carlos Hernando; Botero, Ana Maria; Barrera, Luis M

2015-08-24

Surgery used to be the treatment of choice in cases of blunt hepatic injury, but this approach gradually changed over the last two decades as increasing non-operative management (NOM) of splenic injury led to its use for hepatic injury. The improvement in critical care monitoring and computed tomographic scanning, as well as the more frequent use of interventional radiology techniques, has helped to bring about this change to non-operative management. Liver trauma ranges from a small capsular tear, without parenchymal laceration, to massive parenchymal injury with major hepatic vein/retrohepatic vena cava lesions. In 1994, the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma (AAST) revised the Hepatic Injury Scale to have a range from grade I to VI. Minor injuries (grade I or II) are the most frequent liver injuries (80% to 90% of all cases); severe injuries are grade III-V lesions; grade VI lesions are frequently incompatible with survival. In the medical literature, the majority of patients who have undergone NOM have low-grade liver injuries. The safety of NOM in high-grade liver lesions, AAST grade IV and V, remains a subject of debate as a high incidence of liver and collateral extra-abdominal complications are still described. To assess the effects of non-operative management compared to operative management in high-grade (grade III-V) blunt hepatic injury. The search for studies was run on 14 April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), PubMed, ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registries, conference proceedings, and we screened reference lists. All randomised trials that compare non-operative management versus operative management in high-grade blunt hepatic injury. Two authors independently applied the selection criteria to relevant study reports. We used standard methodological procedures as defined by the Cochrane Collaboration. We were unable to find any randomised controlled trials of non-operative management versus operative management in high-grade blunt hepatic injury. In order to further explore the preliminary findings provided by animal models and observational clinical studies that suggests there may be a beneficial effect of non-operative management versus operative management in high-grade blunt hepatic injury, large, high quality randomised trials are needed.

Reduced error signalling in medication-naive children with ADHD: associations with behavioural variability and post-error adaptations

PubMed Central

Plessen, Kerstin J.; Allen, Elena A.; Eichele, Heike; van Wageningen, Heidi; Høvik, Marie Farstad; Sørensen, Lin; Worren, Marius Kalsås; Hugdahl, Kenneth; Eichele, Tom

2016-01-01

Background We examined the blood-oxygen level–dependent (BOLD) activation in brain regions that signal errors and their association with intraindividual behavioural variability and adaptation to errors in children with attention-deficit/hyperactivity disorder (ADHD). Methods We acquired functional MRI data during a Flanker task in medication-naive children with ADHD and healthy controls aged 8–12 years and analyzed the data using independent component analysis. For components corresponding to performance monitoring networks, we compared activations across groups and conditions and correlated them with reaction times (RT). Additionally, we analyzed post-error adaptations in behaviour and motor component activations. Results We included 25 children with ADHD and 29 controls in our analysis. Children with ADHD displayed reduced activation to errors in cingulo-opercular regions and higher RT variability, but no differences of interference control. Larger BOLD amplitude to error trials significantly predicted reduced RT variability across all participants. Neither group showed evidence of post-error response slowing; however, post-error adaptation in motor networks was significantly reduced in children with ADHD. This adaptation was inversely related to activation of the right-lateralized ventral attention network (VAN) on error trials and to task-driven connectivity between the cingulo-opercular system and the VAN. Limitations Our study was limited by the modest sample size and imperfect matching across groups. Conclusion Our findings show a deficit in cingulo-opercular activation in children with ADHD that could relate to reduced signalling for errors. Moreover, the reduced orienting of the VAN signal may mediate deficient post-error motor adaptions. Pinpointing general performance monitoring problems to specific brain regions and operations in error processing may help to guide the targets of future treatments for ADHD. PMID:26441332

Importance of associative learning processes for one-trial behavioral sensitization of preweanling rats.

PubMed

McDougall, Sanders A; Pothier, Alexandria G; Der-Ghazarian, Taleen; Herbert, Matthew S; Kozanian, Olga O; Castellanos, Kevin A; Flores, Ana T

2011-10-01

During adulthood, associative learning is necessary for the expression of one-trial behavioral sensitization; however, it is uncertain whether the same associative processes are operative during the preweanling period. Two strategies were used to assess the importance of associative learning for one-trial behavioral sensitization of preweanling rats. In the initial experiments, we varied both the sequence and time interval between presentation of the conditioned stimulus (CS, novel environment) and unconditioned stimulus (US, cocaine). In the final experiment, we determined whether electroconvulsive shock-induced retrograde amnesia would disrupt one-trial behavioral sensitization. Results showed that robust-sensitized responding was apparent regardless of the sequence in which cocaine and the novel environment (the presumptive CS) were presented. Varying the time between CS and US presentation (0, 3, or 6 h) was also without effect. Results from experiment 3 showed that single or multiple electroconvulsive shock treatments did not alter the expression of the sensitized response. Therefore, these data indicated that one-trial behavioral sensitization of preweanling rats was exclusively mediated by nonassociative mechanisms and that associative processes did not modulate sensitized responding. These findings are in contrast to what is observed during adulthood, as adult rats exhibit one-trial behavioral sensitization only when associative processes are operative.

Challenges in conducting a community-based influenza vaccine trial in a rural community in northern India.

PubMed

Kumar, Rakesh; Amarchand, Ritvik; Narayan, Venkatesh Vinayak; Saha, Siddhartha; Lafond, Kathryn E; Kapoor, Suresh K; Dar, Lalit; Jain, Seema; Krishnan, Anand

2018-04-04

Evidence on influenza vaccine effectiveness from low and middle countries (LMICs) is limited due to limited institutional capacities; lack of adequate resources; and lack of interest by ministries of health for influenza vaccine introduction. There are concerns that the highest ethical standards will be compromised during trials in LMICs leading to mistrust of clinical trials. These factors pose regulatory and operational challenges to researchers in these countries. We conducted a community-based vaccine trial to assess the efficacy of live attenuated influenza vaccine and inactivated influenza vaccine in rural north India. Key regulatory challenges included obtaining regulatory approvals, reporting of adverse events, and compensating subjects for trial-related injuries; all of which were required to be completed in a timely fashion. Key operational challenges included obtaining audio-visual consent; maintaining a low attrition rate; and administering vaccines during a narrow time period before the influenza season, and under extreme heat. We overcame these challenges through advanced planning, and sustaining community engagement. We adapted the trial procedures to cope with field conditions by conducting mock vaccine camps; and planned for early morning vaccination to mitigate threats to the cold chain. These lessons may help investigators to confront similar challenges in other LMICs.

Clinical Trials | Division of Cancer Prevention

Cancer.gov

Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |

Protocol for the PREHAB study—Pre-operative Rehabilitation for reduction of Hospitalization After coronary Bypass and valvular surgery: a randomised controlled trial

PubMed Central

Stammers, Andrew N; Kehler, D Scott; Afilalo, Jonathan; Avery, Lorraine J; Bagshaw, Sean M; Grocott, Hilary P; Légaré, Jean-Francois; Logsetty, Sarvesh; Metge, Colleen; Nguyen, Thang; Rockwood, Kenneth; Sareen, Jitender; Sawatzky, Jo-Ann; Tangri, Navdeep; Giacomantonio, Nicholas; Hassan, Ansar; Duhamel, Todd A; Arora, Rakesh C

2015-01-01

Introduction Frailty is a geriatric syndrome characterised by reductions in muscle mass, strength, endurance and activity level. The frailty syndrome, prevalent in 25–50% of patients undergoing cardiac surgery, is associated with increased rates of mortality and major morbidity as well as function decline postoperatively. This trial will compare a preoperative, interdisciplinary exercise and health promotion intervention to current standard of care (StanC) for elective coronary artery bypass and valvular surgery patients for the purpose of determining if the intervention improves 3-month and 12-month clinical outcomes among a population of frail patients waiting for elective cardiac surgery. Methods and analysis This is a multicentre, randomised, open end point, controlled trial using assessor blinding and intent-to-treat analysis. Two-hundred and forty-four elective cardiac surgical patients will be recruited and randomised to receive either StanC or StanC plus an 8-week exercise and education intervention at a certified medical fitness facility. Patients will attend two weekly sessions and aerobic exercise will be prescribed at 40–60% of heart rate reserve. Data collection will occur at baseline, 1–2 weeks preoperatively, and at 3 and 12 months postoperatively. The primary outcome of the trial will be the proportion of patients requiring a hospital length of stay greater than 7 days. Potential impact of study The healthcare team is faced with an increasingly complex older adult patient population. As such, this trial aims to provide novel evidence supporting a health intervention to ensure that frail, older adult patients thrive after undergoing cardiac surgery. Ethics and dissemination Trial results will be published in peer-reviewed journals, and presented at national and international scientific meetings. The University of Manitoba Health Research Ethics Board has approved the study protocol V.1.3, dated 11 August 2014 (H2014:208). Trial registration number The trial has been registered on ClinicalTrials.gov, a registry and results database of privately and publicly funded clinical studies (NCT02219815). PMID:25753362

Sensitivity study of Space Station Freedom operations cost and selected user resources

NASA Technical Reports Server (NTRS)

Accola, Anne; Fincannon, H. J.; Williams, Gregory J.; Meier, R. Timothy

1990-01-01

The results of sensitivity studies performed to estimate probable ranges for four key Space Station parameters using the Space Station Freedom's Model for Estimating Space Station Operations Cost (MESSOC) are discussed. The variables examined are grouped into five main categories: logistics, crew, design, space transportation system, and training. The modification of these variables implies programmatic decisions in areas such as orbital replacement unit (ORU) design, investment in repair capabilities, and crew operations policies. The model utilizes a wide range of algorithms and an extensive trial logistics data base to represent Space Station operations. The trial logistics data base consists largely of a collection of the ORUs that comprise the mature station, and their characteristics based on current engineering understanding of the Space Station. A nondimensional approach is used to examine the relative importance of variables on parameters.

AplusB: A Web Application for Investigating A + B Designs for Phase I Cancer Clinical Trials.

PubMed

Wheeler, Graham M; Sweeting, Michael J; Mander, Adrian P

2016-01-01

In phase I cancer clinical trials, the maximum tolerated dose of a new drug is often found by a dose-escalation method known as the A + B design. We have developed an interactive web application, AplusB, which computes and returns exact operating characteristics of A + B trial designs. The application has a graphical user interface (GUI), requires no programming knowledge and is free to access and use on any device that can open an internet browser. A customised report is available for download for each design that contains tabulated operating characteristics and informative plots, which can then be compared with other dose-escalation methods. We present a step-by-step guide on how to use this application and provide several illustrative examples of its capabilities.

Operative versus nonoperative treatment for acute Achilles tendon rupture: a meta-analysis based on current evidence.

PubMed

Jiang, Nan; Wang, Bowei; Chen, Anfu; Dong, Fu; Yu, Bin

2012-04-01

The aim of this study was to evaluate, in a meta-analysis, the clinical effectiveness of operative treatment for acute Achilles tendon rupture (AATR) compared with nonoperative treatment. We systematically searched six electronic databases (Medline, Embase, Clinical Ovid, BIOSIS and Cochrane registry of controlled clinical trials) to identify randomised controlled trials (RCTs) in which operative treatment was compared with nonoperative treatment for AATR from 1980 to 2011. Trial quality was assessed using the modified Jadad scale. The data was using fixed-effects and random-effects models with mean differences and risk ratios for continuous and dichotomous variables, respectively. Ten RCTs with a total of 894 patients were screened. The results showed that operative was superior to nonoperative treatment regarding lower risk of re-rupture (P = 0.002) and shorter time for sick leave (P = 0.009) but inferior to nonoperative treatment regarding complication risks (P = 0.004). No significant difference was identified between the two methods regarding the number of patients who successfully returned to pre-injury sports (P = 0.30). Subgroup analyses revealed significant differences in relation to scar adhesion (P < 0.00001), superficial infection (P = 0.05), and sensibility disturbance (P = 0.0003). However, no significant differences were found between the two interventions in relation to deep infection (P = 0.22), deep vein thrombosis (DVT) (P = 0.14), and extreme Achilles tendon lengthening (P = 0.31). Little consensus was obtained in the functional recovery from current trials as a result of an inconsistent assessment system. Compared with conservative treatment, operative treatment can effectively reduce the risk of re-rupture but increase the probability of complications. The increased complication risk may be associated with open repair surgery. However, no sufficient evidence is available from current studies to support the belief that operation may lead to better functional recovery.

Randomized Controlled Trial of Supplemental Augmentative and Alternative Communication versus Voice Rest Alone after Phonomicrosurgery

PubMed Central

Rousseau, Bernard; Gutmann, Michelle L.; Mau, I-fan Theodore; Francis, David O.; Johnson, Jeffrey P.; Novaleski, Carolyn K.; Vinson, Kimberly N.; Garrett, C. Gaelyn

2015-01-01

Objective This randomized trial investigated voice rest and supplemental text-to-speech communication versus voice rest alone on visual analog scale measures of communication effectiveness and magnitude of voice use. Study Design Randomized clinical trial. Setting Multicenter outpatient voice clinics. Subjects Thirty-seven patients undergoing phonomicrosurgery. Methods Patients undergoing phonomicrosurgery were randomized to voice rest and supplemental text-to-speech communication or voice rest alone. The primary outcome measure was the impact of voice rest on ability to communicate effectively over a seven-day period. Pre- and post-operative magnitude of voice use was also measured as an observational outcome. Results Patients randomized to voice rest and supplemental text-to-speech communication reported higher median communication effectiveness on each post-operative day compared to those randomized to voice rest alone, with significantly higher median communication effectiveness on post-operative day 3 (p = 0.03) and 5 (p = 0.01). Magnitude of voice use did not differ on any pre-operative (p > 0.05) or post-operative day (p > 0.05), nor did patients significantly decrease voice use as the surgery date approached (p > 0.05). However, there was a significant reduction in median voice use pre- to post-operatively across patients (p < 0.001) with median voice use ranging from 0–3 throughout the post-operative week. Conclusion Supplemental text-to-speech communication increased patient perceived communication effectiveness on post-operative days 3 and 5 over voice rest alone. With the prevalence of smartphones and the widespread use of text messaging, supplemental text-to-speech communication may provide an accessible and cost-effective communication option for patients on vocal restrictions. PMID:25605690

Laparoscopic surgical box model training for surgical trainees with limited prior laparoscopic experience.

PubMed

Gurusamy, Kurinchi Selvan; Nagendran, Myura; Toon, Clare D; Davidson, Brian R

2014-03-01

Surgical training has traditionally been one of apprenticeship, where the surgical trainee learns to perform surgery under the supervision of a trained surgeon. This is time consuming, costly, and of variable effectiveness. Training using a box model physical simulator is an option to supplement standard training. However, the value of this modality on trainees with limited prior laparoscopic experience is unknown. To compare the benefits and harms of box model training for surgical trainees with limited prior laparoscopic experience versus standard surgical training or supplementary animal model training. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to May 2013. We planned to include all randomised clinical trials comparing box model trainers versus other forms of training including standard laparoscopic training and supplementary animal model training in surgical trainees with limited prior laparoscopic experience. We also planned to include trials comparing different methods of box model training. Two authors independently identified trials and collected data. We analysed the data with both the fixed-effect and the random-effects models using Review Manager 5. For each outcome, we calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI) based on intention-to-treat analysis whenever possible. We identified eight trials that met the inclusion criteria. One trial including 17 surgical trainees did not contribute to the meta-analysis. We included seven trials (249 surgical trainees belonging to various postgraduate years ranging from year one to four) in which the participants were randomised to supplementary box model training (122 trainees) versus standard training (127 trainees). Only one trial (50 trainees) was at low risk of bias. The box trainers used in all the seven trials were video trainers. Six trials were conducted in USA and one trial in Canada. The surgeries in which the final assessments were made included laparoscopic total extraperitoneal hernia repairs, laparoscopic cholecystectomy, laparoscopic tubal ligation, laparoscopic partial salpingectomy, and laparoscopic bilateral mid-segment salpingectomy. The final assessments were made on a single operative procedure.There were no deaths in three trials (0/82 (0%) supplementary box model training versus 0/86 (0%) standard training; RR not estimable; very low quality evidence). The other trials did not report mortality. The estimated effect on serious adverse events was compatible with benefit and harm (three trials; 168 patients; 0/82 (0%) supplementary box model training versus 1/86 (1.1%) standard training; RR 0.36; 95% CI 0.02 to 8.43; very low quality evidence). None of the trials reported patient quality of life. The operating time was significantly shorter in the supplementary box model training group versus the standard training group (1 trial; 50 patients; MD -6.50 minutes; 95% CI -10.85 to -2.15). The proportion of patients who were discharged as day-surgery was significantly higher in the supplementary box model training group versus the standard training group (1 trial; 50 patients; 24/24 (100%) supplementary box model training versus 15/26 (57.7%) standard training; RR 1.71; 95% CI 1.23 to 2.37). None of the trials reported trainee satisfaction. The operating performance was significantly better in the supplementary box model training group versus the standard training group (seven trials; 249 trainees; SMD 0.84; 95% CI 0.57 to 1.10).None of the trials compared box model training versus animal model training or versus different methods of box model training. There is insufficient evidence to determine whether laparoscopic box model training reduces mortality or morbidity. There is very low quality evidence that it improves technical skills compared with standard surgical training in trainees with limited previous laparoscopic experience. It may also decrease operating time and increase the proportion of patients who were discharged as day-surgery in the first total extraperitoneal hernia repair after box model training. However, the duration of the benefit of box model training is unknown. Further well-designed trials of low risk of bias and random errors are necessary. Such trials should assess the long-term impact of box model training on clinical outcomes and compare box training with other forms of training.

Transient Receptor Potential Canonical (TRPC)/Orai1-dependent Store-operated Ca2+ Channels: NEW TARGETS OF ALDOSTERONE IN CARDIOMYOCYTES.

PubMed

Sabourin, Jessica; Bartoli, Fiona; Antigny, Fabrice; Gomez, Ana Maria; Benitah, Jean-Pierre

2016-06-17

Store-operated Ca(2+) entry (SOCE) has emerged as an important mechanism in cardiac pathology. However, the signals that up-regulate SOCE in the heart remain unexplored. Clinical trials have emphasized the beneficial role of mineralocorticoid receptor (MR) signaling blockade in heart failure and associated arrhythmias. Accumulated evidence suggests that the mineralocorticoid hormone aldosterone, through activation of its receptor, MR, might be a key regulator of Ca(2+) influx in cardiomyocytes. We thus assessed whether and how SOCE involving transient receptor potential canonical (TRPC) and Orai1 channels are regulated by aldosterone/MR in neonatal rat ventricular cardiomyocytes. Molecular screening using qRT-PCR and Western blotting demonstrated that aldosterone treatment for 24 h specifically increased the mRNA and/or protein levels of Orai1, TRPC1, -C4, -C5, and stromal interaction molecule 1 through MR activation. These effects were correlated with a specific enhancement of SOCE activities sensitive to store-operated channel inhibitors (SKF-96365 and BTP2) and to a potent Orai1 blocker (S66) and were prevented by TRPC1, -C4, and Orai1 dominant negative mutants or TRPC5 siRNA. A mechanistic approach showed that up-regulation of serum- and glucocorticoid-regulated kinase 1 mRNA expression by aldosterone is involved in enhanced SOCE. Functionally, 24-h aldosterone-enhanced SOCE is associated with increased diastolic [Ca(2+)]i, which is blunted by store-operated channel inhibitors. Our study provides the first evidence that aldosterone promotes TRPC1-, -C4-, -C5-, and Orai1-mediated SOCE in cardiomyocytes through an MR and serum- and glucocorticoid-regulated kinase 1 pathway. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Transient Receptor Potential Canonical (TRPC)/Orai1-dependent Store-operated Ca2+ Channels

PubMed Central

Sabourin, Jessica; Bartoli, Fiona; Antigny, Fabrice; Gomez, Ana Maria; Benitah, Jean-Pierre

2016-01-01

Store-operated Ca2+ entry (SOCE) has emerged as an important mechanism in cardiac pathology. However, the signals that up-regulate SOCE in the heart remain unexplored. Clinical trials have emphasized the beneficial role of mineralocorticoid receptor (MR) signaling blockade in heart failure and associated arrhythmias. Accumulated evidence suggests that the mineralocorticoid hormone aldosterone, through activation of its receptor, MR, might be a key regulator of Ca2+ influx in cardiomyocytes. We thus assessed whether and how SOCE involving transient receptor potential canonical (TRPC) and Orai1 channels are regulated by aldosterone/MR in neonatal rat ventricular cardiomyocytes. Molecular screening using qRT-PCR and Western blotting demonstrated that aldosterone treatment for 24 h specifically increased the mRNA and/or protein levels of Orai1, TRPC1, -C4, -C5, and stromal interaction molecule 1 through MR activation. These effects were correlated with a specific enhancement of SOCE activities sensitive to store-operated channel inhibitors (SKF-96365 and BTP2) and to a potent Orai1 blocker (S66) and were prevented by TRPC1, -C4, and Orai1 dominant negative mutants or TRPC5 siRNA. A mechanistic approach showed that up-regulation of serum- and glucocorticoid-regulated kinase 1 mRNA expression by aldosterone is involved in enhanced SOCE. Functionally, 24-h aldosterone-enhanced SOCE is associated with increased diastolic [Ca2+]i, which is blunted by store-operated channel inhibitors. Our study provides the first evidence that aldosterone promotes TRPC1-, -C4-, -C5-, and Orai1-mediated SOCE in cardiomyocytes through an MR and serum- and glucocorticoid-regulated kinase 1 pathway. PMID:27129253

Effects of preoperative aspirin on perioperative platelet activation and dysfunction in patients undergoing off-pump coronary artery bypass graft surgery: A prospective randomized study.

PubMed

Lee, Jiwon; Jung, Chul-Woo; Jeon, Yunseok; Kim, Tae Kyong; Cho, Youn Joung; Koo, Chang-Hoon; Choi, Yoon Hyeong; Kim, Ki-Bong; Hwang, Ho Young; Kim, Hang-Rae; Park, Ji-Young

2017-01-01

The benefit of aspirin use after coronary artery bypass graft surgery has been well proven. However, the effect of preoperative aspirin use in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB) has not been evaluated sufficiently. To evaluate platelet function changes during OPCAB due to preoperative aspirin use, we conducted a randomized controlled trial using flow cytometry and the Multiplate® analyzer. Forty-eight patients scheduled for elective OPCAB were randomized to the aspirin continuation (100 mg/day until operative day) and discontinuation (4 days before the operative day) groups. Platelet function was measured using the platelet activation markers CD62P, CD63, and PAC-1 by flow cytometry, and platelet aggregation was measured using the Multiplate® analyzer, after the induction of anesthesia (baseline), at the end of the operation, and 24 and 48 h postoperatively. Findings of conventional coagulation assays, thromboelastography by ROTEM® assays, and postoperative bleeding-related clinical outcomes were compared between groups. No significant change in CD62P, CD63, or PAC-1 was observed at the end of the operation or 24 or 48 h postoperatively compared with baseline in either group. The area under the curve for arachidonic acid-stimulated platelet aggregation, measured by the Multiplate® analyzer, was significantly smaller in the aspirin continuation group (P < 0.01). However, chest tube drainage and intraoperative and postoperative transfusion requirements did not differ between groups. Our study showed that preoperative use of aspirin for OPCAB did not affect perioperative platelet activation, but it impaired platelet aggregation, which did not affect postoperative bleeding, by arachidonic acid.

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

PubMed

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

2016-10-04

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

Probabilistic Inference in General Graphical Models through Sampling in Stochastic Networks of Spiking Neurons

PubMed Central

Pecevski, Dejan; Buesing, Lars; Maass, Wolfgang

2011-01-01

An important open problem of computational neuroscience is the generic organization of computations in networks of neurons in the brain. We show here through rigorous theoretical analysis that inherent stochastic features of spiking neurons, in combination with simple nonlinear computational operations in specific network motifs and dendritic arbors, enable networks of spiking neurons to carry out probabilistic inference through sampling in general graphical models. In particular, it enables them to carry out probabilistic inference in Bayesian networks with converging arrows (“explaining away”) and with undirected loops, that occur in many real-world tasks. Ubiquitous stochastic features of networks of spiking neurons, such as trial-to-trial variability and spontaneous activity, are necessary ingredients of the underlying computational organization. We demonstrate through computer simulations that this approach can be scaled up to neural emulations of probabilistic inference in fairly large graphical models, yielding some of the most complex computations that have been carried out so far in networks of spiking neurons. PMID:22219717

Benefits and problems of health-care robots in aged care settings: A comparison trial.

PubMed

Broadbent, Elizabeth; Kerse, Ngaire; Peri, Kathryn; Robinson, Hayley; Jayawardena, Chandimal; Kuo, Tony; Datta, Chandan; Stafford, Rebecca; Butler, Haley; Jawalkar, Pratyusha; Amor, Maddy; Robins, Ben; MacDonald, Bruce

2016-03-01

This study investigated whether multiple health-care robots could have any benefits or cause any problems in an aged care facility. Fifty-three residents and 53 staff participated in a non-randomised controlled trial over 12 weeks. Six robots provided entertainment, communication and health-monitoring functions in staff rooms and activity lounges. These settings were compared to control settings without robots. There were no significant differences between groups in resident or staff outcomes, except a significant increase in job satisfaction in the control group only. The intervention group perceived the robots had more agency and experience than the control group did. Perceived agency of the robots decreased over time in both groups. Overall, we received very mixed responses with positive, neutral and negative comments. The robots had no major benefits or problems. Future research could give robots stronger operational roles, use more specific outcome measures, and perform cost-benefit analyses. © 2015 AJA Inc.

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain.

PubMed

Younger, Jarred; Parkitny, Luke; McLain, David

2014-04-01

Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.

Results and experiences from the NATO Common Shield DAT#7 experiment for the Defence Against Terrorism program

NASA Astrophysics Data System (ADS)

Peichl, Markus; Dill, Stephan; Jirousek, Matthias; Süß, Helmut

2009-05-01

Passive microwave imaging allows a daytime independent observation and examination of objects and persons without artificial exposure under nearly all weather conditions. The penetration capability of microwaves allows the detection of hidden objects like weapons and explosive devices under the clothing. In August/September 2008 a comprehensive military experiment was conducted by the German armed forces at the naval base Eckernfoerde, Germany. One activity in the Eckernfoerde trial was the simulation of a military entrance portal by a tent including various imaging and a chemical sensor suite. Besides commercial optical and infrared cameras various passive millimeter-wave imagers have been used from different German research institutions. The DLR Microwaves and Radar Institute, Department for Reconnaissance and Security (HR-AS), provided an imaging radiometer scanner operating at W band. A multitude of situations have been simulated and many persons carrying hidden objects under their clothing have been scanned. Some exemplary results from the trial are shown and discussed in the paper.

Invasion of the Zebra Mussels: A Mock Trial Activity

ERIC Educational Resources Information Center

Beck, Judy A.; Czerniak, Charlene M.

2005-01-01

In this activity, students learn about the important topic of invasive species, specifically Zebra Mussels. Students role-play different characters in a real-life situation: the trial of the Zebra Mussel for unlawful disruption of the Great Lakes ecosystem. Students will also learn about jurisprudential inquiry by examining the trial process. This…

A functional magnetic resonance imaging investigation of short-term source and item memory for negative pictures.

PubMed

Mitchell, Karen J; Mather, Mara; Johnson, Marcia K; Raye, Carol L; Greene, Erich J

2006-10-02

We investigated the hypothesis that arousal recruits attention to item information, thereby disrupting working memory processes that help bind items to context. Using functional magnetic resonance imaging, we compared brain activity when participants remembered negative or neutral picture-location conjunctions (source memory) versus pictures only. Behaviorally, negative trials showed disruption of short-term source, but not picture, memory; long-term picture recognition memory was better for negative than for neutral pictures. Activity in areas involved in working memory and feature integration (precentral gyrus and its intersect with superior temporal gyrus) was attenuated on negative compared with neutral source trials relative to picture-only trials. Visual processing areas (middle occipital and lingual gyri) showed greater activity for negative than for neutral trials, especially on picture-only trials.

Positive Emotion Facilitates Cognitive Flexibility: An fMRI Study

PubMed Central

Wang, Yanmei; Chen, Jie; Yue, Zhenzhu

2017-01-01

Cognitive flexibility is the ability to switch rapidly between multiple goals. By using a task-switching paradigm, the present study investigated how positive emotion affected cognitive flexibility and the underlying neural mechanisms. After viewing pictures of different emotional valence (positive, negative, or neutral), participants discriminated whether a target digit in a specific color was odd or even. After a series of trials, the color of target stimuli was changed, i.e., the switch condition. Switch costs were measured by the increase of reaction times (RTs) in the switch trials compared to those in the repeat trials. Behavior results indicated that switch costs significantly decreased in the positive emotional condition, and increased in the negative emotional condition, compared with those in the neutral condition. Imaging data revealed enhanced activation in the dorsal anterior cingulate cortex (dACC) in switch trials than those in repeat trials. Moreover, the interaction between emotion (positive, negative, neutral) and trial type (repeat vs. switch) was significant. For switch trials, the activation of dACC decreased significantly in the positive condition, while increased significantly in the negative condition compared to neutral condition. By contrast, for repeat trials, no significant difference was observed for the activation of dACC among three emotional conditions. Our results showed that positive emotions could increase the cognitive flexibility and reduce the conflict by decreasing the activation of dACC. PMID:29163255

47 CFR 5.602 - Market trials.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EXPERIMENTAL RADIO SERVICE Product Development and..., experimental radio licenses granted for the purpose of market trials pursuant to § 5.3(k) are subject to the... authorized under this rule section, including those devices that are designed to operate under parts 15, 18...

47 CFR 5.602 - Market trials.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EXPERIMENTAL RADIO SERVICE Product Development and..., experimental radio licenses granted for the purpose of market trials pursuant to § 5.3(k) are subject to the... authorized under this rule section, including those devices that are designed to operate under parts 15, 18...

Women's Health and Complementary Approaches

MedlinePlus

... Information Center Ongoing Medical Studies Find Active Medical Research Studies on Cranberry (ClinicalTrials.gov) Find Active Medical Research Studies on Menopause (ClinicalTrials.gov) Safety Information Dream Body ...

Evaluating the Process of Generating a Clinical Trial Protocol

PubMed Central

Franciosi, Lui G.; Butterfield, Noam N.; MacLeod, Bernard A.

2002-01-01

The research protocol is the principal document in the conduct of a clinical trial. Its generation requires knowledge about the research problem, the potential experimental confounders, and the relevant Good Clinical Practices for conducting the trial. However, such information is not always available to authors during the writing process. A checklist of over 80 items has been developed to better understand the considerations made by authors in generating a protocol. It is based on the most cited requirements for designing and implementing the randomised controlled trial. Items are categorised according to the trial's research question, experimental design, statistics, ethics, and standard operating procedures. This quality assessment tool evaluates the extent that a generated protocol deviates from the best-planned clinical trial.

Inflammatory bowel disease after 1932.

PubMed

Janowitz, H D

2000-05-01

The clinical diseases of ulcerative colitis (UC) and Crohn's disease (CD) were defined by 1932-1933. After that, the major conceptual developments were the recognition that regional enteritis could clearly involve the colon, and that cancer and toxic megacolon could occur in both CD and UC. In the last half of the 20th century the main thrust of gastroenterology at The Mount Sinai Hospital has been in inflammatory bowel disease (IBD), with contributions to extra-intestinal manifestations, measurement of clinical activity in CD, the natural history of the placebo arm of controlled trials, complications and therapy with corticosteroids, 5-ASA, 6-mercaptopurine, immunomodulators and cyclosporine. Actuarial life tables were introduced for postoperative recurrence and re-operation rates, as well as for quality of life analysis. Two forms of CD were defined, perforating and non-perforating, and the role of the fecal stream was explored in light of the higher risk of recurrence after operations with anastomosis as compared with ileocolostomy.

New aspects in Peyronie's disease--a mini-review.

PubMed

Schroeder-Printzen, I; Hauck, E W; Weidner, W

1999-01-01

There have been several advances in elucidation of the pathogenesis of Peyronie's disease. Transforming growth factor beta 1 seems to play a major role in this disease, while the importance of penile trauma is a matter of debate. High-resolution ultrasound sonography is the method of choice in detecting penile plaques, while magnetic resonance imaging is useful in the evaluation of actively inflamed plaques. There are still differences of opinion on the best drug therapy in noncalcified plaques. The results on tamoxifen or interferon therapy vary between useless and useful. Potassium-para-aminobenzoate seems to have a significant effect in decreasing plaque size and deviation angle. The operative strategy for big plaques or complex deviation has changed to the 'small incision' graft, leading to far lower post-operative impotence rates. Iontophoresis seems to be worthy of further trials, while the results of extracorporal shock wave therapy have to be discussed critically.

Comparison of Veteran experiences of low-cost, home-based diet and exercise interventions.

PubMed

Holtz, Bree; Krein, Sarah L; Bentley, Douglas R; Hughes, Maria E; Giardino, Nicholas D; Richardson, Caroline R

2014-01-01

Obesity is a significant health problem among Veterans who receive care from the Department of Veterans Affairs, as it is for so many other Americans. Veterans from Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) experience a myriad of chronic conditions, which can make it difficult to maintain a physically active lifestyle. This pilot study tested the feasibility and user satisfaction with three low-cost, home-based diet and exercise programs, as well as point-of-decision prompts among these Veterans. The three programs target mechanisms that have been shown to improve healthy behavior change, including (1) online mediated social support, (2) objective monitoring of physical activity, and (3) structured high-intensity workouts. This was a randomized crossover trial; each participant used two of the three programs, and all used the point-of-decision prompts. Our qualitative results identified five overall themes related to social support, objective monitoring, structured activity, awareness and understanding, and the point-of-decision prompts. In general, participants were satisfied with and lost weight with each of the interventions. This study demonstrated that these low-cost interventions could be successful with the OIF/OEF Veteran population. A larger and longer study is planned to further investigate the effectiveness of these interventions.

The effect of local anaesthetic wound infiltration on chronic pain after lower limb joint replacement: A protocol for a double-blind randomised controlled trial

PubMed Central

2011-01-01

Background For the majority of patients with osteoarthritis (OA), joint replacement is a successful intervention for relieving chronic joint pain. However, between 10-30% of patients continue to experience chronic pain after joint replacement. Evidence suggests that a risk factor for chronic pain after joint replacement is the severity of acute post-operative pain. The aim of this randomised controlled trial (RCT) is to determine if intra-operative local anaesthethic wound infiltration additional to a standard anaethesia regimen can reduce the severity of joint pain at 12-months after total knee replacement (TKR) and total hip replacement (THR) for OA. Methods 300 TKR patients and 300 THR patients are being recruited into this single-centre double-blind RCT. Participants are recruited before surgery and randomised to either the standard care group or the intervention group. Participants and outcome assessors are blind to treatment allocation throughout the study. The intervention consists of an intra-operative local anaesthetic wound infiltration, consisting of 60 mls of 0.25% bupivacaine with 1 in 200,000 adrenaline. Participants are assessed on the first 5 days post-operative, and then at 3-months, 6-months and 12-months. The primary outcome is the WOMAC Pain Scale, a validated measure of joint pain at 12-months. Secondary outcomes include pain severity during the in-patient stay, post-operative nausea and vomiting, satisfaction with pain relief, length of hospital stay, joint pain and disability, pain sensitivity, complications and cost-effectiveness. A nested qualitative study within the RCT will examine the acceptability and feasibility of the intervention for both patients and healthcare professionals. Discussion Large-scale RCTs assessing the effectiveness of a surgical intervention are uncommon, particulary in orthopaedics. The results from this trial will inform evidence-based recommendations for both short-term and long-term pain management after lower limb joint replacement. If a local anaesthetic wound infiltration is found to be an effective and cost-effective intervention, implementation into clinical practice could improve long-term pain outcomes for patients undergoing lower limb joint replacement. Trial registration Current Controlled Trials ISRCTN96095682 PMID:21352559

Face washing promotion for preventing active trachoma

PubMed Central

Ejere, Henry OD; Alhassan, Mahmoud B; Rabiu, Mansur

2015-01-01

Background Trachoma remains a major cause of avoidable blindness among underprivileged populations in many developing countries. It is estimated that about 146 million people have active trachoma and nearly six million people are blind due to complications associated with repeat infections. Objectives The objective of this review was to assess the effects of face washing promotion for the prevention of active trachoma in endemic communities. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), PubMed (January 1948 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (accessed 10 January 2014), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 26 January 2015. To identify further relevant trials we checked the reference lists of the included trials. Also, we used the Science Citation Index to search for references to publications that cited the trials included in the review. We contacted investigators and experts in the field to identify additional trials. Selection criteria We included randomized controlled trials (RCTs) or quasi-RCTs that compared face washing with no treatment or face washing combined with antibiotics against antibiotics alone. Trial participants were residents of endemic trachoma communities. Data collection and analysis Two review authors independently extracted data and assessed trial quality. We contacted trial authors for additional information when needed. Two trials met our inclusion criteria; but we did not conduct meta-analysis due to methodological heterogeneity. Main results We included two cluster-RCTs, which provided data from 2447 participants. Both trials were conducted in areas endemic to trachoma: Northern Australia and Tanzania. The follow-up period was three months in one trial and 12 months in the other; both trials had about 90% participant follow-up at final visit. Overall the quality of the evidence is uncertain due to the trials not reporting many design methods and the differences in outcomes reported between trials. Face washing combined with topical tetracycline was compared with topical tetracycline alone in three pairs of villages in one trial. The trial found that face washing combined with topical tetracycline reduced ’severe’ active trachoma compared with topical tetracycline alone at 12 months (adjusted odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.97); however, the trial did not find any important difference between the intervention and control villages in reducing other types of active trachoma (adjusted OR 0.81, 95% CI 0.42 to 1.59). Intervention villages had a higher prevalence of clean faces than the control villages among children with severe trachoma (adjusted OR 0.35, 95% CI 0.21 to 0.59) and any trachoma (adjusted OR 0.58, 95% CI 0.47 to 0.72) at 12 months follow-up. The second trial compared eye washing to no treatment or to topical tetracycline alone or to a combination of eye washing and tetracycline drops in children with follicular trachoma. At three months, the trial found no evidence of benefit of eye washing alone or in combination with tetracycline eye drops in reducing follicular trachoma amongst children with follicular trachoma (risk ratio (RR) 1.03, 95% CI 0.96 to 1.11; one trial, 1143 participants). Authors’ conclusions There is evidence from one trial that face washing combined with topical tetracycline may be effective in reducing severe active trachoma and in increasing the prevalence of clean faces at one year follow-up. Current evidence is inconclusive as to the effectiveness of face washing alone or in combination with topical tetracycline in reducing active or severe trachoma. PMID:25697765

Effects of Working Memory Demand on Neural Mechanisms of Motor Response Selection and Control

PubMed Central

Barber, Anita D.; Caffo, Brian S.; Pekar, James J.; Mostofsky, Stewart H.

2013-01-01

Inhibitory control commonly recruits a number of frontal regions: pre-supplementary motor area (pre-SMA), frontal eye fields (FEFs), and right-lateralized posterior inferior frontal gyrus (IFG), dorsal anterior insula (DAI), dorsolateral prefrontal cortex (DLPFC), and inferior frontal junction (IFJ). These regions may directly implement inhibitory motor control or may be more generally involved in executive control functions. Two go/no-go tasks were used to distinguish regions specifically recruited for inhibition from those that additionally show increased activity with working memory demand. The pre-SMA and IFG were recruited for inhibition in both tasks and did not have greater activation for working memory demand on no-go trials, consistent with a role in inhibitory control. Activation in pre-SMA also responded to response selection demand and was increased with working memory on go trials specifically. The bilateral FEF and right DAI were commonly active for no-go trials. The FEF was also recruited to a greater degree with working memory demand on go trials and may bias top–down information when stimulus–response mappings change. The DAI, additionally responded to increased working memory demand on both go and no-go trials and may be involved in accessing sustained task information, alerting, or autonomic changes when cognitive demands increase. DLPFC activation was consistent with a role in working memory retrieval on both go and no-go trials. The inferior frontal junction, on the other hand, had greater activation with working memory specifically for no-go trials and may detect salient stimuli when the task requires frequent updating of working memory representations. PMID:23530923

The application of active side arm controllers in helicopters

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

Ultrasonic dissection versus electrocautery in mastectomy for breast cancer - a meta-analysis.

PubMed

Currie, A; Chong, K; Davies, G L; Cummins, R S

2012-10-01

Electrocautery has advanced the practice of mastectomy but significant morbidity, such as seroma and blood loss, remains a concern. This has led to newer forms of dissection being introduced including the ultrasonic dissection devices, which are thought to reduce tissue damage. The aim of this systematic review was to compare the outcomes after mastectomy using novel ultrasonic dissection or standard electrocautery in published trials. Medline, Embase, trial registries, conference proceedings and reference lists were searched for comparative trials of ultrasonic dissection versus electrocautery for mastectomy. The primary outcomes were total postoperative drainage, seroma development and intra-operative blood loss. Secondary outcomes were operative time and wound complications. Odds ratios were calculated for categorical outcomes and standardised mean differences for continuous outcomes. Six trials were included in the analysis of 287 mastectomies. There was no effect in total postoperative drainage (pooled analysis weight mean difference: -0.21 (95% CI: -0.70-0.29); p = 0.41) or seroma development (pooled analysis odds ratio: 0.77 (95% CIs 0.43-1.37); p = 0.37). Intra-operative blood was slightly less for ultrasonic dissection compared to standard electrocautery (pooled analysis weight mean difference: -1.04 (95% CI: -2.00 to -0.08); p = 0.03). Ultrasonic dissection and standard electrocautery had similar outcomes with regard to operative time and wound complications. Ultrasonic dissection and standard electrocautery appear to deliver similar results in the mastectomy setting. Further cost-effectiveness analysis may guide surgeon selection in the use of new technologies for mastectomy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of virtual reality training on laparoscopic surgery: randomised controlled trial

PubMed Central

Soerensen, Jette L; Grantcharov, Teodor P; Dalsgaard, Torur; Schouenborg, Lars; Ottosen, Christian; Schroeder, Torben V; Ottesen, Bent S

2009-01-01

Objective To assess the effect of virtual reality training on an actual laparoscopic operation. Design Prospective randomised controlled and blinded trial. Setting Seven gynaecological departments in the Zeeland region of Denmark. Participants 24 first and second year registrars specialising in gynaecology and obstetrics. Interventions Proficiency based virtual reality simulator training in laparoscopic salpingectomy and standard clinical education (controls). Main outcome measure The main outcome measure was technical performance assessed by two independent observers blinded to trainee and training status using a previously validated general and task specific rating scale. The secondary outcome measure was operation time in minutes. Results The simulator trained group (n=11) reached a median total score of 33 points (interquartile range 32-36 points), equivalent to the experience gained after 20-50 laparoscopic procedures, whereas the control group (n=10) reached a median total score of 23 (22-27) points, equivalent to the experience gained from fewer than five procedures (P<0.001). The median total operation time in the simulator trained group was 12 minutes (interquartile range 10-14 minutes) and in the control group was 24 (20-29) minutes (P<0.001). The observers’ inter-rater agreement was 0.79. Conclusion Skills in laparoscopic surgery can be increased in a clinically relevant manner using proficiency based virtual reality simulator training. The performance level of novices was increased to that of intermediately experienced laparoscopists and operation time was halved. Simulator training should be considered before trainees carry out laparoscopic procedures. Trial registration ClinicalTrials.gov NCT00311792. PMID:19443914

Advanced geophysical underground coal gasification monitoring

DOE PAGES

Mellors, Robert; Yang, X.; White, J. A.; ...

2014-07-01

Underground Coal Gasification (UCG) produces less surface impact, atmospheric pollutants and greenhouse gas than traditional surface mining and combustion. Therefore, it may be useful in mitigating global change caused by anthropogenic activities. Careful monitoring of the UCG process is essential in minimizing environmental impact. Here we first summarize monitoring methods that have been used in previous UCG field trials. We then discuss in more detail a number of promising advanced geophysical techniques. These methods – seismic, electromagnetic, and remote sensing techniques – may provide improved and cost-effective ways to image both the subsurface cavity growth and surface subsidence effects. Activemore » and passive seismic data have the promise to monitor the burn front, cavity growth, and observe cavity collapse events. Electrical resistance tomography (ERT) produces near real time tomographic images autonomously, monitors the burn front and images the cavity using low-cost sensors, typically running within boreholes. Interferometric synthetic aperture radar (InSAR) is a remote sensing technique that has the capability to monitor surface subsidence over the wide area of a commercial-scale UCG operation at a low cost. It may be possible to infer cavity geometry from InSAR (or other surface topography) data using geomechanical modeling. The expected signals from these monitoring methods are described along with interpretive modeling for typical UCG cavities. They are illustrated using field results from UCG trials and other relevant subsurface operations.« less

Evaluation of the injection pain with the use of DentalVibe injection system during supraperiosteal anaesthesia in children: a randomised clinical trial.

PubMed

Şermet Elbay, Ülkü; Elbay, Mesut; Yıldırım, Sİnem; Kaya, Emİne; Kaya, Can; Uğurluel, Ceren; Baydemİr, Canan

2016-09-01

The purpose of this study was to compare the use of a traditional syringe (TS) and the DentalVibe (DV) Injection Comfort System on the pain of needle insertion and injection of supraperiosteal (SP) anaesthesia into the mandibles and maxillas of children aged 6-12 years. The study was a randomised, controlled, crossover clinical trial, comprising 60 children requiring an operative procedure with SP anaesthesia on both their mandibular and maxillary molars, bilaterally. One of the molars was treated with a TS, and the contralateral tooth was treated with the DV for both arches. On each visit, subjective and objective pain was evaluated using the Wong-Baker FACES Pain Rating Scale and the Face, Leg, Activity, Cry, Consolability Scale. Patients were asked which technique they preferred. The data were analysed using Wilcoxon signed-rank test, Spearman's correlation test, and Mann-Whitney U-test. No statistically significant differences were noted between TS and DV for pain during injection and needle insertion for supraperiosteal anaesthesia in either the maxillary and mandibular operative procedures. Children experienced similar pain during SP anaesthesia administered with a TS and the DV, regardless of gender and jaw differences. DV was less preferred over the traditional procedure in children. © 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Can evidence change the rate of back surgery? A randomized trial of community-based education.

PubMed

Goldberg, H I; Deyo, R A; Taylor, V M; Cheadle, A D; Conrad, D A; Loeser, J D; Heagerty, P J; Diehr, P

2001-01-01

Timely adoption of clinical practice guidelines is more likely to happen when the guidelines are used in combination with adjuvant educational strategies that address social as well as rational influences. To implement the conservative, evidence-based approach to low-back pain recommended in national guidelines, with the anticipated effect of reducing population-based rates of surgery. A randomized, controlled trial. Ten communities in western Washington State with annual rates of back surgery above the 1990 national average (158 operations per 100,000 adults). Spine surgeons, primary care physicians, patients who were surgical candidates, and hospital administrators. The five communities randomized to the intervention group received a package of six educational activities tailored to local needs by community planning groups. Surgeon study groups, primary care continuing medical education conferences, administrative consensus processes, videodisc-aided patient decision making, surgical outcomes management, and generalist academic detailing were serially implemented over a 30-month intervention period. Quarterly observations of surgical rates. After implementation of the intervention, surgery rates declined in the intervention communities but increased slightly in the control communities. The net effect of the intervention is estimated to be a decline of 20.9 operations per 100,000, a relative reduction of 8.9% (P = 0.01). We were able to use scientific evidence to engender voluntary change in back pain practice patterns across entire communities.

Minilaparotomy vs. laparoscopic cholecystectomy: results of a randomized clinical trial.

PubMed

Velázquez-Mendoza, José Dolores; Villagrán-Murillo, Francisco Javier; González-Ojeda, Alejandro

2012-01-01

Currently, laparoscopic cholecystectomy is considered the gold standard for treatment of gallstones with advantages in regard to postoperative pain, hospital stay, early return to activities of daily living and acceptable cosmetic results. Open cholecystectomy in the form of minilaparotomy may be an effective alternative for the management of symptomatic cholelithiasis. We undertook this study to compare the results of laparoscopic cholecystectomy and minilaparotomy cholecystectomy techniques. methods: We conducted a randomized clinical trial between January 2009 and December 2009. We included patients with symptomatic cholelithiasis divided into two groups: group A--minilaparotomy and group B--laparoscopic cholecystectomy. End-point variables were age, gender, pre- and postoperative diagnosis, operative time, conversion or extension, hospital stay, complications and pain. Statistical analysis included Fisher's exact test, χ(2) test and Student t test. There were 88 patients with cholelithiasis: 37 men and 51 women. Mean age was 45.65 years. There were 45 patients in Group A and 43 patients in Group B. Mean operative time was 79.02 min for minilaparotomy and 86.04 min for laparoscopic cholecystectomy (p = 0.33). Average hospital stay was 2.75 days for minilaparotomy and of 2.02 days for laparoscopy (p = 0.60). Complications of minilaparotomy were demonstrated in 6.6% of patients and for laparoscopic cholecystectomy in 16.3% of patients (p = 0.16). There were three extensions and five conversions. Minilaparotomy cholecystectomy has results similar to laparoscopic cholecystectomy.

Statistical Frequency-Dependent Analysis of Trial-to-Trial Variability in Single Time Series by Recurrence Plots.

PubMed

Tošić, Tamara; Sellers, Kristin K; Fröhlich, Flavio; Fedotenkova, Mariia; Beim Graben, Peter; Hutt, Axel

2015-01-01

For decades, research in neuroscience has supported the hypothesis that brain dynamics exhibits recurrent metastable states connected by transients, which together encode fundamental neural information processing. To understand the system's dynamics it is important to detect such recurrence domains, but it is challenging to extract them from experimental neuroscience datasets due to the large trial-to-trial variability. The proposed methodology extracts recurrent metastable states in univariate time series by transforming datasets into their time-frequency representations and computing recurrence plots based on instantaneous spectral power values in various frequency bands. Additionally, a new statistical inference analysis compares different trial recurrence plots with corresponding surrogates to obtain statistically significant recurrent structures. This combination of methods is validated by applying it to two artificial datasets. In a final study of visually-evoked Local Field Potentials in partially anesthetized ferrets, the methodology is able to reveal recurrence structures of neural responses with trial-to-trial variability. Focusing on different frequency bands, the δ-band activity is much less recurrent than α-band activity. Moreover, α-activity is susceptible to pre-stimuli, while δ-activity is much less sensitive to pre-stimuli. This difference in recurrence structures in different frequency bands indicates diverse underlying information processing steps in the brain.

Statistical Frequency-Dependent Analysis of Trial-to-Trial Variability in Single Time Series by Recurrence Plots

PubMed Central

Tošić, Tamara; Sellers, Kristin K.; Fröhlich, Flavio; Fedotenkova, Mariia; beim Graben, Peter; Hutt, Axel

2016-01-01

For decades, research in neuroscience has supported the hypothesis that brain dynamics exhibits recurrent metastable states connected by transients, which together encode fundamental neural information processing. To understand the system's dynamics it is important to detect such recurrence domains, but it is challenging to extract them from experimental neuroscience datasets due to the large trial-to-trial variability. The proposed methodology extracts recurrent metastable states in univariate time series by transforming datasets into their time-frequency representations and computing recurrence plots based on instantaneous spectral power values in various frequency bands. Additionally, a new statistical inference analysis compares different trial recurrence plots with corresponding surrogates to obtain statistically significant recurrent structures. This combination of methods is validated by applying it to two artificial datasets. In a final study of visually-evoked Local Field Potentials in partially anesthetized ferrets, the methodology is able to reveal recurrence structures of neural responses with trial-to-trial variability. Focusing on different frequency bands, the δ-band activity is much less recurrent than α-band activity. Moreover, α-activity is susceptible to pre-stimuli, while δ-activity is much less sensitive to pre-stimuli. This difference in recurrence structures in different frequency bands indicates diverse underlying information processing steps in the brain. PMID:26834580

Integrated Design of a Telerobotic Workstation

NASA Technical Reports Server (NTRS)

Rochlis, Jennifer L.; Clarke, John-Paul

2001-01-01

The experiments described in this paper are part of a larger joint MIT/NASA research effort that focuses on the development of a methodology for designing and evaluating integrated interfaces for highly dexterous and multi-functional telerobots. Specifically, a telerobotic workstation is being designed for an Extravehicular Activity (EVA) anthropomorphic space station telerobot. Previous researchers have designed telerobotic workstations based upon performance of discrete subsets of tasks (for example, peg-in-hole, tracking, etc.) without regard for transitions that operators go through between tasks performed sequentially in the context of larger integrated tasks. The exploratory research experiments presented here took an integrated approach and assessed how subjects operating a full-immersion telerobot perform during the transitions between sub-tasks of two common EVA tasks. Preliminary results show that up to 30% of total task time is spent gaining and maintaining Situation Awareness (SA) of their task space and environment during transitions. Although task performance improves over the two trial days, the percentage of time spent on SA remains the same. This method identifies areas where workstation displays and feedback mechanisms are most needed to increase operator performance and decrease operator workload - areas that previous research methods have not been able to address.

Rib fractures in trauma patients: does operative fixation improve outcome?

PubMed

Majak, Peter; Næss, Pål A

2016-12-01

Renewed interest in surgical fixation of rib fractures has emerged. However, conservative treatment is still preferred at most surgical departments. We wanted to evaluate whether operative treatment of rib fractures may benefit severely injured patients. Several studies report a reduction in mechanical ventilation time, ICU length of stay (LOS), hospital LOS, pneumonia, need for tracheostomy, pain and costs in operatively treated patients with multiple rib fractures compared with patients treated nonoperatively. Although patient selection and timing of the operation seem crucial for successful outcome, no consensus exists. Mortality reduction has only been shown in a few studies. Most studies are retrospective cohort and case-control studies. Only four randomized control trials exist. Conservative treatment, consisting of respiratory assistance and pain control, is still the treatment of choice in the vast majority of patients with multiple rib fractures. In selected patients, operative fixation of fractured ribs within 72 h postinjury may lead to better outcome. More randomized control trials are needed to further determine who benefits from surgical fixation of rib fractures.

Physical activity programs for promoting bone mineralization and growth in preterm infants.

PubMed

Schulzke, Sven M; Kaempfen, Siree; Trachsel, Daniel; Patole, Sanjay K

2014-04-22

Lack of physical stimulation may contribute to metabolic bone disease of preterm infants, resulting in poor bone mineralization and growth. Physical activity programs combined with adequate nutrition might help to promote bone mineralization and growth. The primary objective was to assess whether physical activity programs in preterm infants improve bone mineralization and growth and reduce the risk of fracture.The secondary objectives included other potential benefits in terms of length of hospital stay, skeletal deformities and neurodevelopmental outcomes, and adverse events.Subgroup analysis:• Given that the smallest infants are most vulnerable for developing osteopenia (Bishop 1999), a subgroup analysis was planned for infants with birth weight < 1000 g.• Calcium and phosphorus intake may affect an infant's ability to increase bone mineral content (Kuschel 2004). Therefore, an additional subgroup analysis was planned for infants receiving different amounts of calcium and phosphorus, along with full enteral feeds as follows. ∘ Below 100 mg/60 mg calcium/phosphorus or equal to/above 100 mg/60 mg calcium/phosphorus per 100 mL milk. ∘ Supplementation of calcium without phosphorus. ∘ Supplementation of phosphorus without calcium. The standard search strategy of the Cochrane Neonatal Review Group (CNRG) was used. The search included the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 9), MEDLINE, EMBASE, CINAHL (1966 to March 2013), and cross-references, as well as handsearching of abstracts of the Society for Pediatric Research and the International Journal of Sports Medicine. Randomized and quasi-randomized controlled trials comparing physical activity programs (extension and flexion, range-of-motion exercises) versus no organized physical activity programs in preterm infants. Data collection, study selection, and data analysis were performed according to the methods of the CNRG. Eleven trials enrolling 324 preterm infants (gestational age 26 to 34 weeks) were included in this review. All were small (N = 16 to 50) single-center studies that evaluated daily physical activity for three and one-half to eight weeks during initial hospitalization. Methodological quality and reporting of included trials were variable.Four trials demonstrated moderate short-term benefits of physical activity for bone mineralization at completion of the physical activity program. The only trial assessing long-term effects on bone mineralization showed no effect of physical activity administered during initial hospitalization on bone mineralization at 12 months corrected age. Meta-analysis from four trials demonstrated a positive effect of physical activity on daily weight gain (weighted mean difference (WMD) 2.21 g/kg/d, 95% confidence interval (CI) 1.23 to 3.19). Data from four trials showed a positive effect on linear growth (WMD 0.12 cm/wk, 95% CI 0.01 to 0.24) but not on head growth (WMD -0.03 cm/wk, 95% CI -0.14 to 0.08) during the study period. Only one trial reported on fractures (this outcome did not occur in intervention and control groups) and complications of preterm birth (no significant differences between intervention and control groups). None of the trials assessed other outcomes relevant to this review. Some evidence suggests that physical activity programs might promote short-term weight gain and bone mineralization in preterm infants. Data are inadequate to allow assessment of harm or long-term effects. Current evidence does not support the routine use of physical activity programs in preterm infants. Further trials incorporating infants with a high baseline risk of osteopenia are required. These trials should address adverse events, long-term outcomes, and the effects of nutritional intake (calories, protein, calcium, phosphorus).

India's growing participation in global clinical trials.

PubMed

Gupta, Yogendra K; Padhy, Biswa M

2011-06-01

Lower operational costs, recent regulatory reforms and several logistic advantages make India an attractive destination for conducting clinical trials. Efforts for maintaining stringent ethical standards and the launch of Pharmacovigilance Program of India are expected to maximize the potential of the country for clinical research. Copyright © 2011. Published by Elsevier Ltd.

[Experimental investigations of coagulation possibilities of noncoherent optico-electronic systems in operations on parenchymatous organs].

PubMed

Sukhin, I A; Furmanov, Iu O; Kozhukhar, O T; Savits'ka, I M; Kachan, S H; Bililovets', O M; Savits'kiĭ, O V

2012-03-01

Results of experimental investigation on elaboration and trial of surgical hemostasis method, using the quartz heating optic noncoherent irradiators of light, are adduced. Basing on analysis of the results obtained, the apparatus for photooptic coagulation was elaborated and trialed on experimental animals.

Impact of Personalised Feedback about Physical Activity on Change in Objectively Measured Physical Activity (the FAB Study): A Randomised Controlled Trial

PubMed Central

Godino, Job G.; Watkinson, Clare; Corder, Kirsten; Marteau, Theresa M.; Sutton, Stephen; Sharp, Stephen J.; Griffin, Simon J.; van Sluijs, Esther M. F.

2013-01-01

Background Low levels of physical activity are a major public health concern, and interventions to promote physical activity have had limited success. Whether or not personalised feedback about physical activity following objective measurement motivates behaviour change has yet to be rigorously examined. Methods And Findings: In a parallel group, open randomised controlled trial, 466 healthy adults aged 32 to 54 years were recruited from the ongoing population-based Fenland Study (Cambridgeshire, UK). Participants were randomised to receive either no feedback until the end of the trial (control group, n=120) or one of three different types of feedback: simple, visual, or contextualised (intervention groups, n=346). The primary outcome was physical activity (physical activity energy expenditure (PAEE) in kJ/kg/day and average body acceleration (ACC) in m/s2) measured objectively using a combined heart rate monitor and accelerometer (Actiheart®). The main secondary outcomes included self-reported physical activity, intention to increase physical activity, and awareness of physical activity (the agreement between self-rated and objectively measured physical activity). At 8 weeks, 391 (83.9%) participants had complete physical activity data. The intervention had no effect on objectively measured physical activity (PAEE: β=-0.92, 95% CI=-3.50 to 1.66, p=0.48 and ACC: β=0.01, 95% CI=-0.00 to 0.02, p=0.21), self-reported physical activity (β=-0.39, 95% CI=-1.59 to 0.81), or intention to increase physical activity (β=-0.05, 95% CI=-0.22 to 0.11). However, it was associated with an increase in awareness of physical activity (OR=1.74, 95% CI=1.05 to 2.89). Results did not differ according to the type of feedback. Conclusions Personalised feedback about physical activity following objective measurement increased awareness but did not result in changes in physical activity in the short term. Measurement and feedback may have a role in promoting behaviour change but are ineffective on their own. Trial Registration Current Controlled Trials ISRCTN92551397 http://www.controlled-trials.com/ISRCTN92551397 PMID:24066178

The efficacy of virtual reality simulation training in laparoscopy: a systematic review of randomized trials.

PubMed

Larsen, Christian Rifbjerg; Oestergaard, Jeanett; Ottesen, Bent S; Soerensen, Jette Led

2012-09-01

Virtual reality (VR) simulators for surgical training might possess the properties needed for basic training in laparoscopy. Evidence for training efficacy of VR has been investigated by research of varying quality over the past decade. To review randomized controlled trials regarding VR training efficacy compared with traditional or no training, with outcome measured as surgical performance in humans or animals. In June 2011 Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science and Google Scholar were searched using the following medical subject headings (MeSh) terms: Laparoscopy/standards, Computing methodologies, Programmed instruction, Surgical procedures, Operative, and the following free text terms: Virtual real* OR simulat* AND Laparoscop* OR train* Controlled trials. All randomized controlled trials investigating the effect of VR training in laparoscopy, with outcome measured as surgical performance. A total of 98 studies were screened, 26 selected and 12 included, with a total of 241 participants. Operation time was reduced by 17-50% by VR training, depending on simulator type and training principles. Proficiency-based training appeared superior to training based on fixed time or fixed numbers of repetition. Simulators offering training for complete operative procedures came out as more efficient than simulators offering only basic skills training. Skills in laparoscopic surgery can be increased by proficiency-based procedural VR simulator training. There is substantial evidence (grade IA - IIB) to support the use of VR simulators in laparoscopic training. © 2012 The Authors  Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Treatment of acute diverticulitis laparoscopic lavage vs. resection (DILALA): study protocol for a randomised controlled trial.

PubMed

Thornell, Anders; Angenete, Eva; Gonzales, Elisabeth; Heath, Jane; Jess, Per; Läckberg, Zoltan; Ovesen, Henrik; Rosenberg, Jacob; Skullman, Stefan; Haglind, Eva

2011-08-01

Perforated diverticulitis is a condition associated with substantial morbidity. Recently published reports suggest that laparoscopic lavage has fewer complications and shorter hospital stay. So far no randomised study has published any results. DILALA is a Scandinavian, randomised trial, comparing laparoscopic lavage (LL) to the traditional Hartmann's Procedure (HP). Primary endpoint is the number of re-operations within 12 months. Secondary endpoints consist of mortality, quality of life (QoL), re-admission, health economy assessment and permanent stoma. Patients are included when surgery is required. A laparoscopy is performed and if Hinchey grade III is diagnosed the patient is included and randomised 1:1, to either LL or HP. Patients undergoing LL receive > 3L of saline intraperitoneally, placement of pelvic drain and continued antibiotics. Follow-up is scheduled 6-12 weeks, 6 months and 12 months. A QoL-form is filled out on discharge, 6- and 12 months. Inclusion is set to 80 patients (40+40). HP is associated with a high rate of complication. Not only does the primary operation entail complications, but also subsequent surgery is associated with a high morbidity. Thus the combined risk of treatment for the patient is high. The aim of the DILALA trial is to evaluate if laparoscopic lavage is a safe, minimally invasive method for patients with perforated diverticulitis Hinchey grade III, resulting in fewer re-operations, decreased morbidity, mortality, costs and increased quality of life. British registry (ISRCTN) for clinical trials ISRCTN82208287http://www.controlled-trials.com/ISRCTN82208287.

Short-term outcomes of local infiltration anaesthetic in total knee arthroplasty: a randomized controlled double-blinded controlled trial.

PubMed

Mulford, Jonathan S; Watson, Anna; Broe, David; Solomon, Michael; Loefler, Andreas; Harris, Ian

2016-03-01

The primary objective of the study was to determine if local infiltration anaesthetic (LIA) reduced total length of hospital stay in total knee arthroplasty (TKA) patients. The study also examined whether LIA improves early pain management, patient satisfaction and range of motion in TKA patients. We conducted a randomized controlled double-blinded study. Fifty patients undergoing TKA were randomized to receive either placebo or LIA at the time of surgery and on the first day post-operatively. Pain scores, level of satisfaction and range of motion were recorded preoperatively and post-operatively. There was no statistical difference between the groups for length of stay, post-operative pain scores, satisfaction scores or range of motion 6 weeks post-operatively. This randomized double-blinded trial did not demonstrate a decrease in pain or reduction of length of stay due to local infiltration analgesia. © 2015 Royal Australasian College of Surgeons.

Non-operative management of posterior tibialis tendon dysfunction: design of a randomized clinical trial [NCT00279630

PubMed Central

Kulig, Kornelia; Pomrantz, Amy B; Burnfield, Judith M; Reischl, Stephen F; Mais-Requejo, Susan; Thordarson, David B; Smith, Ronald W

2006-01-01

Background Posterior tibialis tendon dysfunction (PTTD) is a common cause of foot pain and dysfunction in adults. Clinical observations strongly suggest that the condition is progressive. There are currently no controlled studies evaluating the effectiveness of exercise, orthoses, or orthoses and exercise on Stage I or IIA PTTD. Our study will explore the effectiveness of an eccentric versus concentric strengthening intervention to results obtained with the use of orthoses alone. Findings from this study will guide the development of more efficacious PTTD intervention programs and contribute to enhanced function and quality of life in persons with posterior tibialis tendon dysfunction. Methods/design This paper presents the rationale and design for a randomized clinical trial evaluating the effectiveness of a treatment regime for the non-operative management of Stage I or IIA PTTD. Discussion We have presented the rationale and design for an RCT evaluating the effectiveness of a treatment regimen for the non-operative management of Stage I or IIA PTTD. The results of this trial will be presented as soon as they are available. PMID:16756656

Hydrodynamic cavitation as a novel approach for pretreatment of oily wastewater for anaerobic co-digestion with waste activated sludge.

PubMed

Habashi, Nima; Mehrdadi, Nasser; Mennerich, Artur; Alighardashi, Abolghasem; Torabian, Ali

2016-07-01

Application of hydrodynamic cavitation (HC) was investigated with the objective of biogas production enhancement from co-digestion of oily wastewater (OWW) and waste activated sludge (WAS). Initially, the effect of HC on the OWW was evaluated in terms of energy consumption and turbidity increase. Then, several mixtures of OWW (with and without HC pretreatment) and WAS with the same concentration of total volatile solid were prepared as a substrate for co-digestion. Following, several batch co-digestion trials were conducted. To compare the biogas production, a number of digestion trials were also conducted with a mono substrate (OWW or WAS alone). The best operating condition of HC was achieved in the shortest retention time (7.5 min) with the application of 3mm diameter orifice and maximum pump rotational speed. Biogas production from all co-digestion reactors was higher than the WAS mono substrate reactors. Moreover, biogas production had a direct relationship with OWW ratio and no major inhibition was observed in any of the reactors. The biogas production was also enhanced by HC pretreatment and almost all of the reactors with HC pretreatment had higher reaction rates than the reactors without pretreatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Trial Watch: Toll-like receptor agonists for cancer therapy.

PubMed

Vacchelli, Erika; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2013-08-01

Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of Salmonella minnesota that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of OncoImmunology , we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists.

Effects of a home-based physical rehabilitation program on physical disability after hip fracture: a randomized controlled trial.

PubMed

Edgren, Johanna; Salpakoski, Anu; Sihvonen, Sanna E; Portegijs, Erja; Kallinen, Mauri; Arkela, Marja; Jäntti, Pirkko; Vanhatalo, Jukka; Pekkonen, Mika; Rantanen, Taina; Heinonen, Ari; Sipilä, Sarianna

2015-04-01

Fewer than half of the patients with hip fracture will regain the prefracture level of physical functioning. This secondary analysis of a randomized controlled trial investigated the effects of a multicomponent home-based rehabilitation program (ProMo) on physical disability after hip fracture. Randomized, controlled, parallel-group trial. Rehabilitation in participants' homes; measurements in university-based laboratory and local hospital. Population-based clinical sample of community-dwelling people older than 60 years (n = 81) operated for hip fracture were randomized into intervention and control groups. The year-long intervention aimed at restoring mobility. It included evaluation and modification of environmental hazards, guidance for safe walking, pain management, home exercise, physical activity counseling, and standard care. Physical disability was assessed by a questionnaire at baseline, and 3, 6, and 12 months thereafter. Sum scores were computed for basic (ADLs) and instrumental activities of daily living (IADLs). A higher score indicated more difficulty. GEE models were constructed to analyze the effect of the intervention. In the intention-to-treat analysis, no intervention effect was observed for sum scores. For the single disability items, borderline significant positive effects were observed for preparing food and handling medication (interaction P = .061 and P = .061, respectively). In the per-protocol analysis, the mean differences between groups were -0.4 points (SE 0.5), -1.7 (0.7), and -1.2 (0.7) at 3, 6, and 12 months for ADLs and -1.0 (1.2), -3.2 (1.5), and -2.5 (1.4) for IADLs, correspondingly. The current analyses suggest that home-based rehabilitation may reduce disability among older people after hip fracture. The present results need to be confirmed in a study with larger sample size. Potentially a more task-oriented rehabilitation approach might gain more benefits. Current Controlled Trials (ISRCTN53680197). Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

A Method for Making Cross-Comparable Estimates of the Benefits of Decision Support Technologies for Air Traffic Management

NASA Technical Reports Server (NTRS)

Lee, David; Long, Dou; Etheridge, Mel; Plugge, Joana; Johnson, Jesse; Kostiuk, Peter

1998-01-01

We present a general method for making cross comparable estimates of the benefits of NASA-developed decision support technologies for air traffic management, and we apply a specific implementation of the method to estimate benefits of three decision support tools (DSTs) under development in NASA's advanced Air Transportation Technologies Program: Active Final Approach Spacing Tool (A-FAST), Expedite Departure Path (EDP), and Conflict Probe and Trial Planning Tool (CPTP). The report also reviews data about the present operation of the national airspace system (NAS) to identify opportunities for DST's to reduce delays and inefficiencies.

A randomised study of ilio-inguinal nerve blocks following inguinal hernia repair: a stopped randomised controlled trial.

PubMed

Walker, Stuart; Orlikowski, Chris

2008-02-01

Local anaesthetic use for post-operative pain control is widely used following open inguinal hernia repair but this is not without risk. The aim of this study was to compare ilio-inguinal nerve block and wound irrigation in patients undergoing open inguinal hernia repair under general anaesthetic in a randomised, double blind, placebo controlled trial. Adult patients admitted for unilateral primary open mesh repair of an inguinal hernia were recruited. The patients received a standard general anaesthetic. Prior to skin incision, an ilio-inguinal injection was performed by the anaesthetist with either ropivicaine or normal saline. Prior to closure of the wound, the wound was irrigated with either ropivicaine or normal saline. Post-operatively, all patients received fentynal patient controlled analgesia and regular oral analgesia. Pain scores and visual analogue scores were recorded until discharge. Patients were then contacted by telephone at 24h, 48h, 2weeks and 4weeks post-operatively and asked a standard series of questions, mainly related to post-operative pain. After 12 patients had been recruited the trial was stopped as 5 of the 8 patients who received an ilio-inguinal nerve block suffered a neurological complication. Ilio-inguinal nerve block with ropivicaine should be avoided.

Barriers to the sustainability of an intervention designed to improve patient engagement within NHS mental health rehabilitation units: a qualitative study nested within a randomised controlled trial.

PubMed

Lean, Melanie; Leavey, Gerard; Killaspy, Helen; Green, Nicholas; Harrison, Isobel; Cook, Sarah; Craig, Thomas; Holloway, Frank; Arbuthnott, Maurice; King, Michael

2015-09-02

We undertook a cluster randomised controlled trial to assess the effectiveness of a staff training intervention to improve patient engagement in activities in inpatient mental health rehabilitation units. Concurrently, we undertook a qualitative study to investigate the experiences of staff within the intervention units and the contextual issues that may have influenced the effectiveness of the intervention. We conducted focus groups with staff working in the inpatient units that received the intervention, sampled using a maximum variation strategy. The intervention was accepted by staff. However, the skills gained, and changes to the unit's processes and structures that were agreed with the intervention team were not sustained after they left. The main reasons for this were a) external factors (economic recession, resource limitations); b) organisation level factors (lack of senior staff support; competing priorities); c) limitations of the intervention itself (length of intensive training period; reinforcement of skills). This study illustrates some of the inter-related factors which operate at different levels within and outside of NHS organisations that may impact on the success of complex interventions. These factors need to be considered when designing interventions to ensure adequate buy-in from senior staff. Current Controlled Trials ISRCTN25898179 (Registered 23 April 2010).

Laparoscopic surgery for chronic groin pain in athletes is more effective than nonoperative treatment: a randomized clinical trial with magnetic resonance imaging of 60 patients with sportsman's hernia (athletic pubalgia).

PubMed

Paajanen, Hannu; Brinck, Tuomas; Hermunen, Heikki; Airo, Ilari

2011-07-01

Chronic groin pain in athletes presents often a diagnostic and therapeutic challenge. Sportsman's hernia (also called "athletic pubalgia") is a deficiency of the posterior wall of the inguinal canal, which is often repaired by laparoscopic mesh placement. Endoscopic mesh repair may offer a faster recovery for athletes with sportsman's hernia than nonoperative therapy. A randomized, prospective study was conducted on 60 patients with a diagnosis of chronic groin pain and suspected sportsman's hernia. Clinical data and MRI were collected on all patients. After 3 to 6 months of groin symptoms, the patients were randomized into an operative or a physiotherapy group (n = 30 patients in each group). Operation was performed using a totally extraperitoneal repair in which mesh was placed behind the symphysis and painful groin area. Conservative treatment included at least 2 months of active physiotherapy, including corticosteroid injections and oral anti-inflammatory analgesics. The outcome measures were pre- and postoperative pain using a visual analogue scale and partial or full recovery to sports activity at 1, 3, 6, and 12 months after randomization. The athletes in both treatment groups had similar characteristics and pain scores. Operative repair was more effective than nonoperative treatment to decrease chronic groin pain after 1 month and up to 12 months of follow-up (P < .001). Of the 30 athletes who underwent operation, 27 (90%) returned to sports activities after 3 months of convalescence compared to 8 (27%) of the 30 athletes in the nonoperative group (P < .0001). Of the 30 athletes in the conservatively treated group, 7 (23 %) underwent operation later because of persistent groin pain. This randomized controlled study indicated that the endoscopic placement of retropubic mesh was more efficient than conservative therapy for the treatment of sportsman's hernia (athletic pubalgia). Copyright © 2011 Mosby, Inc. All rights reserved.

Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition

PubMed Central

Kareken, David A.; Dzemidzic, Mario; Wetherill, Leah; Eiler, William; Oberlin, Brandon G.; Harezlak, Jaroslaw; Wang, Yang; O’Connor, Sean J.

2013-01-01

Rationale Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop signal task (SST), which measures the time needed to stop a ballistic hand movement. Objective Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure. Methods Twenty two family history positive (FHP; age = 22.7 years, SD= 1.9) and 18 family history negative (FHN; age = 23.7, SD= 1.8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60mg%, and once during infusion of placebo saline. An independent reference group (n= 13, age= 23.7, SD= 1.8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to ‘Go’ trials that carried no need for inhibition (Inh > Go). Results FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh > Go] activation in FHN subjects, but not in FHP subjects. Within this right frontal cortical region, stop signal reaction time (SSRT) also correlated negatively with [Inh > Go] activation, suggesting that the [Inh > Go] activity was related to inhibitory behavior. Conclusions The results are consistent with the low level of response theory (Schuckit, 1980; Quinn & Fromme, 2011), with FHP being less sensitive to alcohol’s effects. PMID:23468100

Checkpoint inhibitors in endometrial cancer: preclinical rationale and clinical activity.

PubMed

Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Aglietta, Massimo; Genta, Sofia; Valabrega, Giorgio

2017-10-27

Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors. We analyzed all available evidence supporting the role of tumor microenvironment (TME) in EC development and the therapeutic implications offered by immune checkpoint inhibitors in this setting. We performed a review on Pubmed with Mesh keywords 'endometrial cancer' and the name of each checkpoint inhibitor discussed in the article. The same search was operated on clinicaltrial.gov to identify ongoing clinical trials exploring PD-1/PD-L1 and CTLA-4 axis in EC, particularly focusing on POLE-ultra-muted and MSI-H cancer types. POLE-ultra-mutated and MSI-H ECs showed an active TME expressing high number of neo-antigens and an elevated amount of tumor infiltrating lymphocytes (TILs). Preliminary results from a phase-1 clinical trial (KEYNOTE-028) demonstrated antitumor activity of Pembrolizumab in EC. Moreover, both Pembrolizumab and Nivolumab reported durable clinical responses in POLE-ultra-mutated patients. Immune checkpoint inhibitors are an attractive option in POLE-ultra-mutated and MSI-H ECs. Future investigations in these subgroups include combinations of checkpoints inhibitors with chemotherapy and small tyrosine kinase inhibitors (TKIs) to enhance a more robust intra-tumoral immune response.

The Trial of My Life: Behind the Scenes at Operation Greylord.

ERIC Educational Resources Information Center

Sullivan, Thomas P.

1999-01-01

Summarizes the methods and outcomes of Operation Greylord, an undercover operation that investigated the corruption of the Chicago (Illinois) court system. Shows that judges, lawyers, and police are not above and beyond the law's reach and that there are people who will take risks to ensure the existence of justice. (CMK)

Association of socioeconomic, school-related and family factors and physical activity and sedentary behaviour among adolescents: multilevel analysis of the PRALIMAP trial inclusion data.

PubMed

Langlois, Johanne; Omorou, Abdou Y; Vuillemin, Anne; Briançon, Serge; Lecomte, Edith

2017-02-08

Social differences among adolescents in physical activity and sedentary behaviour have been identified but are not well explained. The current study aimed to identify socioeconomic, family and school-related associated factors with physical activity and sedentary behaviour among high-school adolescents. This was a cross-sectional analysis of T0 physical activity and sedentary behaviour of 2523 students 14 - 18 years old recruited for the PRALIMAP trial from 24 French state-run high schools. Data were collected by self-administered questionnaire at the start of grade 10. Adolescents completed the International Physical Activity Questionnaire for physical activity and sedentary behaviour and an ad hoc questionnaire for active commuting and sport participation. Statistical analyses involved linear and logistic regressions. Socioeconomic, family or school variables were associated with levels of physical activity and sedentary behaviour for both boys and girls, but no factor, except perceived parental physical activity level, was associated with total energy expenditure (total physical activity) for either gender. Adolescents with privileged and less privileged socioeconomic status reported the same total amount of energy expenditure. Total physical activity score alone is not sufficient to assess the physical activity of adolescents. These findings may have implications for better understanding of social inequalities in this context and recommendations to prevent overweight. This trial is registered at ClinicalTrials.gov ( NCT00814554 ). The date of registration: 23 December 2008. Registration was not required at the time of the start of PRALIMAP for public health and prevention programmes and trials.

Gating of neural error signals during motor learning

PubMed Central

Kimpo, Rhea R; Rinaldi, Jacob M; Kim, Christina K; Payne, Hannah L; Raymond, Jennifer L

2014-01-01

Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreases in the gain of the vestibulo-ocular reflex (VOR). During VOR-increase training, climbing fiber activity on one trial predicted changes in cerebellar output on the next trial, and optogenetic activation of climbing fibers to mimic their encoding of performance errors was sufficient to implant a motor memory. In contrast, during VOR-decrease training, there was no trial-by-trial correlation between climbing fiber activity and changes in cerebellar output, and climbing fiber activation did not induce VOR-decrease learning. Our data suggest that the ability of climbing fibers to induce plasticity can be dynamically gated in vivo, even under conditions where climbing fibers are robustly activated by performance errors. DOI: http://dx.doi.org/10.7554/eLife.02076.001 PMID:24755290

The role of evidence, context, and facilitation in an implementation trial: implications for the development of the PARIHS framework

PubMed Central

2013-01-01

Background The case has been made for more and better theory-informed process evaluations within trials in an effort to facilitate insightful understandings of how interventions work. In this paper, we provide an explanation of implementation processes from one of the first national implementation research randomized controlled trials with embedded process evaluation conducted within acute care, and a proposed extension to the Promoting Action on Research Implementation in Health Services (PARIHS) framework. Methods The PARIHS framework was prospectively applied to guide decisions about intervention design, data collection, and analysis processes in a trial focussed on reducing peri-operative fasting times. In order to capture a holistic picture of implementation processes, the same data were collected across 19 participating hospitals irrespective of allocation to intervention. This paper reports on findings from data collected from a purposive sample of 151 staff and patients pre- and post-intervention. Data were analysed using content analysis within, and then across data sets. Results A robust and uncontested evidence base was a necessary, but not sufficient condition for practice change, in that individual staff and patient responses such as caution influenced decision making. The implementation context was challenging, in which individuals and teams were bounded by professional issues, communication challenges, power and a lack of clarity for the authority and responsibility for practice change. Progress was made in sites where processes were aligned with existing initiatives. Additionally, facilitators reported engaging in many intervention implementation activities, some of which result in practice changes, but not significant improvements to outcomes. Conclusions This study provided an opportunity for reflection on the comprehensiveness of the PARIHS framework. Consistent with the underlying tenant of PARIHS, a multi-faceted and dynamic story of implementation was evident. However, the prominent role that individuals played as part of the interaction between evidence and context is not currently explicit within the framework. We propose that successful implementation of evidence into practice is a planned facilitated process involving an interplay between individuals, evidence, and context to promote evidence-informed practice. This proposal will enhance the potential of the PARIHS framework for explanation, and ensure theoretical development both informs and responds to the evidence base for implementation. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (PoISE). PMID:23497438

Rule-Guided Executive Control of Response Inhibition: Functional Topography of the Inferior Frontal Cortex

PubMed Central

Cai, Weidong; Leung, Hoi-Chung

2011-01-01

Background The human inferior frontal cortex (IFC) is a large heterogeneous structure with distinct cytoarchitectonic subdivisions and fiber connections. It has been found involved in a wide range of executive control processes from target detection, rule retrieval to response control. Since these processes are often being studied separately, the functional organization of executive control processes within the IFC remains unclear. Methodology/Principal Findings We conducted an fMRI study to examine the activities of the subdivisions of IFC during the presentation of a task cue (rule retrieval) and during the performance of a stop-signal task (requiring response generation and inhibition) in comparison to a not-stop task (requiring response generation but not inhibition). We utilized a mixed event-related and block design to separate brain activity in correspondence to transient control processes from rule-related and sustained control processes. We found differentiation in control processes within the IFC. Our findings reveal that the bilateral ventral-posterior IFC/anterior insula are more active on both successful and unsuccessful stop trials relative to not-stop trials, suggesting their potential role in the early stage of stopping such as triggering the stop process. Direct countermanding seems to be outside of the IFC. In contrast, the dorsal-posterior IFC/inferior frontal junction (IFJ) showed transient activity in correspondence to the infrequent presentation of the stop signal in both tasks and the left anterior IFC showed differential activity in response to the task cues. The IFC subdivisions also exhibited similar but distinct patterns of functional connectivity during response control. Conclusions/Significance Our findings suggest that executive control processes are distributed across the IFC and that the different subdivisions of IFC may support different control operations through parallel cortico-cortical and cortico-striatal circuits. PMID:21673969

The feasibility of the Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) dietary and physical activity modifications: a qualitative study.

PubMed

Shingler, Ellie; Hackshaw-McGeagh, Lucy; Robles, Luke; Persad, Raj; Koupparis, Anthony; Rowe, Edward; Shiridzinomwa, Constance; Bahl, Amit; Martin, Richard M; Lane, J Athene

2017-03-07

There is increasing evidence that low levels of physical activity and diets low in fruit and vegetables and high in meat and dairy products are risk factors for prostate cancer disease progression. The Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) aimed to assess a diet and physical activity intervention in men undergoing radical prostatectomy for localized prostate cancer. The trial included a qualitative component to explore the experiences of men participating in the trial in order to understand the acceptability of the intervention and data collection methods. We report the qualitative findings of the trial and consider how these can be used to inform future research. PrEvENT involved randomizing men to either a dietary and/or physical activity intervention. Semi-structured interviews were conducted with a purposive sample of 17 men on completion of the 6 month trial. Interviews took place in clinic or as telephone interviews, if requested by the participant, and were audio recorded, transcribed, and analyzed using the thematic-based framework approach. Analysis was conducted throughout the data collection process to allow emergent themes to be further explored in subsequent interviews. Three overarching themes were identified: acceptability of the intervention, acceptability of the data collection methods and trial logistics. Participants were predominantly positive about both the dietary and physical activity interventions and most men found the methods of data collection appropriate. Recommendations for future trials include consideration of alternative physical activity options, such as cycling or gym sessions, increased information on portion sizes, the potential importance of including wives or partners in the dietary change process and the possibility of using the pedometer or other wearable technology as part of the physical activity intervention. We provide insight into the opinions and experiences of the acceptability of the PrEvENT diet and physical activity intervention from the participants themselves. The interventions delivered were acceptable to this sample of participants, as were the data collection methods utilized. We also highlight some considerations for further behavioural change interventions in prostate cancer and other similar populations. ISRCTN, ISRCTN99048944 . Registered on 17 November 2014.

Decision making in healthy participants on the Iowa Gambling Task: new insights from an operant approach.

PubMed

Bull, Peter N; Tippett, Lynette J; Addis, Donna Rose

2015-01-01

The Iowa Gambling Task (IGT) has contributed greatly to the study of affective decision making. However, researchers have observed high inter-study and inter-individual variability in IGT performance in healthy participants, and many are classified as impaired using standard criteria. Additionally, while decision-making deficits are often attributed to atypical sensitivity to reward and/or punishment, the IGT lacks an integrated sensitivity measure. Adopting an operant perspective, two experiments were conducted to explore these issues. In Experiment 1, 50 healthy participants completed a 200-trial version of the IGT which otherwise closely emulated Bechara et al.'s (1999) original computer task. Group data for Trials 1-100 closely replicated Bechara et al.'s original findings of high net scores and preferences for advantageous decks, suggesting that implementations that depart significantly from Bechara's standard IGT contribute to inter-study variability. During Trials 101-200, mean net scores improved significantly and the percentage of participants meeting the "impaired" criterion was halved. An operant-style stability criterion applied to individual data revealed this was likely related to individual differences in learning rate. Experiment 2 used a novel operant card task-the Auckland Card Task (ACT)-to derive quantitative estimates of sensitivity using the generalized matching law. Relative to individuals who mastered the IGT, persistent poor performers on the IGT exhibited significantly lower sensitivity to magnitudes (but not frequencies) of rewards and punishers on the ACT. Overall, our findings demonstrate the utility of operant-style analysis of IGT data and the potential of applying operant concurrent-schedule procedures to the study of human decision making.

Design of the Revascularization With Open Bypass vs Angioplasty and Stenting of the Lower Extremity Trial (ROBUST): a randomized clinical trial.

PubMed

Malas, Mahmoud B; Qazi, Umair; Glebova, Natalia; Arhuidese, Isibor; Reifsnyder, Thomas; Black, James; Perler, Bruce A; Freischlag, Julie A

2014-12-01

To our knowledge, there is no level 1 evidence comparing open bypass with angioplasty and stenting in TransAtlantic Inter-Society Consensus (TASC II) B and C superficial femoral artery lesions. The Revascularization With Open Bypass vs Angioplasty and Stenting of the Lower Extremity Trial (ROBUST) is the first prospective randomized clinical trial comparing both treatments. To report the design of the ROBUST trial. The primary aim of the trial is to compare (1) the patency rate (primary, primary assisted, and secondary patency at 6 and 12 months), (2) improvement of quality of life, (3) clinical improvement (at least 1 Rutherford category), and (4) wound healing and limb salvage in patients presenting with critical limb ischemia; secondary aims include (1) cost-effectiveness by factoring procedure and hospital admission costs including rehabilitation, readmission, and reintervention costs, (2) amputation-free survival, (3) reintervention rate, and (4) 30-day operative mortality, morbidity, and wound and access complications. ROBUST is a prospective randomized clinical trial with the aim to enroll 320 patients with intermittent claudication that does not respond to medical management and patients with critical limb ischemia. The maximum level of medical therapy will be administered using antiplatelet agents and statins, as well as measures to control hypertension and diabetes mellitus. Patients with TASC II B or C lesions are prospectively randomized to receive either femoropopliteal bypass or percutaneous transluminal angioplasty and stenting; patients with TASC II A and D lesions are not randomized and receive percutaneous transluminal angioplasty and stenting or femoropopliteal bypass, respectively. All patients will be evaluated at 1, 6, and 12 months postoperatively with physical examination, ankle brachial index, duplex, and a quality-of-life questionnaire. The trial is actively enrolling participants. At the time of writing, 29 patients have been enrolled; most are male (60%) and white (65%). Providing level 1 evidence, ROBUST may help to establish guidelines for the treatment of superficial femoral artery lesions, eliminate unnecessary procedures, and reduce health care costs. clinicaltrials.gov Identifier: NCT01602159.

Electrophysiological evidence for the involvement of proactive and reactive control in a rewarded stop-signal task.

PubMed

Schevernels, Hanne; Bombeke, Klaas; Van der Borght, Liesbet; Hopf, Jens-Max; Krebs, Ruth M; Boehler, C Nicolas

2015-11-01

Reward availability is known to facilitate various cognitive operations, which is usually studied in cue-based paradigms that allow for enhanced preparation in reward-related trials. However, recent research using tasks that signal reward availability via task-relevant stimuli suggests that reward can also rapidly promote performance independent of global strategic preparation. Notably, this effect was also observed in a reward-related stop-signal task, in which behavioral measures of inhibition speed were found to be shorter in trials signaling reward. Corresponding fMRI results implied that this effect relies on boosted reactive control as indicated by increased activity in the 'inhibition-related network' in the reward-related condition. Here, we used EEG to better characterize transient modulations of attentional processes likely preceding this ultimate implementation of response inhibition. Importantly, such modulations would probably reflect enhanced proactive control in the form of more top-down attention to reward-related features. Counter to the notion that behavioral benefits would rely purely on reactive control, we found increased stop-evoked attentional processing (larger N1 component) on reward-related trials. This effect was accompanied by enhanced frontal P3 amplitudes reflecting successful stopping, and earlier and larger ERP differences between successful and failed stop trials in the reward-related condition. Finally, more global proactive control processes in the form of a reward context modulation of reward-unrelated trials did not have an effect on stopping performance but did influence attentional processing of go stimuli. Together, these results suggest that proactive and reactive processes can interact to bring about stimulus-specific reward benefits when the task precludes differential global preparation. Copyright © 2015 Elsevier Inc. All rights reserved.

Interventions for the prediction and management of chronic postsurgical pain after total knee replacement: systematic review of randomised controlled trials

PubMed Central

Beswick, Andrew D; Wylde, Vikki; Gooberman-Hill, Rachael

2015-01-01

Objectives Total knee replacement can be a successful operation for pain relief. However, 10–34% of patients experience chronic postsurgical pain. Our aim was to synthesise evidence on the effectiveness of applying predictive models to guide preventive treatment, and for interventions in the management of chronic pain after total knee replacement. Setting We conducted a systematic review of randomised controlled trials using appropriate search strategies in the Cochrane Library, MEDLINE and EMBASE from inception to October 2014. No language restrictions were applied. Participants Adult patients receiving total knee replacement. Interventions Predictive models to guide treatment for prevention of chronic pain. Interventions for management of chronic pain. Primary and secondary outcome measures Reporting of specific outcomes was not an eligibility criterion but we sought outcomes relating to pain severity. Results No studies evaluated the effectiveness of predictive models in guiding treatment and improving outcomes after total knee replacement. One study evaluated an intervention for the management of chronic pain. The trial evaluated the use of a botulinum toxin A injection with antinociceptive and anticholinergic activity in 49 patients with chronic postsurgical pain after knee replacement. A single injection provided meaningful pain relief for about 40 days and the authors acknowledged the need for a large trial with repeated injections. No trials of multidisciplinary interventions or individualised treatments were identified. Conclusions Our systematic review highlights a lack of evidence about the effectiveness of prediction and management strategies for chronic postsurgical pain after total knee replacement. As a large number of people are affected by chronic pain after total knee replacement, development of an evidence base about care for these patients should be a research priority. PMID:25967998

Program Director Perceptions of Surgical Resident Training and Patient Care under Flexible Duty Hour Requirements.

PubMed

Saadat, Lily V; Dahlke, Allison R; Rajaram, Ravi; Kreutzer, Lindsey; Love, Remi; Odell, David D; Bilimoria, Karl Y; Yang, Anthony D

2016-06-01

The Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST) trial was a national, cluster-randomized, pragmatic, noninferiority trial of 117 general surgery programs, comparing standard ACGME resident duty hour requirements ("Standard Policy") to flexible, less-restrictive policies ("Flexible Policy"). Participating program directors (PDs) were surveyed to assess their perceptions of patient care, resident education, and resident well-being during the study period. A survey was sent to all PDs of the general surgery residency programs participating in the FIRST trial (N = 117 [100% response rate]) in June and July 2015. The survey compared PDs' perceptions of the duty hour requirements in their arm of the FIRST trial during the study period from July 1, 2014 to June 30, 2015. One hundred percent of PDs in the Flexible Policy arm indicated that residents used their additional flexibility in duty hours to complete operations they started or to stabilize a critically ill patient. Compared with the Standard Policy arm, PDs in the Flexible Policy arm perceived a more positive effect of duty hours on the safety of patient care (68.9% vs 0%; p < 0.001), continuity of care (98.3% vs 0%; p < 0.001), and resident ability to attend educational activities (74.1% vs 3.4%; p < 0.001). Most PDs in both arms reported that safety of patient care (71.8%), continuity of care (94.0%), quality of resident education (83.8%), and resident well-being (55.6%) would be improved with a hypothetical permanent adoption of more flexible duty hours. Program directors involved in the FIRST trial perceived improvements in patient safety, continuity of care, and multiple aspects of resident education and well-being with flexible duty hours. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Neuronal Substrates Underlying Performance Variability in Well-Trained Skillful Motor Task in Humans.

PubMed

Mizuguchi, Nobuaki; Uehara, Shintaro; Hirose, Satoshi; Yamamoto, Shinji; Naito, Eiichi

2016-01-01

Motor performance fluctuates trial by trial even in a well-trained motor skill. Here we show neural substrates underlying such behavioral fluctuation in humans. We first scanned brain activity with functional magnetic resonance imaging while healthy participants repeatedly performed a 10 s skillful sequential finger-tapping task. Before starting the experiment, the participants had completed intensive training. We evaluated task performance per trial (number of correct sequences in 10 s) and depicted brain regions where the activity changes in association with the fluctuation of the task performance across trials. We found that the activity in a broader range of frontoparietocerebellar network, including the bilateral dorsolateral prefrontal cortex (DLPFC), anterior cingulate and anterior insular cortices, and left cerebellar hemisphere, was negatively correlated with the task performance. We further showed in another transcranial direct current stimulation (tDCS) experiment that task performance deteriorated, when we applied anodal tDCS to the right DLPFC. These results indicate that fluctuation of brain activity in the nonmotor frontoparietocerebellar network may underlie trial-by-trial performance variability even in a well-trained motor skill, and its neuromodulation with tDCS may affect the task performance.

A systematic review and meta-analysis of randomized controlled trials comparing hysteroscopic morcellation with resectoscopy for patients with endometrial lesions.

PubMed

Li, Chunbo; Dai, Zhiyuan; Gong, Yuping; Xie, Bingying; Wang, Bei

2017-01-01

Results on the efficacy of hysteroscopic morcellation for patients with endometrial lesions remain conflicting. To compare hysteroscopic morcellation with conventional resectoscopy for removal of endometrial lesions. Electronic databases were searched for reports published up to February 1, 2016, using terms such as "morcellator," "morcellators," "morcellate," "morcellation," "morcellated," "hysteroscopy," "hysteroscopy," "uteroscope," and "transcervical." Randomized controlled trials were included if they assessed success rate, procedure speed, complications, tolerability, and/or learning curve. Data were extracted by two independent reviewers and a meta-analysis was performed. Four trials including 392 patients were analyzed. Successful removal of all endometrial lesions was more frequent with hysteroscopic morcellation than conventional resectoscopy (odds ratio 4.49, 95% confidence interval [CI] 1.94-10.41; P<0.001). Total operative time was also shorter with hysteroscopic morcellation (mean difference -4.94 minutes, 95% CI -7.20 to -2.68; P<0.001). No significant differences in complications were found. Meta-analyses were not possible for tolerability and learning curve. In one study, hysteroscopic morcellation was acceptable to more patients (P=0.009). Hysteroscopic morcellation is associated with a higher operative success rate and a shorter operative time among patients with endometrial lesions than is resectoscopy. More high-quality trials are required to validate these results. © 2016 International Federation of Gynecology and Obstetrics.

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

DTIC Science & Technology

2002-08-01

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

Demonstration and field trial of a resilient hybrid NG-PON test-bed

NASA Astrophysics Data System (ADS)

Prat, Josep; Polo, Victor; Schrenk, Bernhard; Lazaro, Jose A.; Bonada, Francesc; Lopez, Eduardo T.; Omella, Mireia; Saliou, Fabienne; Le, Quang T.; Chanclou, Philippe; Leino, Dmitri; Soila, Risto; Spirou, Spiros; Costa, Liliana; Teixeira, Antonio; Tosi-Beleffi, Giorgio M.; Klonidis, Dimitrios; Tomkos, Ioannis

2014-10-01

A multi-layer next generation PON prototype has been built and tested, to show the feasibility of extended hybrid DWDM/TDM-XGPON FTTH networks with resilient optically-integrated ring-trees architecture, supporting broadband multimedia services. It constitutes a transparent common platform for the coexistence of multiple operators sharing the optical infrastructure of the central metro ring, passively combining the access and the metropolitan network sections. It features 32 wavelength connections at 10 Gbps, up to 1000 users distributed in 16 independent resilient sub-PONs over 100 km. This paper summarizes the network operation, demonstration and field trial results.

Information need in local government and online network system ; LOGON

NASA Astrophysics Data System (ADS)

Ohta, Masanori

Local Authorities Systems DEvelopment Center started the trial operation of LOcal Government information service On-line Network system (LOGON) in April of 1988. Considering the background of LOGON construction this paper introduces the present status of informationalization in municipalities and needs to network systems as well as information centers based on results of various types of research. It also compares database systems with communication by personal computers, both of which are typical communication forms, and investigates necessary functions of LOGON. The actual system functions, services and operation of LOGON and some problems occurred in the trial are discussed.

Randomised clinical trial: prucalopride, a colonic pro-motility agent, reduces the duration of post-operative ileus after elective gastrointestinal surgery.

PubMed

Gong, J; Xie, Z; Zhang, T; Gu, L; Yao, W; Guo, Z; Li, Y; Lu, N; Zhu, W; Li, N; Li, J

2016-04-01

Previous studies have shown that recovery of colonic transit is a major determinant of post-operative ileus and clinical recovery after gastrointestinal surgery. Prucalopride is a highly selective 5-hydroxytryptamine receptor-4 agonist with colonic pro-motility effects. To evaluate the effect and safety of prucalopride on post-operative ileus and surgical outcomes after elective gastrointestinal surgery. In this phase II randomised clinical trial, 110 patients undergoing elective gastrointestinal surgery were randomised to either oral prucalopride (2 mg/day) (n = 55) or placebo (n = 55). Intervention was started 24 h after surgery and stopped after defecation or maximally at 7 days. The primary outcome was time to defecation. Secondary outcomes included time to first passage of flatus, tolerance of solid food, nasogastric tube reinsertion, post-operative length of stay, hospital readmission, overall cost, time to walk independently, surgical complications and inflammatory parameters. Patients who received prucalopride had a shorter time to defecation (65.0 vs. 94.5 h, P = 0.001), passage of flatus (53.0 vs. 73.0 h, P < 0.001), and post-operative length of stay (7.0 vs. 8.0 days, P = 0.001) than controls. The number of patients with prolonged ileus (>5 days) (16.4% vs. 34.5%, P = 0.026) and the C-reactive protein level on post-operative day 5 (35.67 vs. 59.07 mg/L, P = 0.040) were lower in the prucalopride group. There was no significant difference in post-operative Clavien-Dindo grade III and IV complications (P = 0.606) between the groups. Prucalopride is a safe and effective treatment to reduce post-operative ileus and systemic inflammation without affecting post-operative complications in patients undergoing elective gastrointestinal surgery. ClinicalTrials.gov: NCT02004652. © 2016 John Wiley & Sons Ltd.

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

PubMed

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

2013-11-01

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

Effect of physical activity on frailty and associated negative outcomes: the LIFE randomized trial

USDA-ARS?s Scientific Manuscript database

Background: Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large, long-term, randomized trials are lacking. Objective: To determine whether a long-term structured moderate-intensity physical activity (PA) p...

An active learning approach for rapid characterization of endothelial cells in human tumors.

PubMed

Padmanabhan, Raghav K; Somasundar, Vinay H; Griffith, Sandra D; Zhu, Jianliang; Samoyedny, Drew; Tan, Kay See; Hu, Jiahao; Liao, Xuejun; Carin, Lawrence; Yoon, Sam S; Flaherty, Keith T; Dipaola, Robert S; Heitjan, Daniel F; Lal, Priti; Feldman, Michael D; Roysam, Badrinath; Lee, William M F

2014-01-01

Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers.

Review and meta-analysis of prospective randomized controlled trials (RCTs) comparing laparo-endoscopic single site and multiport laparoscopy in gynecologic operative procedures.

PubMed

Pontis, Alessandro; Sedda, Federica; Mereu, Liliana; Podda, Mauro; Melis, Gian Benedetto; Pisanu, Adolfo; Angioni, Stefano

2016-09-01

To critically appraise published randomized controlled trials (RCTs) comparing laparo-endoscopic single site (LESS) and multi-port laparoscopic (MPL) in gynecologic operative surgery; the aim was to assess feasibility, safety, and potential benefits of LESS in comparison to MPL. A systematic review and meta-analysis of eleven RCTs. Women undergoing operative LESS and MPL gynecologic procedure (hysterectomy, cystectomy, salpingectomy, salpingo-oophorectomy, myomectomy). Outcomes evaluated were as follows: postoperative overall morbidity, postoperative pain evaluation at 6, 12, 24 and 48 h, cosmetic patient satisfaction, conversion rate, body mass index (BMI), operative time, blood loss, hemoglobin drop, postoperative hospital stay. Eleven RCTs comprising 956 women with gynecologic surgical disease randomized to either LESS (477) or MPL procedures (479) were analyzed systematically. The LESS approach is a surgical procedure with longer operative and better cosmetic results time than MPL but without statistical significance. Operative outcomes, postoperative recovery, postoperative morbidity and patient satisfaction are similar in LESS and MPL. LESS may be considered an alternative to MPL with comparable feasibility and safety in gynecologic operative procedures. However, it does not offer the expected advantages in terms of postoperative pain and cosmetic satisfaction.

Determining optimal clothing ensembles based on weather forecasts, with particular reference to outdoor winter military activities.

PubMed

Morabito, Marco; Pavlinic, Daniela Z; Crisci, Alfonso; Capecchi, Valerio; Orlandini, Simone; Mekjavic, Igor B

2011-07-01

Military and civil defense personnel are often involved in complex activities in a variety of outdoor environments. The choice of appropriate clothing ensembles represents an important strategy to establish the success of a military mission. The main aim of this study was to compare the known clothing insulation of the garment ensembles worn by soldiers during two winter outdoor field trials (hike and guard duty) with the estimated optimal clothing thermal insulations recommended to maintain thermoneutrality, assessed by using two different biometeorological procedures. The overall aim was to assess the applicability of such biometeorological procedures to weather forecast systems, thereby developing a comprehensive biometeorological tool for military operational forecast purposes. Military trials were carried out during winter 2006 in Pokljuka (Slovenia) by Slovene Armed Forces personnel. Gastrointestinal temperature, heart rate and environmental parameters were measured with portable data acquisition systems. The thermal characteristics of the clothing ensembles worn by the soldiers, namely thermal resistance, were determined with a sweating thermal manikin. Results showed that the clothing ensemble worn by the military was appropriate during guard duty but generally inappropriate during the hike. A general under-estimation of the biometeorological forecast model in predicting the optimal clothing insulation value was observed and an additional post-processing calibration might further improve forecast accuracy. This study represents the first step in the development of a comprehensive personalized biometeorological forecast system aimed at improving recommendations regarding the optimal thermal insulation of military garment ensembles for winter activities.

A randomized trial of prewarming on patient satisfaction and thermal comfort in outpatient surgery.

PubMed

Akhtar, Zohaib; Hesler, Brian D; Fiffick, Alexa N; Mascha, Edward J; Sessler, Daniel I; Kurz, Andrea; Ayad, Sabry; Saager, Leif

2016-09-01

To test the primary hypothesis that forced-air prewarming improves patient satisfaction after outpatient surgery and to evaluate the effect on core temperature and thermal comfort. Prospective randomized controlled trial. Preoperative area, operating room, and postanesthesia care unit. A total of 115 patients aged 18 to 75 years with American Society of Anesthesiologists status <4 and body mass index of 15 to 36kg/m(2) who were undergoing outpatient surgery (duration <4 hours). Patients were randomized to active prewarming with a Mistral-Air warming system initially set to 43°C or no active prewarming. All patients were warmed intraoperatively. Demographic and morphometric characteristics, perioperative core temperature, ambient temperature, EVAN-G satisfaction score, thermal comfort via visual analog scales. Data from 102 patients were included in the final analysis. Prewarming did not significantly reduce redistribution hypothermia, with prewarmed minus not prewarmed core temperature differing by only 0.18°C (95% confidence interval [CI], -0.001 to 0.37) during the initial hour of anesthesia (P=.052). Prewarming increased the mean EVAN-G satisfaction score, although not significantly, with an overall difference (prewarmed minus not prewarmed) of 5.6 (95% CI, -0.9 to 12.2; P=.09). Prewarming increased thermal comfort, with an overall difference of 6.6 mm (95% CI, 1.0-12.9; P=.02). Active prewarming increased thermal comfort but did not significantly reduce redistribution hypothermia or improve postoperative patient satisfaction. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Feeding response of sport fish after electrical immobilization, chemical sedation, or both

USGS Publications Warehouse

Meinertz, Jeffery R.; Fredricks, Kim T.; Ambrose, Ryan D.; Jackan, Leanna M.; Wise, Jeremy K.

2012-01-01

Fishery managers frequently capture wild fish for a variety of fishery management activities. Though some activities can be accomplished without immobilizing the fish, others are accomplished more readily, humanely, and safely (for both the handler and the fish) when fish are immobilized by physical (e.g., electrical immobilization) or chemical sedation. A concern regarding the use of chemical sedatives is that chemical residues may remain in the fillet tissue after the fish recovers from sedation. If those residues are harmful to humans, there is some risk that a postsedated fish released to public waters may be caught and consumed by an angler. To characterize this risk, a series of four trials were conducted. Three trials assessed feeding activity after hatchery-reared fish were electrically immobilized, chemically sedated, or both, and one trial assessed the likelihood of an angler catching a wild fish that had been electrically immobilized and chemically sedated. Results from the first trial indicated that the feeding activity of laboratory habituated fish was variable among and within species after electrical immobilization, chemical sedation, or both. Results from the second trial indicated that the resumption of feeding activity was rapid after being mildly sedated for 45 min. Results from the third trial indicated that the feeding activity of outdoor, hatchery-reared fish was relatively aggressive after fish had been chemically sedated. Results from the fourth trial indicated that the probability of capturing wild fish in a more natural environment by angling after fish had been electrically immobilized and chemically sedated is not likely, i.e., in a group of five fish caught, 3 out of 100 times one would be a fish that had been sedated.

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.

Effect of neck flexor muscle activation on impact velocity of the head during backward falls in young adults.

PubMed

Choi, W J; Robinovitch, S N; Ross, S A; Phan, J; Cipriani, D

2017-11-01

Falls are a common cause of traumatic brain injuries (TBI) across the lifespan. A proposed but untested hypothesis is that neck muscle activation influences impact severity and risk for TBI during a fall. We conducted backward falling experiments to test whether activation of the neck flexor muscles facilitates the avoidance of head impact, and reduces impact velocity if the head contacts the ground. Young adults (n=8) fell from standing onto a 30cm thick gymnastics mat while wearing a helmet. Participants were instructed to fall backward and (a) prevent their head from impacting the mat ("no head impact" trials); (b) allow their head to impact the mat, but with minimal impact severity ("soft impact" trials); and (c) allow their head to impact the mat, while inhibiting efforts to reduce impact severity ("hard impact" trials). Trial type associated with peak magnitude of electromyographic activity of the sternocleidomastoid (SCM) muscles (p<0.017), and with the vertical and horizontal velocity of the head at impact (p<0.001). Peak SCM activations, expressed as percent maximal voluntary isometric contraction (%MVIC), averaged 75.3, 67.5, and 44.5%MVIC in "no head impact", "soft impact", and "hard impact" trials, respectively. When compared to "soft impact" trials, vertical impact velocities in "hard impact" trials averaged 87% greater (3.23 versus 1.73m/s) and horizontal velocities averaged 83% greater (2.74 versus 1.50m/s). For every 10% increase in SCM %MVIC, vertical impact velocity decreased 0.24m/s and horizontal velocity decreased 0.22m/s. We conclude that SCM activation contributes to the prevention and modulation of head impact severity during backward falls. Copyright © 2017 Elsevier Ltd. All rights reserved.

Active video games as a tool to prevent excessive weight gain in adolescents: rationale, design and methods of a randomized controlled trial

PubMed Central

2014-01-01

Background Excessive body weight, low physical activity and excessive sedentary time in youth are major public health concerns. A new generation of video games, the ones that require physical activity to play the games –i.e. active games- may be a promising alternative to traditional non-active games to promote physical activity and reduce sedentary behaviors in youth. The aim of this manuscript is to describe the design of a study evaluating the effects of a family oriented active game intervention, incorporating several motivational elements, on anthropometrics and health behaviors in adolescents. Methods/Design The study is a randomized controlled trial (RCT), with non-active gaming adolescents aged 12 – 16 years old randomly allocated to a ten month intervention (receiving active games, as well as an encouragement to play) or a waiting-list control group (receiving active games after the intervention period). Primary outcomes are adolescents’ measured BMI-SDS (SDS = adjusted for mean standard deviation score), waist circumference-SDS, hip circumference and sum of skinfolds. Secondary outcomes are adolescents’ self-reported time spent playing active and non-active games, other sedentary activities and consumption of sugar-sweetened beverages. In addition, a process evaluation is conducted, assessing the sustainability of the active games, enjoyment, perceived competence, perceived barriers for active game play, game context, injuries from active game play, activity replacement and intention to continue playing the active games. Discussion This is the first adequately powered RCT including normal weight adolescents, evaluating a reasonably long period of provision of and exposure to active games. Next, strong elements are the incorporating motivational elements for active game play and a comprehensive process evaluation. This trial will provide evidence regarding the potential contribution of active games in prevention of excessive weight gain in adolescents. Trial registration Dutch Trial register NTR3228. PMID:24661535

A comparison between atmospheric/humidity and vacuum cyanoacrylate fuming of latent fingermarks.

PubMed

Farrugia, Kevin J; Fraser, Joanna; Friel, Lauren; Adams, Duncan; Attard-Montalto, Nicola; Deacon, Paul

2015-12-01

A number of pseudo-operational trials were set up to compare the atmospheric/humidity and vacuum cyanoacrylate fuming processes on plastic carrier bags. The fuming processes were compared using two-step cyanoacrylate fuming with basic yellow 40 (BY40) staining and a one-step fluorescent cyanoacrylate fuming, Lumicyano 4%. Preliminary work using planted fingermarks and split depletions were performed to identify the optimum vacuum fuming conditions. The first pseudo-operational trial compared the different fuming conditions (atmospheric/humidity vs. vacuum) for the two-step process where an additional 50% more marks were detected with the atmospheric/humidity process. None of the marks by the vacuum process could be observed visually; however, a significant number of marks were detected by fluorescence after BY40 staining. The second trial repeated the same work in trial 1 using the one-step cyanoacrylate process, Lumicyano at a concentration of 4%. Trial 2 provided comparable results to trial 1 and all the items were then re-treated with Lumicyano 4% at atmospheric/humidity conditions before dyeing with BY40 to provide the sequences of process A (Lumicyano 4% atmospheric-Lumicyano 4% atmospheric-BY40) and process B (Lumicyano 4% vacuum-Lumicyano 4% atmospheric-BY40). The number of marks (visual and fluorescent) was counted after each treatment with a substantial increase in the number of detected marks in the second and third treatments of the process. The increased detection rate after the double Lumicyano process was unexpected and may have important implications. Trial 3 was performed to investigate whether the amount of cyanoacrylate and/or fuming time had an impact on the results observed in trial 2 whereas trial 4 assessed if the double process using conventional cyanoacrylate, rather than Lumicyano 4%, provided an increased detection rate. Trials 3 and 4 confirmed that doubling the amount of Lumicyano 4% cyanoacrylate and fuming time produced a lower detection rate than the double process with Lumicyano 4%. Furthermore, the double process with conventional cyanoacrylate did not provide any benefit. Scanning electron microscopy was also performed to investigate the morphology of the cyanoacrylate polymer under different conditions. The atmospheric/humidity process appears to be superior to the vacuum process for both the two-step and one-step cyanoacrylate fuming, although the two-step process performed better in comparison to the one-step process under vacuum conditions. Nonetheless, the use of vacuum cyanoacrylate fuming may have certain operational advantages and its use does not adversely affect subsequent cyanoacrylate fuming with atmospheric/humidity conditions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Occupational therapy for patients with problems in personal activities of daily living after stroke: systematic review of randomised trials

PubMed Central

Drummond, Avril; Leonardi-Bee, Jo; Gladman, J R F; Donkervoort, Mireille; Edmans, Judi; Gilbertson, Louise; Jongbloed, Lyn; Logan, Pip; Sackley, Catherine; Walker, Marion; Langhorne, Peter

2007-01-01

Objective To determine whether occupational therapy focused specifically on personal activities of daily living improves recovery for patients after stroke. Design Systematic review and meta-analysis. Data sources The Cochrane stroke group trials register, the Cochrane central register of controlled trials, Medline, Embase, CINAHL, PsycLIT, AMED, Wilson Social Sciences Abstracts, Science Citation Index, Social Science Citation, Arts and Humanities Citation Index, Dissertations Abstracts register, Occupational Therapy Research Index, scanning reference lists, personal communication with authors, and hand searching. Review methods Trials were included if they evaluated the effect of occupational therapy focused on practice of personal activities of daily living or where performance in such activities was the target of the occupational therapy intervention in a stroke population. Original data were sought from trialists. Two reviewers independently reviewed each trial for methodological quality. Disagreements were resolved by consensus. Results Nine randomised controlled trials including 1258 participants met the inclusion criteria. Occupational therapy delivered to patients after stroke and targeted towards personal activities of daily living increased performance scores (standardised mean difference 0.18, 95% confidence interval 0.04 to 0.32, P=0.01) and reduced the risk of poor outcome (death, deterioration or dependency in personal activities of daily living) (odds ratio 0.67, 95% confidence interval 0.51 to 0.87, P=0.003). For every 100 people who received occupational therapy focused on personal activities of daily living, 11 (95% confidence interval 7 to 30) would be spared a poor outcome. Conclusions Occupational therapy focused on improving personal activities of daily living after stroke can improve performance and reduce the risk of deterioration in these abilities. Focused occupational therapy should be available to everyone who has had a stroke. PMID:17901469

Active video games to promote physical activity in children with cancer: a randomized clinical trial with follow-up

PubMed Central

2014-01-01

Background Low levels of physical activity, musculoskeletal morbidity and weight gain are commonly reported problems in children with cancer. Intensive medical treatment and a decline in physical activity may also result in reduced motor performance. Therefore, simple and inexpensive ways to promote physical activity and exercise are becoming an increasingly important part of children’s cancer treatment. Methods The aim of this study is to evaluate the effect of active video games in promotion of physical activity in children with cancer. The research is conducted as a parallel randomized clinical trial with follow-up. Patients between 3 and 16 years old, diagnosed with cancer and treated with vincristine in two specialized medical centers are asked to participate. Based on statistical estimates, the target enrollment is 40 patients. The intervention includes playing elective active video games and, in addition, education and consultations for the family. The control group will receive a general recommendation for physical activity for 30 minutes per day. The main outcomes are the amount of physical activity and sedentary behavior. Other outcomes include motor performance, fatigue and metabolic risk factors. The outcomes are examined with questionnaires, diaries, physical examinations and blood tests at baseline and at 2, 6, 12 and 30 months after the baseline. Additionally, the children’s perceptions of the most enjoyable activation methods are explored through an interview at 2 months. Discussion This trial will help to answer the question of whether playing active video games is beneficial for children with cancer. It will also provide further reasoning for physical activity promotion and training of motor skills during treatment. Trial registration ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012). PMID:24708773

The Impact of Accelerometers on Physical Activity and Weight Loss: A Systematic Review

PubMed Central

Goode, Adam P.; Hall, Katherine S.; Batch, Bryan C.; Huffman, Kim M.; Hastings, S. Nicole; Allen, Kelli D.; Shaw, Ryan J.; Kanach, Frances A.; McDuffie, Jennifer R.; Kosinski, Andrzej S.; Williams, John W.; Gierisch, Jennifer M.

2016-01-01

Background Regular physical activity is important for improving and maintaining health, but sedentary behavior is difficult to change. Providing objective, real-time feedback on physical activity with wearable motion-sensing technologies (activity monitors) may be a promising, scalable strategy to increase physical activity or decrease weight. Purpose We synthesized the literature on the use of wearable activity monitors for improving physical activity and weight-related outcomes and evaluated moderating factors that may have an impact on effectiveness. Methods We searched five databases from January 2000 to January 2015 for peer-reviewed, English-language randomized controlled trials among adults. Random-effects models were used to produce standardized mean differences (SMDs) for physical activity outcomes and mean differences (MDs) for weight outcomes. Heterogeneity was measured with I2. Results Fourteen trials (2,972 total participants) met eligibility criteria; accelerometers were used in all trials. Twelve trials examined accelerometer interventions for increasing physical activity. A small significant effect was found for increasing physical activity (SMD 0.26; 95% CI 0.04 to 0.49; I2=64.7%). Intervention duration was the only moderator found to significantly explain high heterogeneity for physical activity. Eleven trials examined effects of accelerometer interventions on weight. Pooled estimates showed a small significant effect for weight loss (MD −1.65 kg; 95% CI −3.03 to −0.28; I2=81%), and no moderators were significant. Conclusions Accelerometers demonstrated small positive effects on physical activity and weight loss. The small sample sizes with moderate to high heterogeneity in the current studies limit the conclusions that may be drawn. Future studies should focus on how best to integrate accelerometers with other strategies to increase physical activity and weight loss. PMID:27565168

Securing Mobile Networks in an Operational Setting

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Stewart, David H.; Bell, Terry L.; Paulsen, Phillip E.; Shell, Dan

2004-01-01

This paper describes a network demonstration and three month field trial of mobile networking using mobile-IPv4. The network was implemented as part of the US Coast Guard operational network which is a ".mil" network and requires stringent levels of security. The initial demonstrations took place in November 2002 and a three month field trial took place from July through September of 2003. The mobile network utilized encryptors capable of NSA-approved Type 1 algorithms, mobile router from Cisco Systems and 802.11 and satellite wireless links. This paper also describes a conceptual architecture for wide-scale deployment of secure mobile networking in operational environments where both private and public infrastructure is used. Additional issues presented include link costs, placement of encryptors and running routing protocols over layer-3 encryption devices.

The International Remote Monitoring Project: Results of the Swedish Nuclear Power Facility field trial

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

Johnson, C.S.; af Ekenstam, G.; Sallstrom, M.

1995-07-01

The Swedish Nuclear Power Inspectorate (SKI) and the US Department of Energy (DOE) sponsored work on a Remote Monitoring System (RMS) that was installed in August 1994 at the Barseback Works north of Malmo, Sweden. The RMS was designed to test the front end detection concept that would be used for unattended remote monitoring activities. Front end detection reduces the number of video images recorded and provides additional sensor verification of facility operations. The function of any safeguards Containment and Surveillance (C/S) system is to collect information which primarily is images that verify the operations at a nuclear facility. Barsebackmore » is ideal to test the concept of front end detection since most activities of safeguards interest is movement of spent fuel which occurs once a year. The RMS at Barseback uses a network of nodes to collect data from microwave motion detectors placed to detect the entrance and exit of spent fuel casks through a hatch. A video system using digital compression collects digital images and stores them on a hard drive and a digital optical disk. Data and images from the storage area are remotely monitored via telephone from Stockholm, Sweden and Albuquerque, NM, USA. These remote monitoring stations operated by SKI and SNL respectively, can retrieve data and images from the RMS computer at the Barseback Facility. The data and images are encrypted before transmission. This paper presents details of the RMS and test results of this approach to front end detection of safeguard activities.« less

Towards an autonomous sensor architecture for persistent area protection

NASA Astrophysics Data System (ADS)

Thomas, Paul A.; Marshall, Gillian F.; Stubbins, Daniel J.; Faulkner, David A.

2016-10-01

The majority of sensor installations for area protection (e.g. critical national infrastructure, military forward operating bases, etc.) make use of banks of screens each containing one or more sensor feeds, such that the burden of combining data from the various sources, understanding the situation, and controlling the sensors all lies with the human operator. Any automation in the system is generally heavily bespoke for the particular installation, leading to an inflexible system which is difficult to change or upgrade. We have developed a modular system architecture consisting of intelligent autonomous sensor modules, a high level decision making module, a middleware integration layer and an end-user GUI. The modules are all effectively "plug and play", and we have demonstrated that it is relatively simple to incorporate legacy sensors into the architecture. We have extended our previously-reported SAPIENT demonstration system to operate with a larger number and variety of sensor modules, over an extended area, detecting and classifying a wider variety of "threat activities", both vehicular and pedestrian. We report the results of a demonstration of the SAPIENT system containing multiple autonomous sensor modules with a range of modalities including laser scanners, radar, TI, EO, acoustic and seismic sensors. They operate from a combination of mains, generator and battery power, and communicate with the central "hub" over Ethernet, point-to-point wireless links and Wi-Fi. The system has been configured to protect an extended area in a complex semi-urban environment. We discuss the operation of the SAPIENT system in a realistic demonstration environment (which included significant activity not under trial control), showing sensor cueing, multi-modal sensor fusion, threat prioritisation and target hand-off.

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

Hagen Schempf; Daphne D'Zurko

Under funding from the Department of Energy (DOE) and the Northeast Gas Association (NGA), Carnegie Mellon University (CMU) developed an untethered, wireless remote controlled inspection robot dubbed Explorer. The project entailed the design and prototyping of a wireless self-powered video-inspection robot capable of accessing live 6- and 8-inch diameter cast-iron and steel mains, while traversing turns and Ts and elbows under real-time control with live video feedback to an operator. The design is that of a segmented actively articulated and wheel-leg powered robot design, with fisheye imaging capability and self-powered battery storage and wireless real-time communication link. The prototype wasmore » functionally tested in an above ground pipe-network, in order to debug all mechanical, electrical and software subsystems, and develop the necessary deployment and retrieval, as well as obstacle-handling scripts. A pressurized natural gas test-section was used to certify it for operation in natural gas at up to 60 psig. Two subsequent live-main field-trials in both cast-iron and steel pipe, demonstrated its ability to be safely launched, operated and retrieved under real-world conditions. The system's ability to safely and repeatably exidrecover from angled and vertical launchers, traverse multi-thousand foot long pipe-sections, make T and varied-angle elbow-turns while wirelessly sending live video and handling command and control messages, was clearly demonstrated. Video-inspection was clearly shown to be a viable tool to understand the state of this critical buried infrastructure, irrespective of low- (cast-iron) or high-pressure (steel) conditions. This report covers the different aspects of specifications, requirements, design, prototyping, integration and testing and field-trialing of the Explorer platform.« less

Precision of the upgraded cottonscan instrument for measuring the average fiber linear density (fineness) of cotton lint samples

USDA-ARS?s Scientific Manuscript database

An inter-laboratory trial was conducted to validate the operation of the CottonscanTM technology as useful technique for determining the average fiber linear density of cotton. A significant inter-laboratory trial was completed and confirmed that the technology is quite acceptable. For fibers fin...

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

Increasing activity in older adults: A review of the Look AHEAD trial

USDA-ARS?s Scientific Manuscript database

The importance of physical activity for healthy aging has been clearly shown. Evidence from the Look AHEAD trial, a lifestyle intervention for overweight individuals who have type 2 diabetes, provides further evidence for the importance of physical activity. Overall, this intervention provides a pot...

Science Activities for the Visually Impaired: Developing a Model.

ERIC Educational Resources Information Center

DeLucchi, Linda; And Others

1980-01-01

Science activities for the visually impaired (SAVI) introduces blind and visually impaired children (9 to 12 years old) to physical and life sciences in a multisensory way. Evolution of SAVI activities involves exploration, local trials, and national trials. SAVI project materials can help integrate handicapped children into the mainstream through…

The neural coding of creative idea generation across adolescence and early adulthood

PubMed Central

Kleibeuker, Sietske W.; Koolschijn, P. Cédric M. P.; Jolles, Dietsje D.; De Dreu, Carsten K. W.; Crone, Eveline A.

2013-01-01

Creativity is considered key to human prosperity, yet the neurocognitive principles underlying creative performance, and their development, are still poorly understood. To fill this void, we examined the neural correlates of divergent thinking in adults (25–30 years) and adolescents (15–17 years). Participants generated alternative uses (AU) or ordinary characteristics (OC) for common objects while brain activity was assessed using fMRI. Adults outperformed adolescents on the number of solutions for AU and OC trials. Contrasting neural activity for AU with OC trials revealed increased recruitment of left angular gyrus, left supramarginal gyrus, and bilateral middle temporal gyrus in both adults and adolescents. When only trials with multiple AU were included in the analysis, participants showed additional left inferior frontal gyrus (IFG)/middle frontal gyrus (MFG) activation for AU compared to OC trials. Correspondingly, individual difference analyses showed a positive correlation between activations for AU relative to OC trials in left IFG/MFG and divergent thinking performance and activations were more pronounced in adults than in adolescents. Taken together, the results of this study demonstrated that creative idea generation involves recruitment of mainly left lateralized parietal and temporal brain regions. Generating multiple creative ideas, a hallmark of divergent thinking, shows additional lateral PFC activation that is not yet optimized in adolescence. PMID:24416008

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

PubMed

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

2004-03-01

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

Huperzine A for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

PubMed Central

Yang, Guoyan; Wang, Yuyi; Tian, Jinzhou; Liu, Jian-Ping

2013-01-01

Background Huperzine A is a Chinese herb extract used for Alzheimer’s disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer’s disease. Methods We searched for randomized clinical trials (RCTs) of Huperzine A for Alzheimer’s disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249) Results 20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR). One trial demonstrated no significant change in cognitive function as measured by Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and activity of daily living as measured by Alzheimer’s disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A. Conclusions Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials. PMID:24086396

Organizational structure and communication strategies of the bypass angioplasty revascularization investigation: a multicenter clinical trial.

PubMed

Naydeck, B L; Sutton-Tyrrell, K; Burek, K; Sopko, G S

1996-06-01

Efficient communication is a challenge for the many operating components of a multicenter randomized clinical trial. Traditional management theory states that communications generally flow along a path established by a hierarchical organizational structure. A multicenter clinical trial does not fit traditional organizational models well and requires modification of traditional communication techniques. While the scientific community typically views a clinical trial as one large and cohesive enterprise, at each site the trial may actually be conducted as a small project related to the medical specialty of the investigator. Therefore overall trial management must be accomplished through collaboration rather than through direct management. In the Bypass Angioplasty Revascularization Investigation (BARI), the BARI clinical coordinating center has designed and utilized several mechanisms that facilitate effective communication and administrative control of a multicenter clinical trial. These mechanisms provide a framework of communication techniques that accommodate the specific needs of a complex organization.

Effectiveness and cost-effectiveness of a very brief physical activity intervention delivered in NHS Health Checks (VBI Trial): study protocol for a randomised controlled trial.

PubMed

Mitchell, Joanna; Hardeman, Wendy; Pears, Sally; Vasconcelos, Joana C; Prevost, A Toby; Wilson, Ed; Sutton, Stephen

2016-06-27

Physical activity interventions that are targeted at individuals can be effective in encouraging people to be more physically active. However, most such interventions are too long or complex and not scalable to the general population. This trial will test the effectiveness and cost-effectiveness of a very brief physical activity intervention when delivered as part of preventative health checks in primary care (National Health Service (NHS) Health Check). The Very Brief Intervention (VBI) Trial is a two parallel-group, randomised, controlled trial with 1:1 individual allocation and follow-up at 3 months. A total of 1,140 participants will be recruited from 23 primary care practices in the east of England. Participants eligible for an NHS Health Check and who are considered suitable to take part by their doctor and able to provide written informed consent are eligible for the trial. Participants are randomly assigned at the beginning of the NHS Health Check to either 1) the control arm, in which they receive only the NHS Health Check, or 2) the intervention arm, in which they receive the NHS Health Check plus 'Step It Up' (a very brief intervention that can be delivered in 5 minutes by nurses and/or healthcare assistants at the end of the Health Check). 'Step It Up' includes (1) a face-to-face discussion, including feedback on current activity level, recommendations for physical activity, and information on how to use a pedometer, set step goals, and monitor progress; (2) written material supporting the discussion and tips and links to further resources to help increase physical activity; and (3) a pedometer to wear and a step chart for monitoring progress. The primary outcome is accelerometer counts per minute at 3-month follow-up. Secondary outcomes include the time spent in the different levels of physical activity, self-reported physical activity and economic measures. Trial recruitment is underway. The VBI trial will provide evidence on the effectiveness and cost-effectiveness of the Step It Up intervention delivered during NHS Health Checks and will inform policy decisions about introducing very brief interventions into routine primary care practice. ISRCTN Registry, ISRCTN72691150 . Registered on 17 July 2014.

Left Posterior Parietal Cortex Participates in Both Task Preparation and Episodic Retrieval

PubMed Central

Phillips, Jeffrey S.; Velanova, Katerina; Wolk, David A.; Wheeler, Mark E.

2012-01-01

Optimal memory retrieval depends not only on the fidelity of stored information, but also on the attentional state of the subject. Factors such as mental preparedness to engage in stimulus processing can facilitate or hinder memory retrieval. The current study used functional magnetic resonance imaging (fMRI) to distinguish preparatory brain activity before episodic and semantic retrieval tasks from activity associated with retrieval itself. A catch-trial imaging paradigm permitted separation of neural responses to preparatory task cues and memory probes. Episodic and semantic task preparation engaged a common set of brain regions, including the bilateral intraparietal sulcus (IPS), left fusiform gyrus (FG), and the pre-supplementary motor area (pre-SMA). In the subsequent retrieval phase, the left IPS was among a set of frontoparietal regions that responded differently to old and new stimuli. In contrast, the right IPS responded to preparatory cues with little modulation during memory retrieval. The findings support a strong left-lateralization of retrieval success effects in left parietal cortex, and further indicate that left IPS performs operations that are common to both task preparation and memory retrieval. Such operations may be related to attentional control, monitoring of stimulus relevance, or retrieval. PMID:19285142

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

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

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

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

Feasibility, design and conduct of a pragmatic randomized controlled trial to reduce overweight and obesity in children: The electronic games to aid motivation to exercise (eGAME) study

PubMed Central

Maddison, Ralph; Foley, Louise; Ni Mhurchu, Cliona; Jull, Andrew; Jiang, Yannan; Prapavessis, Harry; Rodgers, Anthony; Vander Hoorn, Stephen; Hohepa, Maea; Schaaf, David

2009-01-01

Background Childhood obesity has reached epidemic proportions in developed countries. Sedentary screen-based activities such as video gaming are thought to displace active behaviors and are independently associated with obesity. Active video games, where players physically interact with images onscreen, may have utility as a novel intervention to increase physical activity and improve body composition in children. The aim of the Electronic Games to Aid Motivation to Exercise (eGAME) study is to determine the effects of an active video game intervention over 6 months on: body mass index (BMI), percent body fat, waist circumference, cardio-respiratory fitness, and physical activity levels in overweight children. Methods/Design Three hundred and thirty participants aged 10–14 years will be randomized to receive either an active video game upgrade package or to a control group (no intervention). Discussion An overview of the eGAME study is presented, providing an example of a large, pragmatic randomized controlled trial in a community setting. Reflection is offered on key issues encountered during the course of the study. In particular, investigation into the feasibility of the proposed intervention, as well as robust testing of proposed study procedures is a critical step prior to implementation of a large-scale trial. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12607000632493 PMID:19450288

Targeted rehabilitation to improve outcome after total knee replacement (TRIO): study protocol for a randomised controlled trial.

PubMed

Simpson, A Hamish R W; Hamilton, David F; Beard, David J; Barker, Karen L; Wilton, Timothy; Hutchison, James D; Tuck, Chris; Stoddard, Andrew; Macfarlane, Gary J; Murray, Gordon D

2014-02-01

Approximately 20% of patients are not satisfied with the outcome of total knee replacement, great volumes of which are carried out yearly. Physiotherapy is often provided by the NHS to address dysfunction following knee replacement; however the efficacy of this is unknown. Although clinically it is accepted that therapy is useful, provision of physiotherapy to all patients post-operatively does not enhance outcomes at one year. No study has previously assessed the effect of targeting therapy to individuals struggling to recover in the early post-operative phase.The aim of the TRIO study is to determine whether stratifying care by targeting physiotherapy to those individuals performing poorly following knee replacement is effective in improving the one year outcomes. We are also investigating whether the structure of the physiotherapy provision itself influences outcomes. The study is a multi-centre prospective randomised controlled trial (RCT) of patients undergoing primary total knee replacement, with treatment targeted at those deemed most susceptible to gain from it. Use of the national PROMS programme for pre-operative data collection allows us to screen all patients at initial post-operative clinical review, and recruit only those deemed to be recovering slowly.We aim to recruit 440 patients through various NHS orthopaedic centres who will undergo six weeks of physiotherapy. The intervention will be either 'intensive' involving both hospital and home-based functional exercise rehabilitation, or 'standard of care' consisting of home exercises. Patients will be randomised to either group using a web-based system. Both groups will receive pre and post-intervention physiotherapy review. Patients will be followed-up to one year post-operation. The primary outcome measure is the Oxford Knee Score. Secondary outcomes are patient satisfaction, functional ability, pain scores and cost-effectiveness. Current Controlled Trials ISRCTN23357609. ClinicalTrials.gov NCT01849445.

Aerial Prefeeding Followed by Ground Based Toxic Baiting for More Efficient and Acceptable Poisoning of Invasive Small Mammalian Pests

PubMed Central

Morgan, David; Warburton, Bruce; Nugent, Graham

2015-01-01

Introduced brushtail possums (Trichosurus vulpecula) and rat species (Rattus spp.) are major vertebrate pests in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Aerial distribution of baits containing sodium fluoroacetate (1080) has been refined to maximise cost effectiveness and minimise environmental impact, but this method is strongly opposed by some as it is perceived as being indiscriminate. Although ground based control enables precise placement of baits, operations are often more than twice as costly as aerial control, mainly due to the high labour costs. We investigated a new approach to ground based control that combined aerial distribution of non-toxic ‘prefeed’ baits followed by sparse distribution of toxic baits at regular intervals along the GPS tracked prefeeding flight paths. This approach was tested in two field trials in which both 1080 baits and cholecalciferol baits were used in separate areas. Effectiveness of the approach, assessed primarily using ‘chewcards’, was compared with that of scheduled aerial 1080 operations that were conducted in outlying areas of both trials. Contractors carrying out ground based control were able to follow the GPS tracks of aerial prefeeding flight lines very accurately, and with 1080 baits achieved very high levels of kill of possums and rats similar to those achieved by aerial 1080 baiting. Cholecalciferol was less effective in the first trial, but by doubling the amount of cholecalciferol bait used in the second trial, few possums or rats survived. By measuring the time taken to complete ground baiting from GPS tracks, we predicted that the method (using 1080 baits) would be similarly cost effective to aerial 1080 operations for controlling possums and rats, and considerably less expensive than typical current costs of ground based control. The main limitations to the use of the method will be access to, and size of, the operational site, along with topography and vegetation density. PMID:26218095

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery - the FOCCUS study

PubMed Central

2011-01-01

Introduction Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. Methods This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. Results A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Conclusions Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Trial registration Prospective Clinical Trials, ISRCTN32188676 PMID:22177541

Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients.

PubMed

Fairfield, Cameron; Penninga, Luit; Powell, James; Harrison, Ewen M; Wigmore, Stephen J

2018-04-09

Liver transplantation is an established treatment option for end-stage liver failure. Now that newer, more potent immunosuppressants have been developed, glucocorticosteroids may no longer be needed and their removal may prevent adverse effects. To assess the benefits and harms of glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) or withdrawal versus glucocorticosteroid-containing immunosuppression following liver transplantation. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, Literatura Americano e do Caribe em Ciencias da Saude (LILACS), World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and The Transplant Library until May 2017. Randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal versus glucocorticosteroid-containing immunosuppression for liver transplanted people. Our inclusion criteria stated that participants should have received the same co-interventions. We included trials that assessed complete glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) versus short-term glucocorticosteroids, as well as trials that assessed short-term glucocorticosteroids versus long-term glucocorticosteroids. We used RevMan to conduct meta-analyses, calculating risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables, both with 95% confidence intervals (CIs). We used a random-effects model and a fixed-effect model and reported both results where a discrepancy existed; otherwise we reported only the results from the fixed-effect model. We assessed the risk of systematic errors using 'Risk of bias' domains. We controlled for random errors by performing Trial Sequential Analysis. We presented our results in a 'Summary of findings' table. We included 17 completed randomised clinical trials, but only 16 studies with 1347 participants provided data for the meta-analyses. Ten of the 16 trials assessed complete postoperative glucocorticosteroid avoidance (excluding intra-operative use or treatment of acute rejection) versus short-term glucocorticosteroids (782 participants) and six trials assessed short-term glucocorticosteroids versus long-term glucocorticosteroids (565 participants). One additional study assessed complete post-operative glucocorticosteroid avoidance but could only be incorporated into qualitative analysis of the results due to limited data published in an abstract. All trials were at high risk of bias. Only eight trials reported on the type of donor used. Overall, we found no statistically significant difference for mortality (RR 1.15, 95% CI 0.93 to 1.44; low-quality evidence), graft loss including death (RR 1.15, 95% CI 0.90 to 1.46; low-quality evidence), or infection (RR 0.88, 95% CI 0.73 to 1.05; very low-quality evidence) when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression. Acute rejection and glucocorticosteroid-resistant rejection were statistically significantly more frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 1.33, 95% CI 1.08 to 1.64; low-quality evidence; and RR 2.14, 95% CI 1.13 to 4.02; very low-quality evidence). Diabetes mellitus and hypertension were statistically significantly less frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid-containing immunosuppression (RR 0.81, 95% CI 0.66 to 0.99; low-quality evidence; and RR 0.76, 95% CI 0.65 to 0.90; low-quality evidence). We performed Trial Sequential Analysis for all outcomes. None of the outcomes crossed the monitoring boundaries or reached the required information size. Hence, we cannot exclude random errors from the results of the conventional meta-analyses. Many of the benefits and harms of glucocorticosteroid avoidance or withdrawal remain uncertain because of the limited number of published randomised clinical trials, limited numbers of participants and outcomes, and high risk of bias in the trials. Glucocorticosteroid avoidance or withdrawal appears to reduce diabetes mellitus and hypertension whilst increasing acute rejection, glucocorticosteroid-resistant rejection, and renal impairment. We could identify no other benefits or harms of glucocorticosteroid avoidance or withdrawal. Glucocorticosteroid avoidance or withdrawal may be of benefit in selected patients, especially those at low risk of rejection and high risk of hypertension or diabetes mellitus. The optimal duration of glucocorticosteroid administration remains unclear. More randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal are needed. These should be large, high-quality trials that minimise the risk of random and systematic error.

Thoracic Epidural analgesia versus Rectus Sheath Catheters for open midline incisions in major abdominal surgery within an enhanced recovery programme (TERSC): study protocol for a randomised controlled trial.

PubMed

Wilkinson, Kate M; Krige, Anton; Brearley, Sarah G; Lane, Steven; Scott, Michael; Gordon, Anthony C; Carlson, Gordon L

2014-10-21

Thoracic epidural analgesia (TEA) is recommended for post-operative pain relief in patients undergoing major abdominal surgery via a midline incision. However, the effectiveness of TEA is variable with high failure rates reported post-operatively. Common side effects such as low blood pressure and motor block can reduce mobility and hinder recovery, and a number of rare but serious complications can also occur following their use.Rectus sheath catheters (RSC) may provide a novel alternative approach to somatic analgesia without the associated adverse effects of TEA. The aim of this study is to compare the efficacy of both techniques in terms of pain relief, patient experience, post-operative functional recovery, safety and cost-effectiveness. This is a single-centre randomised controlled non-blinded trial, which also includes a nested qualitative study. Over a two-year period, 132 patients undergoing major abdominal surgery via a midline incision will be randomised to receive either TEA or RSC for post-operative analgesia. The primary outcome measures pain scores on moving from a supine to a sitting position at 24 hours post wound closure, and the patient experience between groups evaluated through in-depth interviews. Secondary outcomes include pain scores at rest and on movement at other time points, opiate consumption, functional recovery, morbidity and cost-effectiveness. This will be the first randomised controlled trial comparing thoracic epidurals to ultrasound-guided rectus sheath catheters in adults undergoing elective midline laparotomy. The standardised care provided by an Enhanced Recovery Programme makes this a comparison between two complex pain packages and not simply two analgesic techniques, in order to ascertain if RSC is a viable alternative to TEA. Current Controlled Trials ISRCTN81223298 (16 January 2014).

Personalised Hip Therapy: development of a non-operative protocol to treat femoroacetabular impingement syndrome in the FASHIoN randomised controlled trial

PubMed Central

Wall, Peter DH; Dickenson, Edward J; Robinson, David; Hughes, Ivor; Realpe, Alba; Hobson, Rachel; Griffin, Damian R; Foster, Nadine E

2016-01-01

Introduction Femoroacetabular impingement (FAI) syndrome is increasingly recognised as a cause of hip pain. As part of the design of a randomised controlled trial (RCT) of arthroscopic surgery for FAI syndrome, we developed a protocol for non-operative care and evaluated its feasibility. Methods In phase one, we developed a protocol for non-operative care for FAI in the UK National Health Service (NHS), through a process of systematic review and consensus gathering. In phase two, the protocol was tested in an internal pilot RCT for protocol adherence and adverse events. Results The final protocol, called Personalised Hip Therapy (PHT), consists of four core components led by physiotherapists: detailed patient assessment, education and advice, help with pain relief and an exercise-based programme that is individualised, supervised and progressed over time. PHT is delivered over 12–26 weeks in 6–10 physiotherapist-patient contacts, supplemented by a home exercise programme. In the pilot RCT, 42 patients were recruited and 21 randomised to PHT. Review of treatment case report forms, completed by physiotherapists, showed that 13 patients (62%) received treatment that had closely followed the PHT protocol. 13 patients reported some muscle soreness at 6 weeks, but there were no serious adverse events. Conclusion PHT provides a structure for the non-operative care of FAI and offers guidance to clinicians and researchers in an evolving area with limited evidence. PHT was deliverable within the National Health Service, is safe, and now forms the comparator to arthroscopic surgery in the UK FASHIoN trial (ISRCTN64081839). Trial registration number ISRCTN 09754699. PMID:27629405

The Clavicle Trial: A Multicenter Randomized Controlled Trial Comparing Operative with Nonoperative Treatment of Displaced Midshaft Clavicle Fractures.

PubMed

Ahrens, Philip M; Garlick, Nicholas I; Barber, Julie; Tims, Emily M

2017-08-16

The treatment of displaced midshaft clavicle fractures remains controversial. We undertook a multicenter randomized controlled trial to compare effectiveness and safety between nonoperative management and ORIF (open reduction and internal fixation) for displaced midshaft clavicle fractures in adults. Three hundred and one eligible adult patients were randomized to 1 of the 2 treatment groups and followed at 6 weeks, 3 months, and 9 months after recruitment. The primary outcome was the rate of radiographically evident nonunion at 3 months following treatment. Secondary outcomes were the rate of radiographically evident nonunion at 9 months, limb function measured using the Constant-Murley Score and DASH (Disabilities of the Arm, Shoulder and Hand) score, and patient satisfaction. There was no difference in the proportion of patients with radiographic evidence of nonunion at 3 months between the operative (28%) and nonoperative (27%) groups, whereas at 9 months the proportion with nonunion was significantly lower (p < 0.001) in the operative group (0.8%) than in the nonoperative group (11%). The DASH and Constant-Murley scores and patient satisfaction were all significantly better in the operative group than in the nonoperative group at 6 weeks and 3 months. Although at 3 months there was no evidence that surgery had reduced the rate of nonunion of displaced midshaft clavicle fractures, at 9 months nonoperative treatment had led to a significantly higher nonunion rate (11% compared with <1%). The rate of secondary surgical intervention during the trial period was 12 (11%) of the 147 patients in the nonoperative group. ORIF is a safe and reliable intervention with superior early functional outcomes and should be considered for patients who sustain this common injury. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Where’s the Noise? Key Features of Spontaneous Activity and Neural Variability Arise through Learning in a Deterministic Network

PubMed Central

Hartmann, Christoph; Lazar, Andreea; Nessler, Bernhard; Triesch, Jochen

2015-01-01

Even in the absence of sensory stimulation the brain is spontaneously active. This background “noise” seems to be the dominant cause of the notoriously high trial-to-trial variability of neural recordings. Recent experimental observations have extended our knowledge of trial-to-trial variability and spontaneous activity in several directions: 1. Trial-to-trial variability systematically decreases following the onset of a sensory stimulus or the start of a motor act. 2. Spontaneous activity states in sensory cortex outline the region of evoked sensory responses. 3. Across development, spontaneous activity aligns itself with typical evoked activity patterns. 4. The spontaneous brain activity prior to the presentation of an ambiguous stimulus predicts how the stimulus will be interpreted. At present it is unclear how these observations relate to each other and how they arise in cortical circuits. Here we demonstrate that all of these phenomena can be accounted for by a deterministic self-organizing recurrent neural network model (SORN), which learns a predictive model of its sensory environment. The SORN comprises recurrently coupled populations of excitatory and inhibitory threshold units and learns via a combination of spike-timing dependent plasticity (STDP) and homeostatic plasticity mechanisms. Similar to balanced network architectures, units in the network show irregular activity and variable responses to inputs. Additionally, however, the SORN exhibits sequence learning abilities matching recent findings from visual cortex and the network’s spontaneous activity reproduces the experimental findings mentioned above. Intriguingly, the network’s behaviour is reminiscent of sampling-based probabilistic inference, suggesting that correlates of sampling-based inference can develop from the interaction of STDP and homeostasis in deterministic networks. We conclude that key observations on spontaneous brain activity and the variability of neural responses can be accounted for by a simple deterministic recurrent neural network which learns a predictive model of its sensory environment via a combination of generic neural plasticity mechanisms. PMID:26714277

Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network.

PubMed

Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi

2016-07-11

Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to an improvement of neuromuscular disease treatment in Japan.

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC).

PubMed

Padberg, Frank; Kumpf, Ulrike; Mansmann, Ulrich; Palm, Ulrich; Plewnia, Christian; Langguth, Berthold; Zwanzger, Peter; Fallgatter, Andreas; Nolden, Jana; Burger, Max; Keeser, Daniel; Rupprecht, Rainer; Falkai, Peter; Hasan, Alkomiet; Egert, Silvia; Bajbouj, Malek

2017-12-01

Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs. ClinicalTrials.gov Identifier NCT0253016.

Recruitment of participants to a multiple sclerosis trial: The CombiRx experience

PubMed Central

Bhanushali, Minal J; Gustafson, Tarah; Powell, Steve; Conwit, Robin A; Wolinsky, Jerry S; Cutter, Gary R; Lublin, Fred; Cofield, Stacey S

2014-01-01

Background and Purpose: Participant recruitment is central to all clinical trials. Any delay in recruitment affects the completion and ultimate success of the trial. We report our experience with patient screening and randomization in CombiRx, which may inform the design of other trials. CombiRx was a multi-center, phase III, double-blind, randomized clinical trial comparing the combined use of interferon beta-1a and glatiramer acetate to either agent alone in patients with relapsing-remitting multiple sclerosis (RRMS). This trial was launched in January 2005 in 69 centers in the U.S. and Canada under a co-operative agreement with the National Institute of Neurological Disorders and Stroke (NINDS). The goal was to recruit 1000 patients over 1.5 years after a 6 month startup period. Instead, the investigators required 4.25 years to enroll 1008 patients. Methods: During this trial, we assessed the effectiveness of various recruitment strategies, utility of rescreening prior screen failures, and potential factors and strategies used in study conduct, research and infrastructure, all of which affected recruitment of participants and ultimately time to completion of CombiRx. We particularly were interested in the variability in time to site initiation between academic centers and private practice sites. Results: Physicians who were directly involved in the medical care of patients with RRMS were the primary source of patients recruited to CombiRx. A flexible study design that allowed for re-screening of the initial screen failures after a period of time was useful due to the relapsing/remitting course of the disease. Academic centers took longer to implement the trial than the private practice centers, but once sites were approved for enrollment, there was no important difference in the number of participants enrolled. Limitations: The CombiRx trial was conducted during a period when multiple new medications were being tested, thus affecting the pace of recruitment and limiting ability to generalize our experiences. However, the lessons we learned about process are relevant. Conclusion: Participants can be enrolled successfully in a clinical trial for RRMS, but factors affecting the time to achieve the requirements needed to start screening can be unpredictable and problematic. Prospective planning by the sponsors and investigators, use of central IRBs, master trial agreements and secure remote desktop access to the trial database may expedite trial implementation and participant recruitment. A good scientific research question with flexible study design and active involvement of the clinicians are important factors driving recruitment. Clinical trials can be implemented successfully both in private practices and at academic centers, a consideration when selecting sites. PMID:24686106

Patient reported outcomes (PROs) in clinical trials: is 'in-trial' guidance lacking? a systematic review.

PubMed

Kyte, Derek G; Draper, Heather; Ives, Jonathan; Liles, Clive; Gheorghe, Adrian; Calvert, Melanie

2013-01-01

Patient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on 'in-trial' activity (recruitment, data collection and data inputting) and the management of 'concerning' PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this review was to determine the extent and nature of published guidelines addressing these areas. Systematic review of 1,362 articles identified 18 eligible papers containing 'in-trial' guidelines. Two independent authors undertook a qualitative content analysis of the selected papers. Guidelines presented in each of the articles were coded according to an a priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86-0.97), and validity (<2% residual category coding). The majority of guidelines present were concerned with 'pre-trial' activities (72%), for example, outcome measure selection and study design issues, or 'post-trial' activities (16%) such as data analysis, reporting and interpretation. 'In-trial' guidelines represented 9.2% of all guidance across the papers reviewed, with content primarily focused on compliance, quality control, proxy assessment and reporting of data collection. There were no guidelines surrounding the management of concerning PRO data. The findings highlight there are minimal in-trial guidelines in publication regarding PRO data collection and management in clinical trials. No guidance appears to exist for researchers involved with the handling of concerning PRO data. Guidelines are needed, which support researchers to manage all PRO data appropriately and which facilitate unbiased data collection.

A Cochrane Systematic Review finds no significant difference in outcome or risk of postoperative complications between day care and in-patient cataract surgery.

PubMed

Fedorowicz, Zbigniew; Lawrence, David J; Gutierrez, Peter

2006-09-01

This review was conducted to determine reliable evidence regarding the safety, feasibility, effectiveness, and cost-effectiveness of cataract extraction performed as a day care versus in-patient procedure. The search to identify randomized controlled trials comparing day care and in-patient surgery for age-related cataract included the Cochrane Eyes and Vision Group Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS Latin American and Caribbean Literature on Health Sciences. Assessment of methodological quality was based on criteria defined by the Cochrane Collaboration. The primary outcome was the achievement of a satisfactory visual acuity 6 weeks after operation. Two trials, involving a total of 1284 people, are included. One trial reported statistically significant differences in early postoperative complication rates in the day care group, which had no clinical relevance to visual outcomes 4 months postoperatively. Mean change in visual acuity Snellen lines of the operated eye 4 months postoperatively was 4.1 standard deviation SD 2.3 for the day care group and 4.1 SD 2.2 for the in-patient group. Costs were 20% more for the in-patient group attributable to higher costs for overnight stay.

Efficacy and Mediation of a Theory-Based Physical Activity Intervention for African American Men Who Have Sex with Men: A Randomized Controlled Trial.

PubMed

Zhang, Jingwen; Jemmott, John B; O'Leary, Ann; Stevens, Robin; Jemmott, Loretta Sweet; Icard, Larry D; Hsu, Janet; Rutledge, Scott E

2017-02-01

Few trials have tested physical-activity interventions among sexual minorities, including African American men who have sex with men (MSM). We examined the efficacy and mediation of the Being Responsible for Ourselves (BRO) physical-activity intervention among African American MSM. African American MSM were randomized to the physical-activity intervention consisting of three 90-min one-on-one sessions or an attention-matched control intervention and completed pre-intervention, immediately post-intervention, and 6- and 12-month post-intervention audio computer-based surveys. Of the 595 participants, 503 completed the 12-month follow-up. Generalized estimating equation models revealed that the intervention increased self-reported physical activity compared with the control intervention, adjusted for pre-intervention physical activity. Mediation analyses suggested that the intervention increased reasoned action approach variables, subjective norm and self-efficacy, increasing intention immediately post-intervention, which increased physical activity during the follow-up period. Interventions targeting reasoned action approach variables may contribute to efforts to increase African American MSM's physical activity. The trial was registered with the ClinicalTrials.gov Identifier NCT02561286 .

A decade of the Clinical Trials Transformation Initiative: What have we accomplished? What have we learned?

PubMed

Tenaerts, P; Madre, L; Landray, M

2018-02-01

The Clinical Trials Transformation Initiative reflects on 10 years of working to improve the quality and efficiency of clinical trials. This article highlights many of the Clinical Trials Transformation Initiative's accomplishments and offers examples of the impact that the Clinical Trials Transformation Initiative has had on the clinical trials enterprise. After conducting more than 25 projects and issuing recommendations for specific strategies to improve the design and execution of clinical trials, some common themes and lessons learned have emerged. Lessons include the importance of engaging many stakeholders, advanced planning to address critical issues, discontinuation of non-value added practices, and new opportunities presented by technology. Through its work, the Clinical Trials Transformation Initiative has also derived some operational best practices for conducting collaborative, multi-stakeholder projects covering project selection, project team dynamics and execution, and multi-stakeholder meetings and team discussions. Through these initiatives, the Clinical Trials Transformation Initiative has helped move the needle toward needed change in the clinical trials enterprise that has directly impacted stakeholders and patients alike.

Ethics in clinical drug trial research in private practice.

PubMed

Beran, R G; Beran, M E

2006-09-01

Private clinics and clinicians have been involved in clinical drug trials for approximately two decades. This paper reviews the ethical consideration inherent in this process. Involvement of a single community based, private, Australian neurological clinic in the conduct of trials was audited. Changes in ethical considerations were analysed. The clinic previously audited its clinical trial involvement, starting with pharmaceutical company orchestrated trials. These were vetted by hospital based ethics committees (ECs) which then refused to review private research. A private EC accommodating NH & MRC standards was formed to assess private research. Indemnity concerns forced return to institutional ECs with government guaranteed indemnification. Trials evolved to investigator initiated, company sponsored studies thence a company asking the clinic to devise, sponsor and manage a trial. The latter relegated trial co-ordination to the clinic which would control publication thereby creating new ethical standards. Private practice trial involvement evolved from reluctant inclusion to a pivotal role in privately sponsored studies. Access to ECs is government endorsed and publication is independent for investigator-sponsored trials. There has been modification of standard operating procedures and enhanced ethical standards.

A Bayesian paradigm for decision-making in proof-of-concept trials.

PubMed

Pulkstenis, Erik; Patra, Kaushik; Zhang, Jianliang

2017-01-01

Decision-making is central to every phase of drug development, and especially at the proof of concept stage where risk and evidence must be weighed carefully, often in the presence of significant uncertainty. The decision to proceed or not to large expensive Phase 3 trials has significant implications to both patients and sponsors alike. Recent experience has shown that Phase 3 failure rates remain high. We present a flexible Bayesian quantitative decision-making paradigm that evaluates evidence relative to achieving a multilevel target product profile. A framework for operating characteristics is provided that allows the drug developer to design a proof-of-concept trial in light of its ability to support decision-making rather than merely achieve statistical significance. Operating characteristics are shown to be superior to traditional p-value-based methods. In addition, discussion related to sample size considerations, application to interim futility analysis and incorporation of prior historical information is evaluated.

User-driven health care: answering multidimensional information needs in individual patients utilizing post-EBM approaches: an operational model.

PubMed

Biswas, Rakesh; Maniam, Jayanthy; Lee, Edwin Wen Huo; Gopal, Premalatha; Umakanth, Shashikiran; Dahiya, Sumit; Ahmed, Sayeed

2008-10-01

The hypothesis in the conceptual model was that a user-driven innovation in presently available information and communication technology infrastructure would be able to meet patient and health professional users information needs and help them attain better health outcomes. An operational model was created to plan a trial on a sample diabetic population utilizing a randomized control trial design, assigning one randomly selected group of diabetics to receive electronic information intervention and analyse if it would improve their health outcomes in comparison with a matched diabetic population who would only receive regular medical intervention. Diabetes was chosen for this particular trial, as it is a major chronic illness in Malaysia as elsewhere in the world. It is in essence a position paper for how the study concept should be organized to stimulate wider discussion prior to beginning the study.

Update on simulation-based surgical training and assessment in ophthalmology: a systematic review.

PubMed

Thomsen, Ann Sofia S; Subhi, Yousif; Kiilgaard, Jens Folke; la Cour, Morten; Konge, Lars

2015-06-01

This study reviews the evidence behind simulation-based surgical training of ophthalmologists to determine (1) the validity of the reported models and (2) the ability to transfer skills to the operating room. Simulation-based training is established widely within ophthalmology, although it often lacks a scientific basis for implementation. We conducted a systematic review of trials involving simulation-based training or assessment of ophthalmic surgical skills among health professionals. The search included 5 databases (PubMed, EMBASE, PsycINFO, Cochrane Library, and Web of Science) and was completed on March 1, 2014. Overall, the included trials were divided into animal, cadaver, inanimate, and virtual-reality models. Risk of bias was assessed using the Cochrane Collaboration's tool. Validity evidence was evaluated using a modern validity framework (Messick's). We screened 1368 reports for eligibility and included 118 trials. The most common surgery simulated was cataract surgery. Most validity trials investigated only 1 or 2 of 5 sources of validity (87%). Only 2 trials (48 participants) investigated transfer of skills to the operating room; 4 trials (65 participants) evaluated the effect of simulation-based training on patient-related outcomes. Because of heterogeneity of the studies, it was not possible to conduct a quantitative analysis. The methodologic rigor of trials investigating simulation-based surgical training in ophthalmology is inadequate. To ensure effective implementation of training models, evidence-based knowledge of validity and efficacy is needed. We provide a useful tool for implementation and evaluation of research in simulation-based training. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Risk based monitoring (RBM) tools for clinical trials: A systematic review.

PubMed

Hurley, Caroline; Shiely, Frances; Power, Jessica; Clarke, Mike; Eustace, Joseph A; Flanagan, Evelyn; Kearney, Patricia M

2016-11-01

In November 2016, the Integrated Addendum to ICH-GCP E6 (R2) will advise trial sponsors to develop a risk-based approach to clinical trial monitoring. This new process is commonly known as risk based monitoring (RBM). To date, a variety of tools have been developed to guide RBM. However, a gold standard approach does not exist. This review aims to identify and examine RBM tools. Review of published and grey literature using a detailed search-strategy and cross-checking of reference lists. This review included academic and commercial instruments that met the Organisation for Economic Co-operation and Development (OECD) classification of RBM tools. Ninety-one potential RBM tools were identified and 24 were eligible for inclusion. These tools were published between 2000 and 2015. Eight tools were paper based or electronic questionnaires and 16 operated as Service as a System (SaaS). Risk associated with the investigational medicinal product (IMP), phase of the clinical trial and study population were examined by all tools and suitable mitigation guidance through on-site and centralised monitoring was provided. RBM tools for clinical trials are relatively new, their features and use varies widely and they continue to evolve. This makes it difficult to identify the "best" RBM technique or tool. For example, equivalence testing is required to determine if RBM strategies directed by paper based and SaaS based RBM tools are comparable. Such research could be embedded within multi-centre clinical trials and conducted as a SWAT (Study within a Trial). Copyright © 2016 Elsevier Inc. All rights reserved.

On-field investigation and process modelling of end-of-life vehicles treatment in the context of Italian craft-type authorized treatment facilities.

PubMed

Berzi, Lorenzo; Delogu, Massimo; Giorgetti, Alessandro; Pierini, Marco

2013-04-01

The present article analyses the current situation of End-of-Life-of-Vehicles (ELVs) management in Europe, with particular attention on Italian condition. Similarly to other European countries, metal recycling is the main activity of the whole system, but such situation is evolving due to the 2000/53/EC Directive, which sets out targets for Reuse, Recycling and Recovery of ELVs. Due to the relevance of the ELVs problem, in 2008 Italian Ministry of Environment subscribed a framework agreement with competent stakeholders as carmakers, dismantlers, shredders. The main result is an industrial plan to promote (amongst other objectives) technological progress for residual waste (Automotive Shredder Residue-ASR) treatment. According with Italian Trial 2006 analysis about ELVs, Reuse and Recycling rate is currently estimated to be about 81%. At the present time, dismantling plants constitute the first collection points for ELVs; for this reason, during 2009 an investigation has been done over a number of ten Authorized Treatment Facilities (ATFs) operating in Italy. The first step of the analysis was aimed to find out major practices and methods through observations of ATFs activities and interviews to operators. Furthermore, the depollution and dismantling treatments of about 70 different ELVs have been observed and timed in detail over a period of three months. The results included the identification of most relevant critical issues in ELVs treatment, such as distortions between scrapping activities and Directive's regulation, and the assessment of the time and of the resources needed to perform each operation. In the second step of the survey, a process simulation model has been built on the basis of such data. The model was aimed to include the real variability and all the uncertainties that are typical of dismantling activities; it is intended as a tool for process layout planning and for its management. Some control parameters have been introduced; these are able to dynamically modify process path depending on ELVs queues and priorities. The model can also be used for the economic assessments of single operations or of the whole treatment activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Individual differences in sensitivity to reward and punishment and neural activity during reward and avoidance learning

PubMed Central

Yoon, HeungSik; Kim, Hackjin; Hamann, Stephan

2015-01-01

In this functional neuroimaging study, we investigated neural activations during the process of learning to gain monetary rewards and to avoid monetary loss, and how these activations are modulated by individual differences in reward and punishment sensitivity. Healthy young volunteers performed a reinforcement learning task where they chose one of two fractal stimuli associated with monetary gain (reward trials) or avoidance of monetary loss (avoidance trials). Trait sensitivity to reward and punishment was assessed using the behavioral inhibition/activation scales (BIS/BAS). Functional neuroimaging results showed activation of the striatum during the anticipation and reception periods of reward trials. During avoidance trials, activation of the dorsal striatum and prefrontal regions was found. As expected, individual differences in reward sensitivity were positively associated with activation in the left and right ventral striatum during reward reception. Individual differences in sensitivity to punishment were negatively associated with activation in the left dorsal striatum during avoidance anticipation and also with activation in the right lateral orbitofrontal cortex during receiving monetary loss. These results suggest that learning to attain reward and learning to avoid loss are dependent on separable sets of neural regions whose activity is modulated by trait sensitivity to reward or punishment. PMID:25680989

Active video games: the mediating effect of aerobic fitness on body composition

PubMed Central

2012-01-01

Background Increased understanding of why and how physical activity impacts on health outcomes is needed to increase the effectiveness of physical activity interventions. A recent randomized controlled trial of an active video game (PlayStation EyeToy™) intervention showed a statistically significant treatment effect on the primary outcome, change from baseline in body mass index (BMI), which favored the intervention group at 24 weeks. In this short paper we evaluate the mediating effects of the secondary outcomes. Objective To identify mediators of the effect of an active video games intervention on body composition. Methods Data from a two-arm parallel randomized controlled trial of an active video game intervention (n = 322) were analyzed. The primary outcome was change from baseline in BMI. A priori secondary outcomes were considered as potential mediators of the intervention on BMI, including aerobic fitness (VO2Max), time spent in moderate-to-vigorous physical activity (MVPA), and food snacking at 24 weeks. Results Only aerobic fitness at 24 weeks met the conditions for mediation, and was a significant mediator of BMI. Conclusion Playing active video games can have a positive effect on body composition in overweight or obese children and this effect is most likely mediated through improved aerobic fitness. Future trials should examine other potential mediators related to this type of intervention. Trial registration Australian New Zealand Clinical Trials Registry Website: http://www.anzctr.org.au Study ID number: ACTRN12607000632493 PMID:22554052

Trial-Based Functional Analysis Informs Treatment for Vocal Scripting.

PubMed

Rispoli, Mandy; Brodhead, Matthew; Wolfe, Katie; Gregori, Emily

2018-05-01

Research on trial-based functional analysis has primarily focused on socially maintained challenging behaviors. However, procedural modifications may be necessary to clarify ambiguous assessment results. The purposes of this study were to evaluate the utility of iterative modifications to trial-based functional analysis on the identification of putative reinforcement and subsequent treatment for vocal scripting. For all participants, modifications to the trial-based functional analysis identified a primary function of automatic reinforcement. The structure of the trial-based format led to identification of social attention as an abolishing operation for vocal scripting. A noncontingent attention treatment was evaluated using withdrawal designs for each participant. This noncontingent attention treatment resulted in near zero levels of vocal scripting for all participants. Implications for research and practice are presented.

Evaluation of imidacloprid-treated traps as an attract and kill system for filth flies during contingency operations.

PubMed

Dunford, James C; Hoel, David F; Hertz, Jeffrey C; England, David B; Dunford, Kelly R; Stoops, Craig A; Szumlas, Daniel E; Hogsette, Jerome A

2013-01-01

Two field trials were conducted to evaluate if filth fly trap efficacy was increased by augmentation with an insecticide application to the trap's exterior. Four Fly Terminator Pro traps (Farnam Companies, Inc, Phoenix, AZ) baited with Terminator Fly Attractant (in water) were suspended on polyvinyl chloride pipe framing at a municipal waste transfer site in Clay County, Florida. The outer surfaces of 2 traps were treated with Maxforce Fly Spot Bait (Bayer Environmental Science, Research Triangle Park, NC) (10% imidacloprid) to compare kill rates between treated and untreated traps. Kill consisted of total flies collected from inside traps and from mesh nets suspended beneath all traps, both treated and untreated. Each of 2 treated and untreated traps was rotated through 4 trap sites every 24 hrs. In order to evaluate operational utility and conservation of supplies during remote contingency operations, fly attractant remained in traps for the duration of the first trial but was changed daily during the second trial (following manufacturer's recommendations). In addition, ½ strength Terminator Fly Attractant was used during the first trial and traps were set at full strength during the second trial. Flies collected within the traps and in mesh netting were counted and identified. Three species, Musca domestica (L.), Chrysomya megacephala (F.), and Lucilia cuprina (Wiedemann), comprised the majority of samples in both trials. The net samples recovered more flies when the outer surface was treated with imidacloprid, however, treated traps collected fewer flies inside the trap than did untreated traps for both trials. No significant statistical advantage was found in treating Fly Terminator Pro trap exteriors with Maxforce Fly Spot Bait. However, reducing manufacturer's recommended strength of Terminator Fly Attractant showed similar results to traps set at full strength. Treating the outer surfaces may improve kill of fly species that do not enter the trap. Terminator Fly Attractant was also found to be more effective if traps were not changed daily and left to hold dead flies for longer periods.

Pre-Operative nutrition In Neck of femur Trial (POINT)--carbohydrate loading in patients with fragility hip fracture: study protocol for a randomised controlled trial.

PubMed

Moppett, Iain K; Greenhaff, Paul L; Ollivere, Ben J; Joachim, Theophillus; Lobo, Dileep N; Rowlands, Martin

2014-12-04

Trauma such as hip fracture initiates a neurohumoral stress response that changes the balance between anabolism and catabolism resulting in muscle breakdown and reduced mobilisation. Various studies have demonstrated a reduction in catabolism with pre-operative carbohydrate loading but only in an elective setting. This is a two-centre, randomised double-blinded trial in the United Kingdom. Sample size will be 30 patients (approximately 15 from each centre). Randomisation will be web based using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be >70 years of age, cognitively intact (Abbreviated Mental Score ≥ 7), able to give informed consent, and admitted directly through the emergency department with fractured neck of femur requiring hemiarthroplasty. Intervention will consist of two carbohydrate drinks (Nutricia pre-Op) given the night before, and the morning of the surgery. The control will receive two placebo drinks of equal volume. All participants will receive standard hospital care at the discretion of the clinical team. The primary outcome is the difference between groups in insulin resistance calculated by a glucose tolerance test administered pre-operatively and 24 hours postoperatively. Secondary endpoints will be changes in muscle carbohydrate metabolism (biopsy), mobility (Cumulative Ambulation Score) and subjective measures of tolerability. This is a small-scale pilot study, investigating the benefits and tolerability of carbohydrate loading in an emergency setting in a frail elderly group with known high morbidity and mortality. Positive findings will provide the basis for a larger scale study. Current Controlled Trials ISRCTN91109766 (7 April 2014); NRES ref: 13/EM/0214Trial Sponsor: University of Nottingham Ref.13036.

Sweat Chloride as A Biomarker of CFTR Activity: Proof of Concept and Ivacaftor Clinical Trial Data

PubMed Central

Accurso, Frank J.; Van Goor, Fredrick; Zha, Jiuhong; Stone, Anne J.; Dong, Qunming; Ordonez, Claudia L.; Rowe, Steven M.; Clancy, John Paul; Konstan, Michael W.; Hoch, Heather E.; Heltshe, Sonya L.; Ramsey, Bonnie W.; Campbell, Preston W.; Ashlock, Melissa A.

2014-01-01

Background We examined data from a Phase 2 trial {NCT00457821 } of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with a G551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity. Methods Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing, and analysis was employed for the first time.. Sweat chloride and chloride ion transport (NPD) were integrated into a model of CFTR activity. Results Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40% of normal. Conclusions Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators. PMID:24660233

Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data.

PubMed

Accurso, Frank J; Van Goor, Fredrick; Zha, Jiuhong; Stone, Anne J; Dong, Qunming; Ordonez, Claudia L; Rowe, Steven M; Clancy, John Paul; Konstan, Michael W; Hoch, Heather E; Heltshe, Sonya L; Ramsey, Bonnie W; Campbell, Preston W; Ashlock, Melissa A

2014-03-01

We examined data from a Phase 2 trial {NCT00457821} of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with aG551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity. Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing,and analysis was employed for the first time. Sweat chloride and chloride ion transport (NPD) were integrated into a model of CFTR activity. Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40% of normal. Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators.

Perioperative psychotherapy for persistent post-surgical pain and physical impairment: a meta-analysis of randomised trials.

PubMed

Wang, L; Chang, Y; Kennedy, S A; Hong, P J; Chow, N; Couban, R J; McCabe, R E; Bieling, P J; Busse, J W

2018-06-01

Persistent post-surgical pain affects 10-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent post-surgical pain and physical impairment. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Our search of five electronic databases, up to September 1, 2016, found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) -1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) -1.56 to -0.55 cm; risk difference (RD) for achieving no more than mild pain (≤3 cm) 14%, 95% CI 8-21%] and physical impairment [WMD -9.87% on the 0-100% Oswestry Disability Index, 95% CI -13.42 to -6.32%, RD for achieving no more than mild disability (≤20%) 21%, 95% CI 13-29%]. Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome. PROSPERO CRD42016047335. Copyright © 2017. Published by Elsevier Ltd.

Classification of single-trial auditory events using dry-wireless EEG during real and motion simulated flight.

PubMed

Callan, Daniel E; Durantin, Gautier; Terzibas, Cengiz

2015-01-01

Application of neuro-augmentation technology based on dry-wireless EEG may be considerably beneficial for aviation and space operations because of the inherent dangers involved. In this study we evaluate classification performance of perceptual events using a dry-wireless EEG system during motion platform based flight simulation and actual flight in an open cockpit biplane to determine if the system can be used in the presence of considerable environmental and physiological artifacts. A passive task involving 200 random auditory presentations of a chirp sound was used for evaluation. The advantage of this auditory task is that it does not interfere with the perceptual motor processes involved with piloting the plane. Classification was based on identifying the presentation of a chirp sound vs. silent periods. Evaluation of Independent component analysis (ICA) and Kalman filtering to enhance classification performance by extracting brain activity related to the auditory event from other non-task related brain activity and artifacts was assessed. The results of permutation testing revealed that single trial classification of presence or absence of an auditory event was significantly above chance for all conditions on a novel test set. The best performance could be achieved with both ICA and Kalman filtering relative to no processing: Platform Off (83.4% vs. 78.3%), Platform On (73.1% vs. 71.6%), Biplane Engine Off (81.1% vs. 77.4%), and Biplane Engine On (79.2% vs. 66.1%). This experiment demonstrates that dry-wireless EEG can be used in environments with considerable vibration, wind, acoustic noise, and physiological artifacts and achieve good single trial classification performance that is necessary for future successful application of neuro-augmentation technology based on brain-machine interfaces.

Pragmatic clinical trials: ethical imperatives and opportunities.

PubMed

Kalkman, Shona; van Thiel, Ghislaine J M W; Grobbee, Diederick E; van Delden, Johannes J M

2018-06-12

Pragmatic clinical trials generate robust real-world evidence that holds great potential to better inform decision making regarding new medicines. For clinicians, patients and regulators, this evidence would preferably be available sooner rather than later. This means that, ideally, market authorization of any given medicine is accompanied by evidence obtained from a pragmatic trial. Given the operational and regulatory complexities of pragmatic trials in general, stakeholders tend to be hesitant to employ more pragmatism at the time of market approval. One prominent hurdle for the conduct of pragmatic trials is the concern that pragmatic design features conflict with ethical standards for clinical trials. To encourage timely yet responsible generation of real-world evidence through clinical trials, it is important to delineate exactly which areas, from a societal point of view, demand early pragmatic evaluations. We also urge stakeholders to recognize how the current system of trial ethics oversight already accommodates for more-pragmatic approaches, and how new ideas about their permissibility have progressed in the bioethics literature. Copyright © 2018. Published by Elsevier Ltd.

Development of dual field magnetic flux leakage (MFL) inspection technology to detect mechanical damage.

DOT National Transportation Integrated Search

2013-03-01

This report details the development and testing of a dual magnetization in-line inspection (ILI) : tool for detecting mechanical damage in operating pipelines, including the first field trials of a : fully operational dual-field magnetic flux leakage...

Final Report: Independent Design Review, Celanese Fiber Operations Superfund Site, Shelby, North Carolina, EPA Region 4

EPA Pesticide Factsheets

The Celanese site is located in Shelby, North Carolina. Operation of the P&T system was discontinued on a trial basis for two years to evaluate monitored natural attenuation as a potential ground water remedy.

Clinical trials: bringing research to the bedside.

PubMed

Arvay, C A

1991-02-01

Over the years, clinical trials with their structured treatment plans and multicenter involvement have been instrumental in developing new treatments and establishing standard of care therapy. While clinical trials strive to advance medical knowledge, they provide scientifically sound, state of the art care and their use should be increased. The Brain Tumor Cooperative Group, one such NCI-sponsored cooperative group, has been the primary group for the treatment of malignant gliomas. As the field of neuro-oncology expands, the neuroscience nurse needs to develop an understanding of clinical trials and their operation. The nurse is in an optimal position to support medical research and the research participant.

Feasibility and effects of patient-cooperative robot-aided gait training applied in a 4-week pilot trial

PubMed Central

2012-01-01

Background Functional training is becoming the state-of-the-art therapy approach for rehabilitation of individuals after stroke and spinal cord injury. Robot-aided treadmill training reduces personnel effort, especially when treating severely affected patients. Improving rehabilitation robots towards more patient-cooperative behavior may further increase the effects of robot-aided training. This pilot study aims at investigating the feasibility of applying patient-cooperative robot-aided gait rehabilitation to stroke and incomplete spinal cord injury during a therapy period of four weeks. Short-term effects within one training session as well as the effects of the training on walking function are evaluated. Methods Two individuals with chronic incomplete spinal cord injury and two with chronic stroke trained with the Lokomat gait rehabilitation robot which was operated in a new, patient-cooperative mode for a period of four weeks with four training sessions of 45 min per week. At baseline, after two and after four weeks, walking function was assessed with the ten meter walking test. Additionally, muscle activity of the major leg muscles, heart rate and the Borg scale were measured under different walking conditions including a non-cooperative position control mode to investigate the short-term effects of patient-cooperative versus non-cooperative robot-aided gait training. Results Patient-cooperative robot-aided gait training was tolerated well by all subjects and performed without difficulties. The subjects trained more actively and with more physiological muscle activity than in a non-cooperative position-control mode. One subject showed a significant and relevant increase of gait speed after the therapy, the three remaining subjects did not show significant changes. Conclusions Patient-cooperative robot-aided gait training is feasible in clinical practice and overcomes the main points of criticism against robot-aided gait training: It enables patients to train in an active, variable and more natural way. The limited number of subjects in this pilot trial does not permit valid conclusions on the effect of patient-cooperative robot-aided gait training on walking function. A large, possibly multi-center randomized controlled clinical trial is required to shed more light on this question. PMID:22650320

Effect of a 24-month physical activity intervention vs health education on cognitive outcomes in sedentary older adults: the LIFE randomized trial

USDA-ARS?s Scientific Manuscript database

Importance: Epidemiologic evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed. Objective: To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) o...

Health Activities Project (HAP), Trial Edition III.

ERIC Educational Resources Information Center

Buller, Dave; And Others

Contained within this Health Activities Project (HAP) trial edition (set III) are a teacher information folio and numerous student activity folios which center around the idea that students in grades 5-8 can control their own health and safety. Each student folio is organized into an Overview, Health Background, Materials, Setting Up, and…

Health Activities Project (HAP), Trial Edition II.

ERIC Educational Resources Information Center

Buller, Dave; And Others

Contained within this Health Activities Project (HAP) trial edition (set II) are a teacher information folio and numerous student activity folios which center around the idea that students in grades 5-8 can control their own health and safety. Each student folio is organized into a Synopsis, Health Background, Materials, Setting Up, and Activities…