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  1. Molecular-state close-coupling theory including continuum states. I. Derivation of close-coupled equations

    International Nuclear Information System (INIS)

    Thorson, W.R.; Bandarage, G.

    1988-01-01

    We formulate a close-coupling theory of slow ion-atom collisions based on molecular (adiabatic) electronic states, and including the electronic continuum. The continuum is represented by packet states spanning it locally and constructed explicitly from exact continuum states. Particular attention is given to two fundamental questions: (1) Unbound electrons can escape from the local region spanned by the packet states. We derive close-coupled integral equations correctly including the escape effects; the ''propagator'' generated by these integral equations does not conserve probability within the close-coupled basis. Previous molecular-state formulations including the continuum give no account of escape effects. (2) Nonadiabatic couplings of adiabatic continuum states with the same energy are singular, reflecting the fact that an adiabatic description of continuum behavior is not valid outside a local region. We treat these singularities explicitly and show that an accurate representation of nonadiabatic couplings within the local region spanned by a set of packet states is well behaved. Hence an adiabatic basis-set description can be used to describe close coupling to the continuum in a local ''interaction region,'' provided the effects of escape are included. In principle, the formulation developed here can be extended to a large class of model problems involving many-electron systems and including models for Penning ionization and collisional detachment processes

  2. Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database.

    Science.gov (United States)

    Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina

    2016-03-22

    To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future.

  3. Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database

    International Nuclear Information System (INIS)

    Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M.; Lössl, Kristina

    2016-01-01

    To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future. The online version of this article (doi:10.1186/s13014-016-0624-8) contains supplementary material, which is available to authorized users

  4. Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial.

    Science.gov (United States)

    Morris, Jonathan M; Roberts, Christine L; Bowen, Jennifer R; Patterson, Jillian A; Bond, Diana M; Algert, Charles S; Thornton, Jim G; Crowther, Caroline A

    2016-01-30

    Preterm pre-labour ruptured membranes close to term is associated with increased risk of neonatal infection, but immediate delivery is associated with risks of prematurity. The balance of risks is unclear. We aimed to establish whether immediate birth in singleton pregnancies with ruptured membranes close to term reduces neonatal infection without increasing other morbidity. The PPROMT trial was a multicentre randomised controlled trial done at 65 centres across 11 countries. Women aged over 16 years with singleton pregnancies and ruptured membranes before the onset of labour between 34 weeks and 36 weeks and 6 days weeks who had no signs of infection were included. Women were randomly assigned (1:1) by a computer-generated randomisation schedule with variable block sizes, stratified by centre, to immediate delivery or expectant management. The primary outcome was the incidence of neonatal sepsis. Secondary infant outcomes included a composite neonatal morbidity and mortality indicator (ie, sepsis, mechanical ventilation ≥24 h, stillbirth, or neonatal death); respiratory distress syndrome; any mechanical ventilation; and duration of stay in a neonatal intensive or special care unit. Secondary maternal outcomes included antepartum or intrapartum haemorrhage, intrapartum fever, postpartum treatment with antibiotics, and mode of delivery. Women and caregivers could not be masked, but those adjudicating on the primary outcome were masked to group allocation. Analyses were by intention to treat. This trial is registered with the International Clinical Trials Registry, number ISRCTN44485060. Between May 28, 2004, and June 30, 2013, 1839 women were recruited and randomly assigned: 924 to the immediate birth group and 915 to the expectant management group. One woman in the immediate birth group and three in the expectant group were excluded from the primary analyses. Neonatal sepsis occurred in 23 (2%) of 923 neonates whose mothers were assigned to immediate birth and 29

  5. Enhancing Efficiency of Safeguards at Facilities that are Shutdown or Closed-Down, including those being Decommissioned

    Energy Technology Data Exchange (ETDEWEB)

    Moran, B. [Brookhaven National Lab. (BNL), Upton, NY (United States); Stern, W. [Brookhaven National Lab. (BNL), Upton, NY (United States); Colley, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Marzo, M. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2016-12-15

    International Atomic Energy Agency (IAEA) safeguards involves verification activities at a wide range of facilities in a variety of operational phases (e.g., under construction, start-up, operating, shutdown, closed-down, and decommissioned). Safeguards optimization for each different facility type and operational phase is essential for the effectiveness of safeguards implementation. The IAEA’s current guidance regarding safeguards for the different facility types in the various lifecycle phases is provided in its Design Information Examination (DIE) and Verification (DIV) procedure. 1 Greater efficiency in safeguarding facilities that are shut down or closed down, including those being decommissioned, could allow the IAEA to use a greater portion of its effort to conduct other verification activities. Consequently, the National Nuclear Security Administration’s Office of International Nuclear Safeguards sponsored this study to evaluate whether there is an opportunity to optimize safeguards approaches for facilities that are shutdown or closed-down. The purpose of this paper is to examine existing safeguards approaches for shutdown and closed-down facilities, including facilities being decommissioned, and to seek to identify whether they may be optimized.

  6. The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial.

    Science.gov (United States)

    Neubert, Antje; Baarslag, Manuel Alberto; Dijk, Monique van; Rosmalen, Joost van; Standing, Joseph F; Sheng, Yucheng; Rascher, Wolfgang; Roberts, Deborah; Winslade, Jackie; Rawcliffe, Louise; Hanning, Sara M; Metsvaht, Tuuli; Giannuzzi, Viviana; Larsson, Peter; Pokorná, Pavla; Simonetti, Alessandra; Tibboel, Dick

    2017-06-21

    Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2-18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Contemporary Aspects of Marketing in Clinical Trials Including Segments of IT and Technology Transfer

    Science.gov (United States)

    Stamenovic, Milorad; Dobraca, Amra; Smajlovic, Mersiha

    2018-01-01

    Introduction: The aim of this paper is to present the marketing strategy and the application of management (marketing management) and advertising in order to increase the efficiency of innovative approach in clinical trials that include and involve the use of new technologies and transfer of technologies. Material and Methods: This paper has a descriptive character and represents a narrative review of the literature and new model implementation. Results: Marketing models are primarily used to improve the inclusion of a larger (and appropriate) number of patients, but they can be credited for the stay and monitoring of patients in the trial. Regulatory mechanisms play an important role in the application of various marketing strategies within clinical trials. The value for the patient as the most important stakeholder is defined in the field of clinical trials according to Kotler’s value model for the consumer. Conclusion: In order to achieve the best results it is important to adequately examine all the elements of clinical trials and apply this knowledge in creation of a marketing plan that will be made in accordance with the legal regulations defined globally and locally. In this paper, two challenges have been highlighted for the adequate application of marketing tools in the field of clinical trials, namely: defining business elements in order to provide an adequate marketing approach for clinical trials and technology transfer and ensuring uniformity and regulatory affirmation of marketing attitudes in clinical trials in all regions in which they are carried out in accordance with ICH-GCP and valid regulations. PMID:29719318

  8. Contemporary Aspects of Marketing in Clinical Trials Including Segments of IT and Technology Transfer.

    Science.gov (United States)

    Stamenovic, Milorad; Dobraca, Amra; Smajlovic, Mersiha

    2018-01-01

    The aim of this paper is to present the marketing strategy and the application of management (marketing management) and advertising in order to increase the efficiency of innovative approach in clinical trials that include and involve the use of new technologies and transfer of technologies. This paper has a descriptive character and represents a narrative review of the literature and new model implementation. Marketing models are primarily used to improve the inclusion of a larger (and appropriate) number of patients, but they can be credited for the stay and monitoring of patients in the trial. Regulatory mechanisms play an important role in the application of various marketing strategies within clinical trials. The value for the patient as the most important stakeholder is defined in the field of clinical trials according to Kotler's value model for the consumer. In order to achieve the best results it is important to adequately examine all the elements of clinical trials and apply this knowledge in creation of a marketing plan that will be made in accordance with the legal regulations defined globally and locally. In this paper, two challenges have been highlighted for the adequate application of marketing tools in the field of clinical trials, namely: defining business elements in order to provide an adequate marketing approach for clinical trials and technology transfer and ensuring uniformity and regulatory affirmation of marketing attitudes in clinical trials in all regions in which they are carried out in accordance with ICH-GCP and valid regulations.

  9. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial

    NARCIS (Netherlands)

    Moet, F. Johannes; Pahan, David; Oskam, Linda; Richardus, Jan H.; van Brakel, Wim H.; Klatser, Paul R.; Saunderson, Paul R.; Smith, W. Cairns S.; Withington, Steve G.; Richardus, Jan Hendrik; Schuring, Ron P.; Faber, Roel; Borsboom, Gerard J. J. M.

    2008-01-01

    OBJECTIVE: To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. DESIGN: Single centre, double blind, cluster randomised, placebo controlled trial. SETTING: Leprosy control programme in two districts of northwest Bangladesh with a

  10. Should desperate volunteers be included in randomised controlled trials?

    Science.gov (United States)

    Allmark, P; Mason, S

    2006-09-01

    Randomised controlled trials (RCTs) sometimes recruit participants who are desperate to receive the experimental treatment. This paper defends the practice against three arguments that suggest it is unethical first, desperate volunteers are not in equipoise. Second clinicians, entering patients onto trials are disavowing their therapeutic obligation to deliver the best treatment; they are following trial protocols rather than delivering individualised care. Research is not treatment; its ethical justification is different. Consent is crucial. Third, desperate volunteers do not give proper consent: effectively, they are coerced. This paper responds by advocating a notion of equipoise based on expert knowledge and widely shared values. Where such collective, expert equipoise exists there is a prima facie case for an RCT. Next the paper argues that trial entry does not involve clinicians disavowing their therapeutic obligation; individualised care based on insufficient evidence is not in patients best interest. Finally, it argues that where equipoise exists it is acceptable to limit access to experimental agents; desperate volunteers are not coerced because their desperation does not translate into a right to receive what they desire.

  11. Closed-form solutions for linear regulator-design of mechanical systems including optimal weighting matrix selection

    Science.gov (United States)

    Hanks, Brantley R.; Skelton, Robert E.

    1991-01-01

    This paper addresses the restriction of Linear Quadratic Regulator (LQR) solutions to the algebraic Riccati Equation to design spaces which can be implemented as passive structural members and/or dampers. A general closed-form solution to the optimal free-decay control problem is presented which is tailored for structural-mechanical systems. The solution includes, as subsets, special cases such as the Rayleigh Dissipation Function and total energy. Weighting matrix selection is a constrained choice among several parameters to obtain desired physical relationships. The closed-form solution is also applicable to active control design for systems where perfect, collocated actuator-sensor pairs exist. Some examples of simple spring mass systems are shown to illustrate key points.

  12. Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials.

    Science.gov (United States)

    Schroen, Anneke T; Petroni, Gina R; Wang, Hongkun; Gray, Robert; Wang, Xiaofei F; Cronin, Walter; Sargent, Daniel J; Benedetti, Jacqueline; Wickerham, Donald L; Djulbegovic, Benjamin; Slingluff, Craig L

    2010-08-01

    A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual. We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting. A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency. Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (accrual rate) were consistently closed due to insufficient accrual. This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success. Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining

  13. Milligan-Morgan (Open) Versus Ferguson Haemorrhoidectomy (Closed): A Systematic Review and Meta-Analysis of Published Randomized, Controlled Trials.

    Science.gov (United States)

    Bhatti, Muhammad I; Sajid, Muhammad Shafique; Baig, Mirza K

    2016-06-01

    The purpose of this article is to systematically analyse the randomized, controlled trials (RCTs) comparing Ferguson or closed haemorrhoidectomy (CH) versus open haemorrhoidectomy (OH) or Milligan-Morgan haemorrhoidectomy in the management of haemorrhoidal disease (HD). RCTs on the effectiveness of CH and OH in the management of HD were analysed systematically using RevMan(®), and combined outcome was expressed as odds ratio (OR) and standardized mean difference. Eleven CRTs encompassing 1326 patients were analysed systematically. There was significant heterogeneity among included trials. Therefore, in the random effects model, CH was associated with a reduced post-operative pain (SMD, -0.36; 95 % CI, -0.64, -0.07; z = 2.45; p = 0.01), faster wound healing (OR, 0.08; 95 % CI, 0.02, 0.24; z = 4.33; p SMD, 6.10; 95 % CI, 3.21, 8.98; z = 4.13; p SMD, -0.33; 95 % CI, -0.68, 0.03; z = 1.82; p = 0.07), length of hospital stay, post-operative complications, HD recurrence and risk of surgical site infection were similar in both groups. CH has clinically measurable advantages over OH in terms of reduced post-operative pain, lower risk of post-operative bleeding and faster wound healing.

  14. Explicitly-correlated ring-coupled-cluster-doubles theory: Including exchange for computations on closed-shell systems

    Energy Technology Data Exchange (ETDEWEB)

    Hehn, Anna-Sophia; Holzer, Christof; Klopper, Wim, E-mail: klopper@kit.edu

    2016-11-10

    Highlights: • Ring-coupled-cluster-doubles approach now implemented with exchange terms. • Ring-coupled-cluster-doubles approach now implemented with F12 functions. • Szabo–Ostlund scheme (SO2) implemented for use in SAPT. • Fast convergence to the limit of a complete basis. • Implementation in the TURBOMOLE program system. - Abstract: Random-phase-approximation (RPA) methods have proven to be powerful tools in electronic-structure theory, being non-empirical, computationally efficient and broadly applicable to a variety of molecular systems including small-gap systems, transition-metal compounds and dispersion-dominated complexes. Applications are however hindered due to the slow basis-set convergence of the electron-correlation energy with the one-electron basis. As a remedy, we present approximate explicitly-correlated RPA approaches based on the ring-coupled-cluster-doubles formulation including exchange contributions. Test calculations demonstrate that the basis-set convergence of correlation energies is drastically accelerated through the explicitly-correlated approach, reaching 99% of the basis-set limit with triple-zeta basis sets. When implemented in close analogy to early work by Szabo and Ostlund [36], the new explicitly-correlated ring-coupled-cluster-doubles approach including exchange has the perspective to become a valuable tool in the framework of symmetry-adapted perturbation theory (SAPT) for the computation of dispersion energies of molecular complexes of weakly interacting closed-shell systems.

  15. [The informed consent in international clinical trials including developing countries].

    Science.gov (United States)

    Montenegro Surís, Alexander; Monreal Agüero, Magda Elaine

    2008-01-01

    The informed consent procedure has been one of the most important controversies of ethical debates about clinical trials in developing countries. In this essay we present our recommendations about important aspects to consider in the informed consent procedure for clinical trials in developing countries. We performed a full publications review identified by MEDLINE using these terms combinations: informed consent, developing countries, less developed countries and clinical trials. To protect volunteers in less developed countries should be valuated the importance of the community in the informed consent proceeding. The signing and dating of the informed consent form is not always the best procedure to document the informed consent. The informed consent form should be written by local translators. Alternative medias of communications could be needed for communicatios of the information to volunteers. Comparing with developed countries the informed consent proceeding in clinical trials in developing countries frequently require additional efforts. The developing of pragmatic researches is needed to implement informed consent proceedings assuring subjects voluntarily in each developing country. The main aspects to define in each clinical trial for each country are the influence of the community, the effective communication of the information, the documentation of the informed consent and local authority's control.

  16. Clinical Trials

    Medline Plus

    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... care providers might be part of your treatment team. They will monitor your health closely. You may ...

  17. Comparison of cardiac output optimization with an automated closed-loop goal-directed fluid therapy versus non standardized manual fluid administration during elective abdominal surgery: first prospective randomized controlled trial.

    Science.gov (United States)

    Lilot, Marc; Bellon, Amandine; Gueugnon, Marine; Laplace, Marie-Christine; Baffeleuf, Bruno; Hacquard, Pauline; Barthomeuf, Felicie; Parent, Camille; Tran, Thomas; Soubirou, Jean-Luc; Robinson, Philip; Bouvet, Lionel; Vassal, Olivia; Lehot, Jean-Jacques; Piriou, Vincent

    2018-01-27

    An intraoperative automated closed-loop system for goal-directed fluid therapy has been successfully tested in silico, in vivo and in a clinical case-control matching. This trial compared intraoperative cardiac output (CO) in patients managed with this closed-loop system versus usual practice in an academic medical center. The closed-loop system was connected to a CO monitoring system and delivered automated colloid fluid boluses. Moderate to high-risk abdominal surgical patients were randomized either to the closed-loop or the manual group. Intraoperative final CO was the primary endpoint. Secondary endpoints were intraoperative overall mean cardiac index (CI), increase from initial to final CI, intraoperative fluid volume and postoperative outcomes. From January 2014 to November 2015, 46 patients were randomized. There was a lower initial CI (2.06 vs. 2.51 l min -1 m -2 , p = 0.042) in the closed-loop compared to the control group. No difference in final CO and in overall mean intraoperative CI was observed between groups. A significant relative increase from initial to final CI values was observed in the closed-loop but not the control group (+ 28.6%, p = 0.006 vs. + 1.2%, p = 0.843). No difference was found for intraoperative fluid management and postoperative outcomes between groups. There was no significant impact on the primary study endpoint, but this was found in a context of unexpected lower initial CI in the closed-loop group.Trial registry number ID-RCB/EudraCT: 2013-A00770-45. ClinicalTrials.gov Identifier NCT01950845, date of registration: 17 September 2013.

  18. Protocol for the immediate delivery versus expectant care of women with preterm prelabour rupture of the membranes close to term (PPROMT Trial [ISRCTN44485060

    Directory of Open Access Journals (Sweden)

    Buchanan Sarah L

    2006-03-01

    Full Text Available Abstract Background Preterm prelabour rupture of membranes (PPROM complicates up to 2% of all pregnancies and is the cause of 40% of all preterm births. The optimal management of women with PPROM prior to 37 weeks, is not known. Furthermore, diversity in current clinical practice suggests uncertainty about the appropriate clinical management. There are two options for managing PPROM, expectant management (a wait and see approach or early planned birth. Infection is the main risk for women in which management is expectant. This risk need to be balanced against the risk of iatrogenic prematurity if early delivery is planned. The different treatment options may also have different health care costs. Expectant management results in prolonged antenatal hospitalisation while planned early delivery may necessitate intensive care of the neonate for problems associated with prematurity. Methods/Design We aim to evaluate the effectiveness of early planned birth compared with expectant management for women with PPROM between 34 weeks and 366 weeks gestation, in a randomised controlled trial. A secondary aim is a cost analysis to establish the economic impact of the two treatment options and establish the treatment preferences of women with PPROM close to term. The early planned birth group will be delivered within 24 hours according to local management protocols. In the expectant management group birth will occur after spontaneous labour, at term or when the attending clinician feels that birth is indicated according to usual care. Approximately 1812 women with PPROM at 34–366 weeks gestation will be recruited for the trial. The primary outcome of the study is neonatal sepsis. Secondary infant outcomes include respiratory distress, perinatal mortality, neonatal intensive care unit admission, assisted ventilation and early infant development. Secondary maternal outcomes include chorioamnionitis, postpartum infection treated with antibiotics, antepartum

  19. Closed-form solutions for linear regulator design of mechanical systems including optimal weighting matrix selection

    Science.gov (United States)

    Hanks, Brantley R.; Skelton, Robert E.

    1991-01-01

    Vibration in modern structural and mechanical systems can be reduced in amplitude by increasing stiffness, redistributing stiffness and mass, and/or adding damping if design techniques are available to do so. Linear Quadratic Regulator (LQR) theory in modern multivariable control design, attacks the general dissipative elastic system design problem in a global formulation. The optimal design, however, allows electronic connections and phase relations which are not physically practical or possible in passive structural-mechanical devices. The restriction of LQR solutions (to the Algebraic Riccati Equation) to design spaces which can be implemented as passive structural members and/or dampers is addressed. A general closed-form solution to the optimal free-decay control problem is presented which is tailored for structural-mechanical system. The solution includes, as subsets, special cases such as the Rayleigh Dissipation Function and total energy. Weighting matrix selection is a constrained choice among several parameters to obtain desired physical relationships. The closed-form solution is also applicable to active control design for systems where perfect, collocated actuator-sensor pairs exist.

  20. Inverted duplication including Endothelin 3 closely related to dermal hyperpigmentation in Silkie chickens

    Directory of Open Access Journals (Sweden)

    Ming TIAN,Suyun FANG,Yanqiang WANG,Xiaorong GU,Chungang FENG,Rui HAO,Xiaoxiang HU,Ning LI

    2014-06-01

    Full Text Available The dermal hyperpigmentation phenotype in chickens is controlled by the dominant fibromelanosis allele. One of the ten unique characteristics of Silkie chickens is the fibromelanosis phenotype, which is pigmentation in the dermal layer of the skin and connective tissue. In this study, we found a mutation of fibromelanosis, a genomic rearrangement that included an inverted duplication of endothelin3 (EDN3, is responsible. We show that, as a stimulator of melanoblast proliferation, EDN3 expression was increased in silkie embryos and in both skin and muscle throughout adulthood. EDN3 expression led to an increase in expression of the downstream genes EDNRB2 and TYRP2, and was closely relate with the hyperpigmentation phenotype. We examined eight different Chinese chicken breeds showing hyperpigmentation and conclude that this structural genetic variant exists in all fibromelanosis chicken breeds.

  1. Open versus closed surgical exposure of canine teeth that are displaced in the roof of the mouth.

    Science.gov (United States)

    Parkin, Nicola; Benson, Philip E; Thind, Bikram; Shah, Anwar; Khalil, Ismail; Ghafoor, Saiba

    2017-08-21

    databases. We included randomised and quasi-randomised controlled trials assessing young people receiving surgical treatment to correct upper PDCs. There was no restriction on age, presenting malocclusion or type of active orthodontic treatment undertaken. We included unilaterally and bilaterally displaced canines. Two review authors independently screened the results of the electronic searches, extracted data and assessed the risk of bias in the included studies. We attempted to contact study authors for missing data or clarification where feasible. We followed statistical guidelines from the Cochrane Handbook for Systematic Reviews of Interventions for data synthesis. We included three studies, involving 146 participants. Two studies were assessed as being at high risk of bias.The main finding of the review was that the two techniques may be equally successful at exposing PDCs (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.93 to 1.06; three studies, 141 participants analysed, low-quality evidence).One surgical failure was due to detachment of the gold chain (closed group). One study reported on complications following surgery and found two in the closed group: a post-operative infection requiring antibiotics and pain during alignment of the canine as the gold chain penetrated through the gum tissue of the palate.We were unable to pool data for dental aesthetics, patient-reported pain and discomfort, periodontal health and treatment time; however, individual studies did not find any differences between the surgical techniques (low- to very low-quality evidence). Currently, the evidence suggests that neither the open or closed surgical technique for exposing palatally displaced maxillary canine teeth is superior for any of the outcomes included in this review; however, we considered the evidence to be low quality, with two of the three included studies being at high risk of bias. This suggests the need for more high-quality studies. Three ongoing clinical trials have

  2. Factors influencing efficiency of sliding mechanics to close extraction space: a systematic review.

    Science.gov (United States)

    Barlow, M; Kula, K

    2008-05-01

    To review recent literature to determine strength of clinical evidence concerning the influence of various factors on the efficiency (rate of tooth movement) of closing extraction spaces using sliding mechanics. A comprehensive systematic review on prospective clinical trials. An electronic search (1966-2006) of several databases limiting the searches to English and using several keywords was performed. Also a hand search of five key journals specifically searching for prospective clinical trials relevant to orthodontic space closure using sliding mechanics was completed. Outcome Measure - Rate of tooth movement. Ten prospective clinical trials comparing rates of closure under different variables and focusing only on sliding mechanics were selected for review. Of these ten trials on rate of closure, two compared arch wire variables, seven compared material variables used to apply force, and one examined bracket variables. Other articles which were not prospective clinical trials on sliding mechanics, but containing relevant information were examined and included as background information. CONCLUSION - The results of clinical research support laboratory results that nickel-titanium coil springs produce a more consistent force and a faster rate of closure when compared with active ligatures as a method of force delivery to close extraction space along a continuous arch wire; however, elastomeric chain produces similar rates of closure when compared with nickel-titanium springs. Clinical and laboratory research suggest little advantage of 200 g nickel-titanium springs over 150 g springs. More clinical research is needed in this area.

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

    Science.gov (United States)

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

    2018-01-01

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

  4. Open- and Closed-Skill Exercise Interventions Produce Different Neurocognitive Effects on Executive Functions in the Elderly: A 6-Month Randomized, Controlled Trial

    Directory of Open Access Journals (Sweden)

    Chia-Liang Tsai

    2017-09-01

    Full Text Available This study aimed to explore the effects of open- and closed-skill exercise interventions on the neurocognitive performance of executive functions in the elderly. Sixty-four healthy elderly males were randomly assigned to either a closed-skill (bike riding or brisk walking/jogging, n = 22, open-skill (table tennis, n = 21, or control (n = 21 group. Various neuropsychological [e.g., accuracy rates (AR and reaction time (RT] and electrophysiological [e.g., event-related potential (ERP P3 component] measures were assessed during a variant of the task-switching paradigm, as well as an N-back task at baseline and after either a 6-month exercise intervention or control period. The results showed that, when performing the task-switching paradigm, the two exercise groups relative to control group showed significantly faster RTs in the switch trials after the exercise intervention. However, the RT facilitation in the non-switch and switch trials post-exercise relative to pre-exercise only emerged in the open-skill group. In terms of the N-back task, the two exercise groups significantly increased ARs in the 1-back condition after the exercise intervention, and the beneficial AR effect on the 2-back condition only emerged in the closed-skill group. In addition, the two exercise groups exhibited significantly larger P3 amplitudes on the frontal-to-parietal cortex areas after the exercise intervention relative to the baseline when performing the two cognitive tasks. These neurocognitive results still remained unchanged even when the confounding factors (e.g., cardiorespiratory fitness, social participation, and BMI were controlled for. The present study concluded that, although 6-month open- and closed-skill exercise interventions facilitate overall electrophysiological effects (i.e., increased ERP P3 amplitudes on the frontal-to-parietal cortices in the elderly, the two exercise modes produced different levels of neuropsychologically beneficial effects on

  5. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis.

    Science.gov (United States)

    Delorme, Arnaud; Makeig, Scott

    2004-03-15

    We have developed a toolbox and graphic user interface, EEGLAB, running under the crossplatform MATLAB environment (The Mathworks, Inc.) for processing collections of single-trial and/or averaged EEG data of any number of channels. Available functions include EEG data, channel and event information importing, data visualization (scrolling, scalp map and dipole model plotting, plus multi-trial ERP-image plots), preprocessing (including artifact rejection, filtering, epoch selection, and averaging), independent component analysis (ICA) and time/frequency decompositions including channel and component cross-coherence supported by bootstrap statistical methods based on data resampling. EEGLAB functions are organized into three layers. Top-layer functions allow users to interact with the data through the graphic interface without needing to use MATLAB syntax. Menu options allow users to tune the behavior of EEGLAB to available memory. Middle-layer functions allow users to customize data processing using command history and interactive 'pop' functions. Experienced MATLAB users can use EEGLAB data structures and stand-alone signal processing functions to write custom and/or batch analysis scripts. Extensive function help and tutorial information are included. A 'plug-in' facility allows easy incorporation of new EEG modules into the main menu. EEGLAB is freely available (http://www.sccn.ucsd.edu/eeglab/) under the GNU public license for noncommercial use and open source development, together with sample data, user tutorial and extensive documentation.

  6. Studies of effects of closed microbial ecology. Report of 180-day test period

    Science.gov (United States)

    Kenyon, A. J.

    1972-01-01

    Experiments were performed to determine the influence closed microbial ecologies have on modification or simplification of natural intestinal flora of ferrets in a closed environmental system. On the basis of previous tests in which certain species (Salmonella and Bacteroides) were decreased at 90 days of enclosure, a second trial was constructed for 180-day tests. In this trial there was little difference in the 8 major classes of intestinal flora between animals in the Open and Closed environmental groups except for the level of Lactobacillus. It is of extreme importance to note that when both Open and Closed groups contracted hemorrhagic gastritis, the interrelationship of this agent with other intestinal flora produced a more profound effect on animals from the Closed Group, particularly with reference to Lactobacillus levels.

  7. Conservative management following closed reduction of traumatic anterior dislocation of the shoulder.

    Science.gov (United States)

    Hanchard, Nigel C A; Goodchild, Lorna M; Kottam, Lucksy

    2014-04-30

    Acute anterior dislocation, which is the most common type of shoulder dislocation, usually results from an injury. Subsequently, the shoulder is less stable and is more susceptible to re-dislocation, especially in active young adults. This is an update of a Cochrane review first published in 2006. To assess the effects (benefits and harms) of conservative interventions after closed reduction of traumatic anterior dislocation of the shoulder. These might include immobilisation, rehabilitative interventions or both. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (September 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 8), MEDLINE (1946 to September 2013), EMBASE (1980 to Week 38, 2013), CINAHL (1982 to September 2013), PEDro (1929 to November 2012), OTseeker (inception to November 2012) and trial registries. We also searched conference proceedings and reference lists of included studies. Randomised or quasi-randomised controlled trials comparing various conservative interventions versus control (no or sham treatment) or other conservative interventions applied after closed reduction of traumatic anterior dislocation of the shoulder. All review authors independently selected trials, assessed risk of bias and extracted data. Study authors were contacted for additional information. Results of comparable groups of trials were pooled. We included three randomised trials and one quasi-randomised trial, which involved 470 participants (371 male) with primary traumatic anterior dislocation of the shoulder reduced by various closed methods. Three studies evaluated mixed populations; in the fourth study, all participants were male and 80% were soldiers. All trials were at some risk of bias but to a differing extent. One was at high risk in all domains of the risk of bias tool, and one was at unclear or high risk in all domains; the other two trials were deemed to have predominantly low risk across all

  8. Clinical Trials

    Medline Plus

    Full Text Available ... care providers might be part of your treatment team. They will monitor your health closely. You may ... taking part in a clinical trial. Your treatment team also may ask you to do other tasks. ...

  9. Robustness assessments are needed to reduce bias in meta-analyses that include zero-event randomized trials

    DEFF Research Database (Denmark)

    Keus, F; Wetterslev, J; Gluud, C

    2009-01-01

    of statistical method on inference. RESULTS: In seven meta-analyses of seven outcomes from 15 trials, there were zero-event trials in 0 to 71.4% of the trials. We found inconsistency in significance in one of seven outcomes (14%; 95% confidence limit 0.4%-57.9%). There was also considerable variability......OBJECTIVES: Meta-analysis of randomized trials with binary data can use a variety of statistical methods. Zero-event trials may create analytic problems. We explored how different methods may impact inferences from meta-analyses containing zero-event trials. METHODS: Five levels of statistical...... methods are identified for meta-analysis with zero-event trials, leading to numerous data analyses. We used the binary outcomes from our Cochrane review of randomized trials of laparoscopic vs. small-incision cholecystectomy for patients with symptomatic cholecystolithiasis to illustrate the influence...

  10. Do pigeons prefer alternatives that include near-hit outcomes?

    Science.gov (United States)

    Stagner, Jessica P; Case, Jacob P; Sticklen, Mary F; Duncan, Amanda K; Zentall, Thomas R

    2015-07-01

    Pigeons show suboptimal choice on a gambling-like task similar to that shown by humans. Humans also show a preference for gambles in which there are near hits (losses that come close to winning). In the present research, we asked if pigeons would show a preference for alternatives with near-hit-like trials. In Experiment 1, we included an alternative that presented a near hit, in which a stimulus associated with reinforcement (a presumed conditioned reinforcer) changed to a stimulus associated with the absence of reinforcement (a presumed conditioned inhibitor). The pigeons tended to avoid this alternative. In Experiment 2, we varied the duration of the presumed conditioned reinforcer (2 vs. 8 s) that changed to a presumed conditioned inhibitor (8 vs. 2 s) and found that the longer the conditioned reinforcer was presented, the more the pigeons avoided it. In Experiment 3, the near-hit alternative involved an ambiguous stimulus for 8 s that changed to a presumed conditioned reinforcer (or a presumed conditioned inhibitor) for 2 s, but the pigeons still avoided it. In Experiment 4, we controlled for the duration of the conditioned reinforcer by presenting it first for 2 s followed by the ambiguous stimulus for 8 s. Once again, the pigeons avoided the alternative with the near-hit trials. In all 4 experiments, the pigeons tended to avoid alternatives that provided near-hit-like trials. We concluded that humans may be attracted to near-hit trials because near-hit trials give them the illusion of control, whereas this does not appear to be a factor for pigeons. (c) 2015 APA, all rights reserved).

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

    Science.gov (United States)

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

    2016-04-01

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

  12. Closing the knowledge gap on cardiovascular disease in type 2 diabetes: the EMPA-REG OUTCOME trial and beyond

    Directory of Open Access Journals (Sweden)

    Elif A Oral

    2016-09-01

    Full Text Available Type 2 diabetes mellitus (T2DM is associated with marked cardiovascular (CV morbidity and mortality, including heartfailure (HF. Until recently, an oral glucose-lowering agent that improved hyperglycemia as well as provided CV benefits in patients with T2DM and cardiovascular disease (CVD was lacking. The newest class of glucose-lowering agents, sodium glucose cotransporter 2 (SGLT2 inhibitors, includes canagliflozin, dapagliflozin, and empagliflozin. Prior to the release of the LEADER trial results, the recent EMPA-REG OUTCOME study was the only dedicated CV trial to demonstrate a reduction in major adverse cardiac events, CV mortality, and all-cause mortality and a reduction in hospitalization for HF with empagliflozin, given on top of standard-of-care therapy in patients with T2DM and CVD. This paper summarizes the results from EMPA-REG OUTCOME and discusses their significance and clinical implications.

  13. Systematic review and meta-analysis of closed suction drainage versus non-drainage in primary hip arthroplasty.

    LENUS (Irish Health Repository)

    Kelly, Enda G

    2014-03-01

    The routine use of drains in surgery has been dogmatically instituted in some disciplines. Orthopaedic surgery is one such sub-speciality. The use of postoperative closed suction drainage in total hip arthroplasty (THA) has become increasingly controversial with multiple randomised control trials performed to assess the benefit to outcome in THA. The hypothesis of this systematic review is that closed suction drainage does not infer a benefit and increase transfusion requirements of primary total hip arthroplasty patients. A systematic review and meta-analysis was conducted adhering to the PRISMA guidelines. A search of the available literature was performed on PubMed, Cochrane Central Registry of Controlled Trials, MEDLINE (OVID) and EMBASE using a combination of MeSH terms and Boolean operators. All data analysis was performed using the Cochrane Collaboration\\'s Review Manager 5.1. Sixteen studies (n=2705) were included in the analysis. Post-operative closed suction drainage was found to increase total blood loss and blood transfusion requirements (p<0.05). Surgical site infection demonstrated no significant difference between the two groups (p=0.82). No significant difference in haematoma formation between groups (p=0.19) was elicited. The routine use of closed suction drainage systems post primary hip arthroplasty is not supported by this meta-analysis. However, the heterogeneity between studies does limit the accuracy of the meta-analysis.

  14. Stem cells in clinical trials for treatment of retinal degeneration.

    Science.gov (United States)

    Klassen, Henry

    2016-01-01

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

  15. Closing the mycetoma knowledge gap.

    Science.gov (United States)

    van de Sande, Wendy; Fahal, Ahmed; Ahmed, Sarah Abdalla; Serrano, Julian Alberto; Bonifaz, Alexandro; Zijlstra, Ed

    2018-04-01

    On 28th May 2016, mycetoma was recognized as a neglected tropical disease by the World Health Organization. This was the result of a 4-year journey starting in February 2013 with a meeting of global mycetoma experts. Knowledge gaps were identified and included the incidence, prevalence, and mapping of mycetoma; the mode of transmission; the development of methods for early diagnosis; and better treatment. In this review, we review the road to recognition, the ISHAM working group meeting in Argentina, and we address the progress made in closing the knowledge gaps since 2013. Progress included adding another 9000 patients to the literature, which allowed us to update the prevalence map on mycetoma. Furthermore, based on molecular phylogeny, species names were corrected and four novel mycetoma causative agents were identified. By mapping mycetoma causative agents an association with Acacia trees was found. For early diagnosis, three different isothermal amplification techniques were developed, and novel antigens were discovered. To develop better treatment strategies for mycetoma patients, in vitro susceptibility tests for the coelomycete agents of black grain mycetoma were developed, and the first randomized clinical trial for eumycetoma started early 2017.

  16. Clinical Trials

    Medline Plus

    Full Text Available ... taking the same treatment the same way. These patients are closely watched by Data and Safety Monitoring Boards. Even if you don't directly ... risk procedures (such as gene therapy) or vulnerable patients (such as ... trial for safety problems or differences in results among different groups. ...

  17. Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: Mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05)

    International Nuclear Information System (INIS)

    Roos, Daniel E.; Wirth, Andrew; Burmeister, Bryan H.; Spry, Nigel A.; Drummond, Katharine J.; Beresford, Jennifer A.; McClure, Beverley E.

    2006-01-01

    We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery or radiosurgery for solitary brain metastases in a Phase III multicentre trial with randomization to 30-36 Gy WBI or observation. The study was closed early due to slow accrual after 19 patients (WBI 10, observation 9). There was no difference in CNS failure-free survival or overall survival between the arms. There was a trend to reduced CNS relapse with WBI (30% versus 78%, P = 0.12). Limited analysis of quality of life and neurocognitive function data revealed no evidence of difference between the arms. Our results are not inconsistent with two larger randomized trials and support the use of upfront WBI to decrease brain recurrence in this setting

  18. 77 FR 59405 - National Institute on Deafness and Other Communication Disorders; Notice of Closed Meetings

    Science.gov (United States)

    2012-09-27

    ... Deafness and Other Communication Disorders; Notice of Closed Meetings Pursuant to section 10(d) of the... Deafness and Other Communication Disorders Special Emphasis Panel; Hearing--Clinical Trials & Translational... Other Communication Disorders Special Emphasis Panel; Vestibular--Clinical Trials. Date: October 23...

  19. An integrated approach to consumer representation and involvement in a multicentre randomized controlled trial.

    Science.gov (United States)

    Langston, Anne L; McCallum, Marilyn; Campbell, Marion K; Robertson, Clare; Ralston, Stuart H

    2005-01-01

    Although, consumer involvement in individual studies is often limited, their involvement in guiding health research is generally considered to be beneficial. This paper outlines our experiences of an integrated relationship between the organisers of a clinical trial and a consumer organisation. The PRISM trial is a UK multicentre, randomized controlled trial comparing treatment strategies for Paget's disease of the bone. The National Association for the Relief of Paget's Disease (NARPD) is the only UK support group for sufferers of Paget's disease and has worked closely with the PRISM team from the outset. NARPD involvement is integral to the conduct of the trial and specific roles have included: peer-review; trial steering committee membership; provision of advice to participants, and promotion of the trial amongst Paget's disease patients. The integrated relationship has yielded benefits to both the trial and the consumer organisation. The benefits for the trial have included: recruitment of participants via NARPD contacts; well-informed participants; unsolicited patient advocacy of the trial; and interested and pro-active collaborators. For the NARPD and Paget's disease sufferers, benefits have included: increased awareness of Paget's disease; increased access to relevant health research; increased awareness of the NARPD services; and wider transfer of diagnosis and management knowledge to/from health care professionals. Our experience has shown that an integrated approach between a trial team and a consumer organisation is worthwhile. Adoption of such an approach in other trials may yield significant improvements in recruitment and quality of participant information flow. There are, however, resource implications for both parties.

  20. Effect of closed drainage system on edema and ecchymosis following rhinoplasty: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Kamran Asadi

    2013-08-01

    Full Text Available Background: The aim of this study was to minimize edema and ecchymosis following rhinoplasty through a closed drainage system to address concealed hemorrhage.Methods: This study was designed as a prospective، double blinded, randomized contr-olled study. Fifty one patients who underwent septorhinoplasty were included in this study and divided in two groups. In group A, a closed drainage system was applied in the most dependent posterior septal area following septal harvesting. Concealed bloody secretions were drained out of mouth in a vacutaner tube during three concecutive post operative days. In control group, group B, exactly the same classic rhinoplasty opera-tion by the same surgeon was done as for study group except omitting the closed drainage system. Degree of supra-tip and eyelid edema was evaluated on post operative days through photographic and software image analysis. Edema and ecchymosis rating of eyelids and ecchymosis of paranasal and cheek area done based on photographic analysis by independent plastic surgeons using a defined grading system.Results: Eyelid ecchymosis was reduced significantly on post operative day 14 in the study group (P=0.03. Ecchymosis of paranasal and check was reduced considerably likewise on days 7 and 14 in group A using Mann-Whitney test (P=0.03. There was no significant deference regarding supra tip edema on post operative days. The same hold true for the eyelids edema.Conclusion: Significant decrement observed in eyelids ecchymosis on day 14 and para-nasal and cheek ecchymosis on postoperative days 7 and 14 in study group. There were no positive effects regarding supra tip and eyelid edema reduction using closed drainage system to evacuate concealed haemorrhage in posterior septum space. There could be different etio-pathologies for two common morbidities following rhinoplasty that should be addressed separately.

  1. Alien wavelength modeling tool and field trial

    DEFF Research Database (Denmark)

    Sambo, N.; Sgambelluri, A.; Secondini, M.

    2015-01-01

    A modeling tool is presented for pre-FEC BER estimation of PM-QPSK alien wavelength signals. A field trial is demonstrated and used as validation of the tool's correctness. A very close correspondence between the performance of the field trial and the one predicted by the modeling tool has been...

  2. Including health equity considerations in development of instruments for rheumatology research

    DEFF Research Database (Denmark)

    O'Neill, Jennifer; Rader, Tamara; Guillemin, Francis

    2014-01-01

    The Outcome Measures in Rheumatology (OMERACT) Equity Special Interest Group (SIG) was established in 2008 to create a preliminary core set of outcome measures for clinical trials that can assess equity gaps in healthcare and the effectiveness of interventions to close or narrow gaps between...

  3. Clinical Trials

    Medline Plus

    Full Text Available ... medical strategy, treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ...

  4. Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project.

    Science.gov (United States)

    Hanning, Sara M; Orlu Gul, Mine; Winslade, Jackie; Baarslag, Manuel A; Neubert, Antje; Tuleu, Catherine

    2016-09-25

    A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Evolution of poor reporting and inadequate methods over time in 20 920 randomised controlled trials included in Cochrane reviews: research on research study.

    Science.gov (United States)

    Dechartres, Agnes; Trinquart, Ludovic; Atal, Ignacio; Moher, David; Dickersin, Kay; Boutron, Isabelle; Perrodeau, Elodie; Altman, Douglas G; Ravaud, Philippe

    2017-06-08

    Objective  To examine how poor reporting and inadequate methods for key methodological features in randomised controlled trials (RCTs) have changed over the past three decades. Design  Mapping of trials included in Cochrane reviews. Data sources  Data from RCTs included in all Cochrane reviews published between March 2011 and September 2014 reporting an evaluation of the Cochrane risk of bias items: sequence generation, allocation concealment, blinding, and incomplete outcome data. Data extraction  For each RCT, we extracted consensus on risk of bias made by the review authors and identified the primary reference to extract publication year and journal. We matched journal names with Journal Citation Reports to get 2014 impact factors. Main outcomes measures  We considered the proportions of trials rated by review authors at unclear and high risk of bias as surrogates for poor reporting and inadequate methods, respectively. Results  We analysed 20 920 RCTs (from 2001 reviews) published in 3136 journals. The proportion of trials with unclear risk of bias was 48.7% for sequence generation and 57.5% for allocation concealment; the proportion of those with high risk of bias was 4.0% and 7.2%, respectively. For blinding and incomplete outcome data, 30.6% and 24.7% of trials were at unclear risk and 33.1% and 17.1% were at high risk, respectively. Higher journal impact factor was associated with a lower proportion of trials at unclear or high risk of bias. The proportion of trials at unclear risk of bias decreased over time, especially for sequence generation, which fell from 69.1% in 1986-1990 to 31.2% in 2011-14 and for allocation concealment (70.1% to 44.6%). After excluding trials at unclear risk of bias, use of inadequate methods also decreased over time: from 14.8% to 4.6% for sequence generation and from 32.7% to 11.6% for allocation concealment. Conclusions  Poor reporting and inadequate methods have decreased over time, especially for sequence generation

  6. Behaviour and design considerations for continuous flow closed-open-closed liquid microchannels.

    Science.gov (United States)

    Melin, Jessica; van der Wijngaart, Wouter; Stemme, Göran

    2005-06-01

    This paper introduces a method of combining open and closed microchannels in a single component in a novel way which couples the benefits of both open and closed microfluidic systems and introduces interesting on-chip microfluidic behaviour. Fluid behaviour in such a component, based on continuous pressure driven flow and surface tension, is discussed in terms of cross sectional flow behaviour, robustness, flow-pressure performance, and its application to microfluidic interfacing. The closed-open-closed microchannel possesses the versatility of upstream and downstream closed microfluidics along with open fluidic direct access. The device has the advantage of eliminating gas bubbles present upstream when these enter the open channel section. The unique behaviour of this device opens the door to applications including direct liquid sample interfacing without the need for additional and bulky sample tubing.

  7. Lab-scale experiment of a closed thermochemical heat storage system including honeycomb heat exchanger

    International Nuclear Information System (INIS)

    Fopah-Lele, Armand; Rohde, Christian; Neumann, Karsten; Tietjen, Theo; Rönnebeck, Thomas; N'Tsoukpoe, Kokouvi Edem; Osterland, Thomas; Opel, Oliver

    2016-01-01

    A lab-scale thermochemical heat storage reactor was developed in the European project “thermal battery” to obtain information on the characteristics of a closed heat storage system, based on thermochemical reactions. The present type of storage is capable of re-using waste heat from cogeneration system to produce useful heat for space heating. The storage material used was SrBr 2 ·6H 2 O. Due to agglomeration or gel-like problems, a structural element was introduced to enhance vapour and heat transfer. Honeycomb heat exchanger was designed and tested. 13 dehydration-hydration cycles were studied under low-temperature conditions (material temperatures < 100 °C) for storage. Discharging was realized at water vapour pressure of about 42 mbar. Temperature evolution inside the reactor at different times and positions, chemical conversion, thermal power and overall efficiency were analysed for the selected cycles. Experimental system thermal capacity and efficiency of 65 kWh and 0.77 are respectively obtained with about 1 kg of SrBr 2 ·6H 2 O. Heat transfer fluid recovers heat at a short span of about 43 °C with an average of 22 °C during about 4 h, acceptable temperature for the human comfort (20 °C on day and 16 °C at night). System performances were obtained for a salt bed energy density of 213 kWh·m 3 . The overall heat transfer coefficient of the honeycomb heat exchanger has an average value of 147 W m −2  K −1 . Though promising results have been obtained, ameliorations need to be made, in order to make the closed thermochemical heat storage system competitive for space heating. - Highlights: • Lab-scale thermochemical heat storage is designed, constructed and tested. • The use of honeycomb heat exchanger as a heat and vapour process enhancement. • Closed system (1 kg SrBr 2 ·6H 2 O) able to give back 3/4 of initial thermal waste energy. • System storage capacity and thermal efficiency are respectively 65 kWh and 0.77.

  8. Clinical Trials

    Medline Plus

    Full Text Available ... sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include Government Agencies, ... and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including the NHLBI) usually ...

  9. Clinical Trials

    Medline Plus

    Full Text Available ... including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study explored ... risks. Other examples of clinical trials that test principles or strategies include studies that explore whether surgery ...

  10. Clinical Trials

    Medline Plus

    Full Text Available ... criteria differ from trial to trial. They include factors such as a patient's age and gender, the ... bias. "Bias" means that human choices or other factors not related to the protocol affect the trial's ...

  11. An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

    Directory of Open Access Journals (Sweden)

    Moore Simon C

    2012-06-01

    Full Text Available Abstract Background To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation. Methods An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews. Results The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises. Conclusions It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability. Trial registration UKCRN 7090; ISRCTN: 80875696

  12. Do we have to Include HCI Issues in Clinical Trials of Medical Devices?

    DEFF Research Database (Denmark)

    Nielsen, Lene; Christensen, Lars Rune; Sabers, Anne

    2017-01-01

    Digital devices play an important role in medical treatment and will in the future play a larger role in connection to cures of health-related issues. Traditionally medicine has been tested by clinical double blind, randomized trials to document the efficacy and safety profile. When it comes to t...

  13. Time to consider sharing data extracted from trials included in systematic reviews

    Directory of Open Access Journals (Sweden)

    Luke Wolfenden

    2016-11-01

    Full Text Available Abstract Background While the debate regarding shared clinical trial data has shifted from whether such data should be shared to how this is best achieved, the sharing of data collected as part of systematic reviews has received little attention. In this commentary, we discuss the potential benefits of coordinated efforts to share data collected as part of systematic reviews. Main body There are a number of potential benefits of systematic review data sharing. Shared information and data obtained as part of the systematic review process may reduce unnecessary duplication, reduce demand on trialist to service repeated requests from reviewers for data, and improve the quality and efficiency of future reviews. Sharing also facilitates research to improve clinical trial and systematic review methods and supports additional analyses to address secondary research questions. While concerns regarding appropriate use of data, costs, or the academic return for original review authors may impede more open access to information extracted as part of systematic reviews, many of these issues are being addressed, and infrastructure to enable greater access to such information is being developed. Conclusion Embracing systems to enable more open access to systematic review data has considerable potential to maximise the benefits of research investment in undertaking systematic reviews.

  14. Close binary stars

    International Nuclear Information System (INIS)

    Larsson-Leander, G.

    1979-01-01

    Studies of close binary stars are being persued more vigorously than ever, with about 3000 research papers and notes pertaining to the field being published during the triennium 1976-1978. Many major advances and spectacular discoveries were made, mostly due to increased observational efficiency and precision, especially in the X-ray, radio, and ultraviolet domains. Progress reports are presented in the following areas: observational techniques, methods of analyzing light curves, observational data, physical data, structure and models of close binaries, statistical investigations, and origin and evolution of close binaries. Reports from the Coordinates Programs Committee, the Committee for Extra-Terrestrial Observations and the Working Group on RS CVn binaries are included. (Auth./C.F.)

  15. The Role of Oncology Nurses in Discussing Clinical Trials.

    Science.gov (United States)

    Flocke, Susan A; Antognoli, Elizabeth; Daly, Barbara J; Jackson, Brigid; Fulton, Sarah E; Liu, Tasnuva M; Surdam, Jessica; Manne, Sharon; Meropol, Neal J

    2017-09-01

    To describe oncology nurses' experiences discussing clinical trials with their patients, and to assess barriers to these discussions.
. A qualitative study designed to elicit narratives from oncology nurses. 
. Community- and academic-based oncology clinics throughout the United States.
. 33 oncology nurses involved in direct patient care in community-based and large hospital-based settings. The sample was drawn from members of the Oncology Nursing Society. 
. In-depth interviews were conducted and analyzed using a 
immersion/crystallization approach to identify themes and patterns. The analyses highlight specific issues, examples, and contexts that present challenges to clinical trial discussions with patients.
. Oncology nurses view their roles as patient educators and advocates to be inclusive of discussion of clinical trials. Barriers to such discussions include lack of knowledge and strategies for addressing patients' common misconceptions and uncertainty about the timing of discussions.
. These data indicate that enabling nurses to actively engage patients in discussions of clinical trials requires educational interventions to build self-efficacy and close knowledge gaps. 
. Oncology nurses can play a critical role in advancing cancer care by supporting patients in decision making about clinical trial participation. This will require training and education to build their knowledge, reduce barriers, and increase their self-efficacy to fulfill this responsibility in various clinical settings.

  16. Published intimate partner violence studies often differ from their trial registration records.

    Science.gov (United States)

    Madden, Kim; Tai, Kerry; Ali, Zak; Schneider, Patricia; Singh, Mahip; Ghert, Michelle; Bhandari, Mohit

    2017-12-27

    Registering study protocols in a trial registry is important for methodologic transparency and reducing selective reporting bias. The objective of this investigation was to determine whether published studies of intimate partner violence (IPV) that had been registered matched the registration record on key study design elements. We systematically searched three trial registries to identify registered IPV studies and the published literature for the associated publication. Two authors independently determined for each study whether key study elements in the registry matched those in the published paper. We included 66 studies published between 2006 and 2017. Nearly half (29/66, 44%) were registered after study completion. Many (26/66, 39%) had discrepancies regarding the primary outcome, and nearly two-thirds (42/66, 64%) had discrepancies in secondary outcomes. Discrepancies in study design were less frequent (13/66, 20%). However, large changes in sample size (26/66, 39%) and discrepancies in funding source (28/66, 42%) were frequently observed. Trial registries are important tools for research transparency and identifying and preventing outcome switching and selective outcome reporting bias. Published IPV studies often differ from their records in trial registries. Researchers should pay close attention to the accuracy of trial registry records.

  17. 77 FR 31862 - National Center for Complementary & Alternative Medicine; Notice of Closed Meetings

    Science.gov (United States)

    2012-05-30

    ... Complementary & Alternative Medicine; Notice of Closed Meetings Pursuant to section 10(d) of the Federal... Scientific Review, National Center for Complementary and Alternative Medicine, NIH, 6707 Democracy Blvd... for Complementary and Alternative Medicine Special Emphasis Panel; HCS Collaboratory Pragmatic Trials...

  18. Types of Cancer Clinical Trials

    Science.gov (United States)

    Information about the several types of cancer clinical trials, including treatment trials, prevention trials, screening trials, supportive and palliative care trials. Each type of trial is designed to answer different research questions.

  19. Successful recruitment to trials: findings from the SCIMITAR+ Trial.

    Science.gov (United States)

    Peckham, Emily; Arundel, Catherine; Bailey, Della; Callen, Tracy; Cusack, Christina; Crosland, Suzanne; Foster, Penny; Herlihy, Hannah; Hope, James; Ker, Suzy; McCloud, Tayla; Romain-Hooper, Crystal-Bella; Stribling, Alison; Phiri, Peter; Tait, Ellen; Gilbody, Simon

    2018-01-19

    Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment.

  20. Customization of home closed-loop insulin delivery in adult patients with type 1 diabetes, assisted with structured remote monitoring: the pilot WP7 Diabeloop study.

    Science.gov (United States)

    Benhamou, Pierre Yves; Huneker, Erik; Franc, Sylvia; Doron, Maeva; Charpentier, Guillaume

    2018-06-01

    Improvement in closed-loop insulin delivery systems could result from customization of settings to individual needs and remote monitoring. This pilot home study evaluated the efficacy and relevance of this approach. A bicentric clinical trial was conducted for 3 weeks, using an MPC-based algorithm (Diabeloop Artificial Pancreas system) featuring five settings designed to modulate the reactivity of regulation. Remote monitoring was ensured by expert nurses with a web platform generating automatic Secured Information Messages (SIMs) and with a structured procedure. Endpoints were glucose metrics and description of impact of monitoring on regulation parameters. Eight patients with type 1 diabetes (six men, age 41.8 ± 11.4 years, HbA1c 7.7 ± 1.0%) were included. Time spent in the 70-180 mg/dl range was 70.2% [67.5; 76.9]. Time in hypoglycemia < 70 mg/dl was 2.9% [2.1; 3.4]. Eleven SIMs led to phone intervention. Original default settings were modified in all patients by the intervention of the nurses. This pilot trial suggests that the Diabeloop closed-loop system could be efficient regarding metabolic outcomes, whereas its telemedical monitoring feature could contribute to enhanced efficacy and safety. This study is registered at ClinicalTrials.gov with trial registration number NCT02987556.

  1. Closed recirculation-Water treatment

    International Nuclear Information System (INIS)

    Hamza, Hamza B.; Ben Ali, Salah; Saad, Mohamed A.; Traish, Massud R.

    2005-01-01

    This water treatment is a practical work applied in the center, for a closed recirculation-water system. The system had experienced a serious corrosion problem, due to the use of inadequate water. This work includes chemical preparation for the system. Water treatment, special additives, and follow-up, which resulted in the stability of the case. This work can be applied specially for closed recirculation warm, normal, and chilled water. (author)

  2. Normative values for the unipedal stance test with eyes open and closed.

    Science.gov (United States)

    Springer, Barbara A; Marin, Raul; Cyhan, Tamara; Roberts, Holly; Gill, Norman W

    2007-01-01

    Limited normative data are available for the unipedal stance test (UPST), making it difficult for clinicians to use it confidently to detect subtle balance impairments. The purpose of this study was to generate normative values for repeated trials of the UPST with eyes opened and eyes closed across age groups and gender. This prospective, mixed-model design was set in a tertiary care medical center. Healthy subjects (n= 549), 18 years or older, performed the UPST with eyes open and closed. Mean and best of 3 UPST times for males and females of 6 age groups (18-39, 40-49, 50-59, 60-69, 70-79, and 80+) were documented and inter-rater reliability was tested. There was a significant age dependent decrease in UPST time during both conditions. Inter-rater reliability for the best of 3 trials was determined to be excellent with an intra-class correlation coefficient of 0.994 (95% confidence interval 0.989-0.996) for eyes open and 0.998 (95% confidence interval 0.996-0.999) for eyes closed. This study adds to the understanding of typical performance on the UPST. Performance is age-specific and not related to gender. Clinicians now have more extensive normative values to which individuals can be compared.

  3. Moxibustion for cephalic version: a feasibility randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Bisits Andrew

    2011-09-01

    Full Text Available Abstract Background Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin has been used to correct a breech presentation. Evidence of effectiveness and safety from systematic reviews is encouraging although significant heterogeneity has been found among trials. We assessed the feasibility of conducting a randomised controlled trial of moxibustion plus usual care compared with usual care to promote cephalic version in women with a breech presentation, and examined the views of women and health care providers towards implementing a trial within an Australian context. Methods The study was undertaken at a public hospital in Newcastle, New South Wales, Australia. Women at 34-36.5 weeks of gestation with a singleton breech presentation (confirmed by ultrasound, were randomised to moxibustion plus usual care or usual care alone. The intervention was administered over 10 days. Clinical outcomes included cephalic presentation at birth, the need for ECV, mode of birth; perinatal morbidity and mortality, and maternal complications. Feasibility outcomes included: recruitment rate, acceptability, compliance and a sample size for a future study. Interviews were conducted with 19 midwives and obstetricians to examine the acceptability of moxibustion, and views on the trial. Results Twenty women were randomised to the trial. Fifty one percent of women approached accepted randomisation to the trial. A trend towards an increase in cephalic version at delivery (RR 5.0; 95% CI 0.7-35.5 was found for women receiving moxibustion compared with usual care. There was also a trend towards greater success with version following ECV. Two babies were admitted to the neonatal unit from the moxibustion group. Compliance with the moxibustion protocol was acceptable with no reported side effects. Clinicians expressed the need for research to establish the safety and efficacy of moxibustion, and support for the intervention was given to

  4. Closed string field theory

    International Nuclear Information System (INIS)

    Strominger, A.

    1987-01-01

    A gauge invariant cubic action describing bosonic closed string field theory is constructed. The gauge symmetries include local spacetime diffeomorphisms. The conventional closed string spectrum and trilinear couplings are reproduced after spontaneous symmetry breaking. The action S is constructed from the usual ''open string'' field of ghost number minus one half. It is given by the associator of the string field product which is non-vanishing because of associativity anomalies. S does not describe open string propagation because open string states associate and can thereby be shifted away. A field theory of closed and open strings can be obtained by adding to S the cubic open string action. (orig.)

  5. Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

    Science.gov (United States)

    Kramer, George C.; Wade, Charles E.; Dubick, Michael A.; Atkins, James L.

    2004-01-01

    Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure blood use and lower mortality compared to historic controls of patients refusing blood. Transfusion reductions with HBOC use have been modest. Two HBOCs (Hemopure and Polyheme) are now in new or planned large-scale multicenter prehospital trials of trauma treatment. A new implementation of small volume resuscitation is closed-loop resuscitation (CLR), which employs microprocessors to titrate just enough fluid to reach a physiologic target . Animal studies suggest less risk of rebleeding in uncontrolled hemorrhage and a reduction in fluid needs with CLR. The first clinical application of CLR was treatment of burn shock and the US Army. Conclusions: Independently sponsored civilian trauma trials and clinical evaluations in operational combat conditions of

  6. Ecological Challenges for Closed Systems

    Science.gov (United States)

    Nelson, Mark; Dempster, William; Allen, John P.

    2012-07-01

    Closed ecological systems are desirable for a number of purposes. In space life support systems, material closure allows precious life-supporting resources to be kept inside and recycled. Closure in small biospheric systems facilitates detailed measurement of global ecological processes and biogeochemical cycles. Closed testbeds facilitate research topics which require isolation from the outside (e.g. genetically modified organisms; radioisotopes) so their ecological interactions and fluxes can be studied separate from interactions with the outside environment. But to achieve and maintain closure entails solving complex ecological challenges. These challenges include being able to handle faster cycling rates and accentuated daily and seasonal fluxes of critical life elements such as carbon dioxide, oxygen, water, macro- and mico-nutrients. The problems of achieving sustainability in closed systems for life support include how to handle atmospheric dynamics including trace gases, producing a complete human diet and recycling nutrients and maintaining soil fertility, the sustaining of healthy air and water and preventing the loss of crucial elements from active circulation. In biospheric facilities the challenge is also to produce analogues to natural biomes and ecosystems, studying processes of self-organization and adaptation in systems that allow specification or determination of state variables and cycles which may be followed through all interactions from atmosphere to soils. Other challenges include the dynamics and genetics of small populations, the psychological challenges for small isolated human groups and measures and options which may be necessary to ensure long-term operation of closed ecological systems.

  7. Design strategies for dynamic closed-loop optogenetic neurocontrol in vivo

    Science.gov (United States)

    Bolus, M. F.; Willats, A. A.; Whitmire, C. J.; Rozell, C. J.; Stanley, G. B.

    2018-04-01

    Objective. Controlling neural activity enables the possibility of manipulating sensory perception, cognitive processes, and body movement, in addition to providing a powerful framework for functionally disentangling the neural circuits that underlie these complex phenomena. Over the last decade, optogenetic stimulation has become an increasingly important and powerful tool for understanding neural circuit function, owing to the ability to target specific cell types and bidirectionally modulate neural activity. To date, most stimulation has been provided in open-loop or in an on/off closed-loop fashion, where previously-determined stimulation is triggered by an event. Here, we describe and demonstrate a design approach for precise optogenetic control of neuronal firing rate modulation using feedback to guide stimulation continuously. Approach. Using the rodent somatosensory thalamus as an experimental testbed for realizing desired time-varying patterns of firing rate modulation, we utilized a moving average exponential filter to estimate firing rate online from single-unit spiking measured extracellularly. This estimate of instantaneous rate served as feedback for a proportional integral (PI) controller, which was designed during the experiment based on a linear-nonlinear Poisson (LNP) model of the neuronal response to light. Main results. The LNP model fit during the experiment enabled robust closed-loop control, resulting in good tracking of sinusoidal and non-sinusoidal targets, and rejection of unmeasured disturbances. Closed-loop control also enabled manipulation of trial-to-trial variability. Significance. Because neuroscientists are faced with the challenge of dissecting the functions of circuit components, the ability to maintain control of a region of interest in spite of changes in ongoing neural activity will be important for disambiguating function within networks. Closed-loop stimulation strategies are ideal for control that is robust to such changes

  8. The role of technology in clinical trials using stereotactic body radiotherapy

    DEFF Research Database (Denmark)

    Aznar, Marianne; Romero, Alejandra Méndez; Heijmen, Ben J.M.

    2017-01-01

    , the crucial point for the next generation of SABR clinical trials is that today's technology is used correctly and close to its optimal potential for accuracy. The credentialing procedure of SABR needs to be extensive, but this investment will benefit the trial itself, the patients and the professionals...

  9. Clinical Trials

    Medline Plus

    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... include factors such as a patient's age and gender, the type and stage of disease, and whether ...

  10. Closing the antidepressant efficacy gap between clinical trials and real patient populations.

    Science.gov (United States)

    Wade, Alan G

    2006-01-01

    Overall, patient outcomes in the primary care of depression are seldom as good as those achieved in clinical trials - the "efficacy gap". Many factors contribute to this, including poor patient compliance, poor family and social support and negative media reporting of antidepressants. Indeed, negative media reporting has had far more impact on physicians' prescribing of antidepressants than have regulatory agencies, partly as a result of changing public attitudes. Negative media reports linking SSRIs to increased child suicide rates have also resulted in a decline in the prescribing of SSRIs to this age group, but with no concomitant increase in the prescribing of fluoxetine, the only antidepressant recommended for the treatment of children. There are also inadequacies in the guidelines available to primary care givers that might contribute to the efficacy gap. Guidelines can be too specific for clinical practice - especially where depression coexists with anxiety disorders - and too passive, resulting in delayed or inadequate intervention. Evidence suggests that many physicians prefer to be more proactive. In the recent AHEAD survey, physicians identified faster resolution of symptoms as the property most desirable for improving antidepressant therapy. There is recent evidence that structured long-term therapy and easily-implemented measurement-based care procedures can improve remission rates and help bridge the efficacy gap. If these can be allied with greater public/media understanding of depression and its treatment, along with improved guidelines, then significant progress can be anticipated in the management of mood disorders.

  11. Dem Generation from Close-Range Photogrammetry Using Extended Python Photogrammetry Toolbox

    Science.gov (United States)

    Belmonte, A. A.; Biong, M. M. P.; Macatulad, E. G.

    2017-10-01

    Digital elevation models (DEMs) are widely used raster data for different applications concerning terrain, such as for flood modelling, viewshed analysis, mining, land development, engineering design projects, to name a few. DEMs can be obtained through various methods, including topographic survey, LiDAR or photogrammetry, and internet sources. Terrestrial close-range photogrammetry is one of the alternative methods to produce DEMs through the processing of images using photogrammetry software. There are already powerful photogrammetry software that are commercially-available and can produce high-accuracy DEMs. However, this entails corresponding cost. Although, some of these software have free or demo trials, these trials have limits in their usable features and usage time. One alternative is the use of free and open-source software (FOSS), such as the Python Photogrammetry Toolbox (PPT), which provides an interface for performing photogrammetric processes implemented through python script. For relatively small areas such as in mining or construction excavation, a relatively inexpensive, fast and accurate method would be advantageous. In this study, PPT was used to generate 3D point cloud data from images of an open pit excavation. The PPT was extended to add an algorithm converting the generated point cloud data into a usable DEM.

  12. Clinical Trials

    Medline Plus

    Full Text Available ... organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and ... to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be ...

  13. Clinical Trials

    Medline Plus

    Full Text Available ... Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including ... our campus or trials NIH has sponsored at universities, medical centers, and hospitals. ClinicalTrials.gov View a ...

  14. Clinical Trials

    Medline Plus

    Full Text Available ... groups, companies, and organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments ... sponsor trials that test principles or strategies. For example, one NHLBI study explored whether the benefits of ...

  15. Clinical Trials

    Medline Plus

    Full Text Available ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ... U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers ( ...

  16. Clinical Trials

    Medline Plus

    Full Text Available ... people who fit the patient traits for that study (the eligibility criteria). Eligibility criteria differ from trial to trial. They include factors such as a patient's age and gender, the type and stage of disease, and whether ...

  17. Strategies to improve retention in randomised trials

    Science.gov (United States)

    Brueton, Valerie C; Tierney, Jayne; Stenning, Sally; Harding, Seeromanie; Meredith, Sarah; Nazareth, Irwin; Rait, Greta

    2013-01-01

    Background Loss to follow-up from randomised trials can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated. Objectives To quantify the effect of strategies to improve retention on the proportion of participants retained in randomised trials and to investigate if the effect varied by trial strategy and trial setting. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, EMBASE, PsycINFO, DARE, CINAHL, Campbell Collaboration's Social, Psychological, Educational and Criminological Trials Register, and ERIC. We handsearched conference proceedings and publication reference lists for eligible retention trials. We also surveyed all UK Clinical Trials Units to identify further studies. Selection criteria We included eligible retention trials of randomised or quasi-randomised evaluations of strategies to increase retention that were embedded in 'host' randomised trials from all disease areas and healthcare settings. We excluded studies aiming to increase treatment compliance. Data collection and analysis We contacted authors to supplement or confirm data that we had extracted. For retention trials, we recorded data on the method of randomisation, type of strategy evaluated, comparator, primary outcome, planned sample size, numbers randomised and numbers retained. We used risk ratios (RR) to evaluate the effectiveness of the addition of strategies to improve retention. We assessed heterogeneity between trials using the Chi2 and I2 statistics. For main trials that hosted retention trials, we extracted data on disease area, intervention, population, healthcare setting, sequence generation and allocation concealment. Main results We identified 38 eligible retention trials. Included trials evaluated six broad types of strategies to improve retention. These

  18. Experimental submarine with closed cycle diesel engine. Final report. Experimentaltauchboot mit Argon-Kreislaufdieselmotor. Schlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Haas, J.

    1990-08-01

    The Experimental Submarine SEAHORSE-KD is a fully operational autonomous test platform for an air independent propulsion system based on a closed cycle diesel engine. The Argon-Diesel known as MOTARK was a contribution from MAN Technologie AG, Munich, which also included process technology and control. Within the Argon cycle the exhaust gas is cooled down, cleaned from CO{sub 2} in a rotary scrubber and fed into the engine again after addition of oxygen. On surface, the engine can be operated on ambient air. During closed cycle operation, no media are exchanged with the ambient. The process works independently from the depth. Bruker Meerestechnik GmbH had to define the complete vehicle, developed and integrated the subsystems such as the LOX-system, the chemical and condensate plant, the fuel system, the propulsion and the electric system, etc. and carried out extensive workshop tests, shallow water and sea trials. The reliable functioning of the CCD-plant and of the complete Experimental Submarine could be convincingly demonstrated. A certificate has been issued by the Germanischer Lloyd. (orig.) With 90 refs., 15 figs.

  19. Artificial Pancreas Device Systems for the Closed-Loop Control of Type 1 Diabetes

    Science.gov (United States)

    Trevitt, Sara; Simpson, Sue; Wood, Annette

    2015-01-01

    Background: Closed-loop artificial pancreas device (APD) systems are externally worn medical devices that are being developed to enable people with type 1 diabetes to regulate their blood glucose levels in a more automated way. The innovative concept of this emerging technology is that hands-free, continuous, glycemic control can be achieved by using digital communication technology and advanced computer algorithms. Methods: A horizon scanning review of this field was conducted using online sources of intelligence to identify systems in development. The systems were classified into subtypes according to their level of automation, the hormonal and glycemic control approaches used, and their research setting. Results: Eighteen closed-loop APD systems were identified. All were being tested in clinical trials prior to potential commercialization. Six were being studied in the home setting, 5 in outpatient settings, and 7 in inpatient settings. It is estimated that 2 systems may become commercially available in the EU by the end of 2016, 1 during 2017, and 2 more in 2018. Conclusions: There are around 18 closed-loop APD systems progressing through early stages of clinical development. Only a few of these are currently in phase 3 trials and in settings that replicate real life. PMID:26589628

  20. Learning-based position control of a closed-kinematic chain robot end-effector

    Science.gov (United States)

    Nguyen, Charles C.; Zhou, Zhen-Lei

    1990-01-01

    A trajectory control scheme whose design is based on learning theory, for a six-degree-of-freedom (DOF) robot end-effector built to study robotic assembly of NASA hardwares in space is presented. The control scheme consists of two control systems: the feedback control system and the learning control system. The feedback control system is designed using the concept of linearization about a selected operating point, and the method of pole placement so that the closed-loop linearized system is stabilized. The learning control scheme consisting of PD-type learning controllers, provides additional inputs to improve the end-effector performance after each trial. Experimental studies performed on a 2 DOF end-effector built at CUA, for three tracking cases show that actual trajectories approach desired trajectories as the number of trials increases. The tracking errors are substantially reduced after only five trials.

  1. 77 FR 10540 - National Center for Complementary and Alternative Medicine Notice of Closed Meeting

    Science.gov (United States)

    2012-02-22

    ... Complementary and Alternative Medicine Notice of Closed Meeting Pursuant to section 10(d) of the Federal..., Research and Training in Complementary and Alternative Medicine, National Institutes of Health, HHS) Dated... Alternative Medicine Special Emphasis Panel; Research Resource for CAM Clinical Trials. Date: March 15, 2012...

  2. Sequential Multiple Assignment Randomized Trials: An Opportunity for Improved Design of Stroke Reperfusion Trials.

    Science.gov (United States)

    Meurer, William J; Seewald, Nicholas J; Kidwell, Kelley

    2017-04-01

    Modern clinical trials in stroke reperfusion fall into 2 categories: alternative systemic pharmacological regimens to alteplase and "rescue" endovascular approaches using targeted thrombectomy devices and/or medications delivered directly for persistently occluded vessels. Clinical trials in stroke have not evaluated how initial pharmacological thrombolytic management might influence subsequent rescue strategy. A sequential multiple assignment randomized trial (SMART) is a novel trial design that can test these dynamic treatment regimens and lead to treatment guidelines that more closely mimic practice. To characterize a SMART design in comparison to traditional approaches for stroke reperfusion trials. We conducted a numerical simulation study that evaluated the performance of contrasting acute stroke clinical trial designs of both initial reperfusion and rescue therapy. We compare a SMART design where the same patients are followed through initial reperfusion and rescue therapy within 1 trial to a standard phase III design comparing 2 reperfusion treatments and a separate phase II futility design of rescue therapy in terms of sample size, power, and ability to address particular research questions. Traditional trial designs can be well powered and have optimal design characteristics for independent treatment effects. When treatments, such as the reperfusion and rescue therapies, may interact, commonly used designs fail to detect this. A SMART design, with similar sample size to standard designs, can detect treatment interactions. The use of SMART designs to investigate effective and realistic dynamic treatment regimens is a promising way to accelerate the discovery of new, effective treatments for stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  3. Chiropractic treatment including instrument-assisted manipulation for non-specific dizziness and neck pain in community-dwelling older people: a feasibility randomised sham-controlled trial.

    Science.gov (United States)

    Kendall, Julie C; French, Simon D; Hartvigsen, Jan; Azari, Michael F

    2018-01-01

    Dizziness in older people is a risk factor for falls. Neck pain is associated with dizziness and responds favourably to neck manipulation. However, it is unknown if chiropractic intervention including instrument-assisted manipulation of the neck in older people with neck pain can also improve dizziness. This parallel two-arm pilot trial was conducted in Melbourne, Australia over nine months (October 2015 to June 2016). Participants aged 65-85 years, with self-reported chronic neck pain and dizziness, were recruited from the general public through advertisements in local community newspapers and via Facebook. Participants were randomised using a permuted block method to one of two groups: 1) Activator II™-instrument-assisted cervical and thoracic spine manipulation plus a combination of: light massage; mobilisation; range of motion exercises; and home advice about the application of heat, or 2) Sham-Activator II™-instrument-assisted manipulation (set to zero impulse) plus gentle touch of cervical and thoracic spinal regions. Participants were blinded to group allocation. The interventions were delivered weekly for four weeks. Assessments were conducted one week pre- and post-intervention. Clinical outcomes were assessed blindly and included: dizziness (dizziness handicap inventory [DHI]); neck pain (neck disability index [NDI]); self-reported concerns of falling; mood; physical function; and treatment satisfaction. Feasibility outcomes included recruitment rates, compliance with intervention and outcome assessment, study location, success of blinding, costs and harms. Out of 162 enquiries, 24 participants were screened as eligible and randomised to either the chiropractic ( n  = 13) or sham ( n  = 11) intervention group. Compliance was satisfactory with only two participants lost to follow up; thus, post-intervention data for 12 chiropractic intervention and 10 sham intervention participants were analysed. Blinding was similar between groups. Mild harms

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

    Science.gov (United States)

    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.

  5. Risk of bias assessment of randomised controlled trials in high-impact ophthalmology journals and general medical journals: a systematic review.

    Science.gov (United States)

    Joksimovic, Lazar; Koucheki, Robert; Popovic, Marko; Ahmed, Yusuf; Schlenker, Matthew B; Ahmed, Iqbal Ike K

    2017-10-01

    Evidence-based treatments in ophthalmology are often based on the results of randomised controlled trials. Biased conclusions from randomised controlled trials may lead to inappropriate management recommendations. This systematic review investigates the prevalence of bias risk in randomised controlled trials published in high-impact ophthalmology journals and ophthalmology trials from general medical journals. Using Ovid MEDLINE, randomised controlled trials in the top 10 high-impact ophthalmology journals in 2015 were systematically identified and critically appraised for the prevalence of bias risk. Included randomised controlled trials were assessed in all domains of bias as defined by the Cochrane Collaboration. In addition, the prevalence of conflict of interest and industry sponsorship was investigated. A comparison with ophthalmology articles from high-impact general medical journals was performed. Of the 259 records that were screened from ophthalmology-specific journals, 119 trials met all inclusion criteria and were critically appraised. In total, 29.4% of domains had an unclear risk, 13.8% had a high risk and 56.8% had a low risk of bias. In comparison, ophthalmology articles from general medical journals had a lower prevalence of unclear risk (17.1%), higher prevalence of high risk (21.9%) and a higher prevalence of low risk domains (61.9%). Furthermore, 64.7% of critically appraised trials from ophthalmology-specific journals did not report any conflicts of interest, while 70.6% did not report an industry sponsor of their trial. In closing, it is essential that authors, peer reviewers and readers closely follow published risk of bias guidelines. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Transition rates from schizotypal disorder to psychotic disorder for first-contact patients included in the OPUS trial. A randomized clinical trial of integrated treatment and standard treatment

    DEFF Research Database (Denmark)

    Nordentoft, Merete; Thorup, Anne; Petersen, Lone

    2006-01-01

    Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms.......Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms....

  7. Narrating the Mensalão trial

    DEFF Research Database (Denmark)

    Damgaard, Mads

    2015-01-01

    Coming to a close in the last days of 2012, the trial of the so-called mensalão network was heralded as Brazil's trial of the century. Involving corruption in the top ranks of the business world and the former government, the process ended with an exceptional result in the sense that severe...... sentences were meted out to 25 of the 38 defendants, thereby breaking an established pattern of impunity for corrupt politicians in Brazilian courts. As a scandal potentially harmful for the governing party and the former president Luis “Lula” da Silva, the eyes and spotlights of the national media were...... fixed on the trial. However, the varying and contested ways in which the case was presented by media from the outbreak of the scandal in 2005 until the end of the trial bears witness to the fact that narratives concerning corruption scandals can potentially encompass a broad range of political...

  8. A cluster-randomised trial of a multifaceted quality improvement intervention in Brazilian intensive care units (Checklist-ICU trial): statistical analysis plan.

    Science.gov (United States)

    Damiani, Lucas P; Cavalcanti, Alexandre B; Moreira, Frederico R; Machado, Flavia; Bozza, Fernando A; Salluh, Jorge I F; Campagnucci, Valquiria P; Normilio-Silva, Karina; Chiattone, Viviane C; Angus, Derek C; Berwanger, Otavio; Chou H Chang, Chung-

    2015-06-01

    The Checklist During Multidisciplinary Visits for Reduction of Mortality in Intensive Care Units (Checklist- ICU) trial is a pragmatic, two-arm, cluster-randomised trial involving 118 intensive care units in Brazil, with the primary objective of determining if a multifaceted qualityimprovement intervention with a daily checklist, definition of daily care goals during multidisciplinary daily rounds and clinician prompts can reduce inhospital mortality. To describe our trial statistical analysis plan (SAP). This is an ongoing trial conducted in two phases. In the preparatory observational phase, we collect three sets of baseline data: ICU characteristics; patient characteristics, processes of care and outcomes; and completed safety attitudes questionnaires (SAQs). In the randomised phase, ICUs are assigned to the experimental or control arms and we collect patient data and repeat the SAQ. Our SAP includes the prespecified model for the primary and secondary outcome analyses, which account for the cluster-randomised design and availability of baseline data. We also detail the multiple mediation models that we will use to assess our secondary hypothesis (that the effect of the intervention on inhospital mortality is mediated not only through care processes targeted by the checklist, but also through changes in safety culture). We describe our approach to sensitivity and subgroup analyses and missing data. We report our SAP before closing our study database and starting analysis. We anticipate that this should prevent analysis bias and enhance the utility of results.

  9. OARSI Clinical Trials Recommendations: Hand imaging in clinical trials in osteoarthritis.

    Science.gov (United States)

    Hunter, D J; Arden, N; Cicuttini, F; Crema, M D; Dardzinski, B; Duryea, J; Guermazi, A; Haugen, I K; Kloppenburg, M; Maheu, E; Miller, C G; Martel-Pelletier, J; Ochoa-Albíztegui, R E; Pelletier, J-P; Peterfy, C; Roemer, F; Gold, G E

    2015-05-01

    Tremendous advances have occurred in our understanding of the pathogenesis of hand osteoarthritis (OA) and these are beginning to be applied to trials targeted at modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply hand imaging assessments in disease modifying clinical trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for MRI); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. Overview of registered studies in orthodontics: Evaluation of the ClinicalTrials.gov registry.

    Science.gov (United States)

    Allareddy, Veerasathpurush; Rampa, Sankeerth; Masoud, Mohamed I; Lee, Min Kyeong; Nalliah, Romesh; Allareddy, Veerajalandhar

    2014-11-01

    The Food and Drug Administration Modernization Act of 1997 made it mandatory for all phase II through IV trials regulated by this Act to be registered. After this, the National Institutes of Health created ClinicalTrials.gov, which is a registry of publicly and privately supported clinical studies of human participants. The objective of this study was to examine the characteristics of registered studies in orthodontics. The ClinicalTrials.gov Web site was used to query all registered orthodontic studies. The search term used was "orthodontics." No limitations were placed for the time period. All registered studies regardless of their recruitment status, study results, and study type were selected for analysis. A total of 64 orthodontic studies were registered as of January 1, 2014. Of these, 52 were interventional, and 12 were observational. Close to 60% of the interventional studies and 66.7% of the observational studies had sample sizes of 50 or fewer subjects. About 21.2% of the interventional studies and 16.7% of the observational studies had sample sizes greater than 100. Only 1 study was funded by the National Institutes of Health, and the rest were funded by "other" or "industry" sources. Close to 87.7% of the interventional studies were randomized. Interventional model assignments included factorial assignment (3.9%), parallel assignments (74.5%), crossover assignment (7.8%), and single-group assignment (13.7%). Most studies were treatment oriented (80.4%). The types of masking used by the interventional studies included open label (28.9%), single blind (44.2%), and double blind (26.9%). Outcome assessors were blinded in only 6 studies. Orthodontic studies registered in ClinicalTrials.gov are dominated by small single-center studies. There are wide variations with regard to treatment allocation approaches and randomization methods in the studies. These results also indicate the need for multicenter clinical studies in orthodontics. Copyright © 2014

  11. 76 FR 9030 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-02-16

    ... Allergy and Infectious Diseases Special Emphasis Panel; Genetics of Lupus. Date: March 11, 2011. Time: 11... Allergy and Infectious Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the Federal... Infectious Diseases Special Emphasis Panel; Ancillary Studies in Immunomodulation Clinical Trials (R01). Date...

  12. Closed cycle gas dynamic laser

    International Nuclear Information System (INIS)

    Pinsley, E.A.

    1975-01-01

    The device includes a closed cycle gasdynamic laser wherein the lasing fluid is recirculated in a closed loop. The closed loop includes a nozzle array, a lasing cavity and a diffuser. The exit of the diffuser is connected to the inlet to the nozzle array with a fuel heat exchanger located in the lasing flow and a pumping means located between the heat exchanger and the nozzle array. To provide for cooling of the pumping means and to improve diffuser performance, gas bled from the diffuser is cooled by two heat exchangers and pumped into cooling passages in the pumping means. The heat exchangers for cooling the flow to the pumping means are located in series and carry fuel from a supply to an injector in said combustor and the heat exchanger in the lasing flow cools the fluid and carries the fuel from a supply to an injector in said combustor. (U.S.)

  13. Asian Americans and Cancer Clinical Trials: A Mixed-Methods Approach to Understanding Awareness and Experience

    Science.gov (United States)

    Paterniti, Debora A.; Chen, Moon S.; Chiechi, Christine; Beckett, Laurel A.; Horan, Nora; Turrell, Corinne; Smith, Ligaya; Morain, Claudia; Montell, Lisa; Gonzalez, Jose Luis; Davis, Sharon; Lara, Primo N.

    2006-01-01

    Cancer clinical trials have been based on low accrual rates. Barriers to recruitment of minority populations affect the generalizability and impact of trial findings for those populations. The authors undertook a mixed-methods approach to understanding levels of awareness and experiences with cancer clinical trials. A survey was administered to new cancer patients and their caretakers (family, close friends, or other social support) at outpatient oncology clinics. Field observations of the trial accrual process also were conducted by employing the grounded theory approach in qualitative methods. Comparison of survey results for Asian-American respondents and non-Asian respondents indicated that Asians were less likely to have heard the term “clinical trial” and were more likely to define a clinical trial as “an experiment” or “a test procedure in a clinic” than non-Asians. Asians were more likely to have employer-based insurance and to report understanding issues related to cost reimbursement. Asians were less likely to have been involved in or to know someone in a trial and reported less willingness than white respondents to consider trial participation. Qualitative observations suggested that Asians who presented for a potential trial were interested in the availability of a novel cancer therapy but were not eligible for available trials. Multiple strategies will be necessary to enhance awareness of and experience with accrual to cancer clinical trials for Asians, including richer understanding and increased involvement of Asians in cancer clinical trials and greater attention to the location and diversity of the Asian population in structuring study centers and evaluating trial results. PMID:16247795

  14. Enhanced clinical-scale manufacturing of TCR transduced T-cells using closed culture system modules.

    Science.gov (United States)

    Jin, Jianjian; Gkitsas, Nikolaos; Fellowes, Vicki S; Ren, Jiaqiang; Feldman, Steven A; Hinrichs, Christian S; Stroncek, David F; Highfill, Steven L

    2018-01-24

    Genetic engineering of T-cells to express specific T cell receptors (TCR) has emerged as a novel strategy to treat various malignancies. More widespread utilization of these types of therapies has been somewhat constrained by the lack of closed culture processes capable of expanding sufficient numbers of T-cells for clinical application. Here, we evaluate a process for robust clinical grade manufacturing of TCR gene engineered T-cells. TCRs that target human papillomavirus E6 and E7 were independently tested. A 21 day process was divided into a transduction phase (7 days) and a rapid expansion phase (14 days). This process was evaluated using two healthy donor samples and four samples obtained from patients with epithelial cancers. The process resulted in ~ 2000-fold increase in viable nucleated cells and high transduction efficiencies (64-92%). At the end of culture, functional assays demonstrated that these cells were potent and specific in their ability to kill tumor cells bearing target and secrete large quantities of interferon and tumor necrosis factor. Both phases of culture were contained within closed or semi-closed modules, which include automated density gradient separation and cell culture bags for the first phase and closed GREX culture devices and wash/concentrate systems for the second phase. Large-scale manufacturing using modular systems and semi-automated devices resulted in highly functional clinical-grade TCR transduced T-cells. This process is now in use in actively accruing clinical trials and the NIH Clinical Center and can be utilized at other cell therapy manufacturing sites that wish to scale-up and optimize their processing using closed systems.

  15. The ACCESS study a Zelen randomised controlled trial of a treatment package including problem solving therapy compared to treatment as usual in people who present to hospital after self-harm: study protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Parag Varsha

    2011-05-01

    Full Text Available Abstract Background People who present to hospital after intentionally harming themselves pose a common and important problem. Previous reviews of interventions have been inconclusive as existing trials have been under powered and done on unrepresentative populations. These reviews have however indicated that problem solving therapy and regular written communications after the self-harm attempt may be an effective treatment. This protocol describes a large pragmatic trial of a package of measures which include problem solving therapy, regular written communication, patient support, cultural assessment, improved access to primary care and a risk management strategy in people who present to hospital after self-harm using a novel design. Methods We propose to use a double consent Zelen design where participants are randomised prior to giving consent to enrol a large representative cohort of patients. The main outcome will be hospital attendance following repetition of self-harm, in the 12 months after recruitment with secondary outcomes of self reported self-harm, hopelessness, anxiety, depression, quality of life, social function and hospital use at three months and one year. Discussion A strength of the study is that it is a pragmatic trial which aims to recruit large numbers and does not exclude people if English is not their first language. A potential limitation is the analysis of the results which is complex and may underestimate any effect if a large number of people refuse their consent in the group randomised to problem solving therapy as they will effectively cross over to the treatment as usual group. However the primary analysis is a true intention to treat analysis of everyone randomised which includes both those who consent and do not consent to participate in the study. This provides information about how the intervention will work in practice in a representative population which is a major advance in this study compared to what has

  16. 78 FR 66946 - National Institute on Deafness and Other Communication Disorders; Notice of Closed Meeting

    Science.gov (United States)

    2013-11-07

    ... Deafness and Other Communication Disorders; Notice of Closed Meeting Pursuant to section 10(d) of the... disclose confidential trade secrets or commercial property such as patentable material, and personal... Deafness and Other Communication Disorders Special Emphasis Panel; Hearing Clinical Trial Review. Date...

  17. 76 FR 12744 - National Institute On Deafness and Other Communication Disorders; Notice of Closed Meetings

    Science.gov (United States)

    2011-03-08

    ... Deafness and Other Communication Disorders; Notice of Closed Meetings Pursuant to section 10(d) of the... Deafness and Other Communication Disorders Special Emphasis Panel; Clinical Trials-- Communications. Date..., [email protected] . Name of Committee: National Institute on Deafness and Other Communication Disorders...

  18. 78 FR 56902 - National Institute on Deafness and Other Communication Disorders; Notice of Closed Meetings

    Science.gov (United States)

    2013-09-16

    ... Deafness and Other Communication Disorders; Notice of Closed Meetings Pursuant to section 10(d) of the... Deafness and Other Communication Disorders Special Emphasis Panel; Vestibular Clinical Trial Review. Date..., Bethesda, MD 20892, (301) 496-8683, [email protected] . Name of Committee: Communication Disorders...

  19. 77 FR 8888 - National Institute on Deafness and Other Communication Disorders; Notice of Closed Meeting

    Science.gov (United States)

    2012-02-15

    ... Deafness and Other Communication Disorders; Notice of Closed Meeting Pursuant to section 10(d) of the... Deafness and Other Communication Disorders Special Emphasis Panel, Clinical Trial Review. Date: February 21.... 93.173, Biological Research Related to Deafness and Communicative Disorders, National Institutes of...

  20. 78 FR 56238 - National Center for Complementary and Alternative Medicine; Notice of Closed Meeting

    Science.gov (United States)

    2013-09-12

    ... Complementary and Alternative Medicine; Notice of Closed Meeting Pursuant to section 10(d) of the Federal... Complementary and Alternative Medicine, National Institutes of Health, HHS) Dated: September 6, 2013. Michelle... Alternative Medicine Special Emphasis Panel; ZAT1 PK28: PAR 10-163 R34 Clinical trial planning grants and...

  1. Algorithms that eliminate the effects of calibration artefact and trial-imposed offsets of Masimo oximeter in BOOST-NZ trial.

    Science.gov (United States)

    Zahari, Marina; Lee, Dominic Savio; Darlow, Brian Alexander

    2016-10-01

    The displayed readings of Masimo pulse oximeters used in the Benefits Of Oxygen Saturation Targeting (BOOST) II and related trials in very preterm babies were influenced by trial-imposed offsets and an artefact in the calibration software. A study was undertaken to implement new algorithms that eliminate the effects of offsets and artefact. In the BOOST-New Zealand trial, oxygen saturations were averaged and stored every 10 s up to 36 weeks' post-menstrual age. Two-hundred and fifty-seven of 340 babies enrolled in the trial had at least two weeks of stored data. Oxygen saturation distribution patterns corresponding with a +3 % or -3 % offset in the 85-95 % range were identified together with that due to the calibration artefact. Algorithms involving linear and quadratic interpolations were developed, implemented on each baby of the dataset and validated using the data of a UK preterm baby, as recorded from Masimo oximeters with the original software and a non-offset Siemens oximeter. Saturation distributions obtained were compared for both groups. There were a flat region at saturations 85-87 % and a peak at 96 % from the lower saturation target oximeters, and at 93-95 and 84 % respectively from the higher saturation target oximeters. The algorithms lowered the peaks and redistributed the accumulated frequencies to the flat regions and artefact at 87-90 %. The resulting distributions were very close to those obtained from the Siemens oximeter. The artefact and offsets of the Masimo oximeter's software had been addressed to determine the true saturation readings through the use of novel algorithms. The implementation would enable New Zealand data be included in the meta-analysis of BOOST II trials, and be used in neonatal oxygen studies.

  2. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    OpenAIRE

    Ghasem Soltani; Mahmood Khorsand; ALireza Sepehri Shamloo; Lida Jarahi; Nahid Zirak

    2015-01-01

    Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They wer...

  3. 76 FR 62423 - National Institute on Deafness and Other Communication Disorders; Notice of Closed Meetings

    Science.gov (United States)

    2011-10-07

    ... Deafness and Other Communication Disorders; Notice of Closed Meetings Pursuant to section 10(d) of the... Deafness and Other Communication Disorders, Special Emphasis Panel, Clinical Trials. Date: October 24, 2011....nih.gov . Name of Committee: National Institute on Deafness and Other Communication Disorders, Special...

  4. 77 FR 35990 - National Institute on Deafness and Other Communication Disorders; Notice of Closed Meetings

    Science.gov (United States)

    2012-06-15

    ... Deafness and Other Communication Disorders; Notice of Closed Meetings Pursuant to section 10(d) of the... Deafness and Other Communication Disorders Special Emphasis Panel; Investigator Initiated R01 Review. Date... Institute on Deafness and Other Communication Disorders Special Emphasis Panel; Clinical Trial Review. Date...

  5. Transparency in ovarian cancer clinical trial results: ClinicalTrials.gov versus PubMed, Embase and Google scholar.

    Science.gov (United States)

    Roberto, Anna; Radrezza, Silvia; Mosconi, Paola

    2018-04-10

    In recent years the question of the lack of transparency in clinical research has been debated by clinicians, researchers, citizens and their representatives, authors and publishers. This is particularly important for infrequent cancers such as ovarian cancer, where treatment still gives disappointing results in the majority of cases. Our aim was to assess the availability to the public of results in ClinicalTrials.gov, and the frequency of non-publication of results in ClinicalTrials.gov and in PubMed, Embase and Google Scholar. We collected all trials on ovarian cancer identified as "completed status" in the ClinicalTrials.gov registry on 17 January 2017. We checked the availability of the results in ClinicalTrials.gov and systematically identified published manuscripts on results. Out of 2725 trials on ovarian cancer identified, 752 were classified as "completed status". In those closed between 2008 and 2015, excluding phase I, the frequency of results in ClinicalTrials.gov was 35%. Of the 752 completed studies the frequency of published results in PubMed, Embase or Google Scholar ranged from 57.9% to 69.7% in the last years. These findings show a lack of transparency and credibility of research. Citizens or patients' representatives, with the medical community, should continuously support initiatives to improve the publication and dissemination of clinical study results.

  6. Effect on attendance by including focused information on spirometry in preventive health checks: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Ørts, Lene Maria; Løkke, Anders; Bjerregaard, Anne-Louise; Maindal, Helle Terkildsen; Sandbæk, Annelli

    2016-12-01

    Early detection of lung diseases can help to reduce their severity. Lung diseases are among the most frequently occurring and serious diseases worldwide; nonetheless, many patients remain undiagnosed. Preventive health checks including spirometry can detect lung diseases at early stages; however, recruitment for health checks remains a challenge, and little is known about what motivates the attendance. The aim of the study is to examine whether focused information on spirometry in the invitation compared to general information will impact the attendance rate in preventive health checks. This randomized, controlled trial tests the effect of information on spirometry embedded in the Check your Health Preventive Program (CHPP). The CHPP is an open-label, household cluster-randomized, controlled trial offering a preventive health check to 30- to -49-year-olds in a Danish municipality from 2012 to 2017 (n = 26,216). During 2015-2016, 4356 citizens aged 30-49 years will be randomized into two groups. The intervention group receives an invitation which highlights the value and contents of spirometry as part of a health check and information about lung diseases. The comparison group receives a standard invitation containing practical information and specifies the contents of the general health check. Outcomes are (1) differences in attendance rates measured by the proportion of citizens attending each of the two study groups and (2) proportion of persons at risk defined by smoking status and self-reported lung symptoms in the study groups. The proportion of participants with abnormal spirometry assessed at the preventive health check will be compared between the two study groups. The results from the present study will inform future recruitment strategies to health checks. The developed material on content, value, and information about lung disease is feasible and transferable to other populations, making it easy to implement if effective. ClinicalTrials.gov: NCT

  7. Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - A position paper endorsed by ESMINT and ESNR. Pt. 2. Methodology of future trials

    Energy Technology Data Exchange (ETDEWEB)

    Fiehler, Jens [University Medical Centre Hamburg-Eppendorf, Department of Neuroradiology, Hamburg (Germany); Soederman, Michael [Karolinska University Hospital, Department of Neuroradiology, Stockholm (Sweden); Turjman, Francis [Hopital neurologique, Centre de Neurosciences Cognitives, Department of Neuroradiology, Lyon (France); White, Philip M. [University of Edinburgh, Department of Clinical Neurosciences, Western General Hospital, Edinburgh (United Kingdom); Bakke, Soeren Jacob [Oslo University Hospital, Department of Neuroradiology, Oslo (Norway); Mangiafico, Salvatore [University Hospital Careggi, Interventional Neuroradiology Unit, Florence (Italy); Kummer, Ruediger von [University of Dresden, Department of Neuroradiology, Dresden (Germany); Muto, Mario [University of Naples, Department of Neuroradiology, Naples (Italy); Cognard, Christophe [Hopital Purpan, Service de Neuroradiologie, Toulouse (France); Gralla, Jan [Inselspital Bern, Department of Neuroradiology, Bern (Switzerland)

    2012-12-15

    Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines. (orig.)

  8. Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - a position paper endorsed by ESMINT and ESNR : part II: methodology of future trials.

    Science.gov (United States)

    Fiehler, Jens; Söderman, Michael; Turjman, Francis; White, Philip M; Bakke, Søren Jacob; Mangiafico, Salvatore; von Kummer, Rüdiger; Muto, Mario; Cognard, Christophe; Gralla, Jan

    2012-12-01

    Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.

  9. Acupuncture for neurological disorders in the Cochrane reviews:Characteristics of included reviews and studies

    Institute of Scientific and Technical Information of China (English)

    Deren Wang; Weimin Yang; Ming Liu

    2011-01-01

    OBJECTIVE: To summarize Cochrane reviews of acupuncture for neurological disorders, and characteristics of included reviews and studies.DATA SOURCES: A computer-based online search of the Cochrane Library (Issue 7 of 12, July 2010) was performed with the key word "acupuncture" and systematic evaluations for acupuncture for neurological disorders were screened.STUDY SELECTION: Systematic reviews on acupuncture in the treatment of neurological disorders were included, and the characteristics of these reviews were analyzed based on methods recommended by the Cochrane collaboration.MAIN OUTCOME MEASURES: Basic characteristics, methodological quality, main reasons for excluding trials, results and conclusions of Cochrane reviews were assessed.RESULTS: A total of 18 Cochrane systematic reviews were included, including 13 completed reviews and five research protocols. The 13 completed reviews involved 111 randomized controlled trials, including 43 trials (38.7%) conducted in China, 47 trials (42.3%) using sham-acupuncture or placebo as control, 15 trials (13.5%) with relatively high quality, 91 trials (81.9%) reporting data on follow-up. Primary outcomes used in the Cochrane reviews were reported by 65 trials (58.6%), and adverse events were reported in 11 trials (9.9%). Two hundred and eighty three trials were excluded. Two reviews on headache suggested that acupuncture is a valuable non-drug treatment for patients with chronic or recurrent headache, and has better curative effects on migraine compared with preventative drug treatment. CONCLUSION: Of the Cochrane reviews on acupuncture in the treatment of neurological disorders, two reviews evaluating the efficacy of acupuncture in treating headaches drew positive conculsions, while other reviews did not obtain positive conclusions due to a small sample size or low methodological quality. The methodological quality of acupuncture trials needs further improvement.

  10. Non-metric close range photogrammetric system for mapping geologic structures in mines

    Energy Technology Data Exchange (ETDEWEB)

    Brandow, V D

    1976-01-01

    A stereographic close-range photogrammetric method of obtaining structural data for mine roof stability analyses is described. Stereo pairs were taken with 70 mm and 35 mm non-metric cameras. Photo co-ordinates were measured with a stereo-comparator and reduced by the direct linear transformation method. Field trials demonstrate that the technique is sufficiently accurate for geological work and is a practical method of mapping.

  11. Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID: protocol for a randomized clinical multi-center trial

    Directory of Open Access Journals (Sweden)

    Seiler Christoph

    2011-03-01

    Full Text Available Abstract Background Fractures of the distal radius represent the most common fracture in elderly patients, and often indicate the onset of symptomatic osteoporosis. A variety of treatment options is available, including closed reduction and plaster casting, K-wire-stabilization, external fixation and open reduction and internal fixation (ORIF with volar locked plating. The latter is widely promoted by clinicians and hardware manufacturers. Closed reduction and cast stabilization for six weeks is a simple, convenient, and ubiquitously available intervention. In contrast, ORIF requires hospitalization, but allows for functional rehabilitation. Given the lack of randomized controlled trials, it remains unclear whether ORIF leads to better functional outcomes one year after injury than closed reduction and casting. Methods/Design ORCHID (Open reduction and internal fixation versus casting for highly comminuted intra-articular fractures of the distal radius is a pragmatic, randomized, multi-center, clinical trial with two parallel treatment arms. It is planned to include 504 patients in 15 participating centers throughout Germany over a three-year period. Patients are allocated by a central web-based randomization tool. The primary objective is to determine differences in the Short Form 36 (SF-36 Physical Component Score (PCS between volar locked plating and closed reduction and casting of intraarticular, comminuted distal radius fractures in patients > 65 years of age one year after the fracture. Secondary outcomes include differences in other SF-36 dimensions, the EuroQol-5D questionnaire, the Disability of the Arm, Shoulder, and Hand (DASH instrument. Also, the range of motion in the affected wrist, activities of daily living, complications (including secondary ORIF and revision surgery, as well as serious adverse events will be assessed. Data obtained during the trial will be used for later health-economic evaluations. The trial architecture

  12. Home medicines reviews following acute coronary syndrome: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Bernal Daniel DL

    2012-04-01

    Full Text Available Abstract Background Despite continual improvements in the management of acute coronary syndromes, adherence to guideline-based medications remains suboptimal. We aim to improve adherence with guideline-based therapy following acute coronary syndrome using an existing service that is provided by specifically trained pharmacists, called a Home Medicines Review. We have made two minor adjustments to target the focus of the existing service including an acute coronary syndrome specific referral letter and a training package for the pharmacists providing the service. Methods/Design We will be conducting a randomized controlled trial to compare the directed home medicines review service to usual care following acute coronary syndromes. All patients aged 18 to 80 years and with a working diagnosis of acute coronary syndrome, who are admitted to two public, acute care hospitals, will be screened for enrolment into the trial. Exclusion criteria will include: not being discharged home, documented cognitive decline, non-Medicare eligibility, and presence of a terminal malignancy. Randomization concealment and sequence generation will occur through a centrally-monitored computer program. Patients randomized to the control group will receive usual post-discharge care. Patients randomized to receive the intervention will be offered usual post-discharge care and a directed home medicines review at two months post-discharge. The study endpoints will be six and twelve months post-discharge. The primary outcome will be the proportion of patients who are adherent to a complete, guideline-based medication regimen. Secondary outcomes will include hospital readmission rates, length of hospital stays, changes in quality of life, smoking cessation rates, cardiac rehabilitation completion rates, and mortality. Discussion As the trial is closely based on an existing service, any improvements observed should be highly translatable into regular practice. Possible

  13. Research Areas - Clinical Trials

    Science.gov (United States)

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  14. Pipeline Decommissioning Trial AWE Berkshire UK - 13619

    Energy Technology Data Exchange (ETDEWEB)

    Agnew, Kieran [AWE, Aldermaston, Reading, RG7 4PR (United Kingdom)

    2013-07-01

    This Paper details the implementation of a 'Decommissioning Trial' to assess the feasibility of decommissioning the redundant pipeline operated by AWE located in Berkshire UK. The paper also presents the tool box of decommissioning techniques that were developed during the decommissioning trial. Constructed in the 1950's and operated until 2005, AWE used a pipeline for the authorised discharge of treated effluent. Now redundant, the pipeline is under a care and surveillance regime awaiting decommissioning. The pipeline is some 18.5 km in length and extends from AWE site to the River Thames. Along its route the pipeline passes along and under several major roads, railway lines and rivers as well as travelling through woodland, agricultural land and residential areas. Currently under care and surveillance AWE is considering a number of options for decommissioning the pipeline. One option is to remove the pipeline. In order to assist option evaluation and assess the feasibility of removing the pipeline a decommissioning trial was undertaken and sections of the pipeline were removed within the AWE site. The objectives of the decommissioning trial were to: - Demonstrate to stakeholders that the pipeline can be removed safely, securely and cleanly - Develop a 'tool box' of methods that could be deployed to remove the pipeline - Replicate the conditions and environments encountered along the route of the pipeline The onsite trial was also designed to replicate the physical prevailing conditions and constraints encountered along the remainder of its route i.e. working along a narrow corridor, working in close proximity to roads, working in proximity to above ground and underground services (e.g. Gas, Water, Electricity). By undertaking the decommissioning trial AWE have successfully demonstrated the pipeline can be decommissioned in a safe, secure and clean manor and have developed a tool box of decommissioning techniques. The tool box of includes

  15. Including pork in the Mediterranean diet for an Australian population: Protocol for a randomised controlled trial assessing cardiovascular risk and cognitive function.

    Science.gov (United States)

    Wade, Alexandra T; Davis, Courtney R; Dyer, Kathryn A; Hodgson, Jonathan M; Woodman, Richard J; Keage, Hannah A D; Murphy, Karen J

    2017-12-22

    The Mediterranean diet is characterised by the high consumption of extra virgin olive oil, fruits, vegetables, grains, legumes and nuts; moderate consumption of fish, poultry, eggs and dairy; and low consumption of red meat and sweets. Cross sectional, longitudinal and intervention studies indicate that a Mediterranean diet may be effective for the prevention of cardiovascular disease and dementia. However, previous research suggests that an Australian population may find red meat restrictions difficult, which could affect long term sustainability of the diet. This paper outlines the protocol for a randomised controlled trial that will assess the cardiovascular and cognitive benefits of a Mediterranean diet modified to include 2-3 weekly serves of fresh, lean pork. A 24-week cross-over design trial will compare a modified Mediterranean diet with a low-fat control diet in at-risk men and women. Participants will follow each of the two diets for 8 weeks, with an 8-week washout period separating interventions. Home measured systolic blood pressure will be the primary outcome measure. Secondary outcomes will include body mass index, body composition, fasting blood lipids, C-reactive protein, fasting plasma glucose, fasting serum insulin, erythrocyte fatty acids, cognitive function, psychological health and well-being, and dementia risk. To our knowledge this research is the first to investigate whether an alternate source of protein can be included in the Mediterranean diet to increase sustainability and feasibility for a non-Mediterranean population. Findings will be significant for the prevention of cardiovascular disease and age-related decline, and may inform individuals, clinicians and public health policy. ACTRN12616001046493 . Registered 5 August 2016.

  16. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression.

    Science.gov (United States)

    Widge, Alik S; Malone, Donald A; Dougherty, Darin D

    2018-01-01

    Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial "failures" are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this "valley of disillusionment," DBS may be nearing a "slope of enlightenment." Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

  17. Efficacy of physiotherapy including a craniocervical training programme for tension-type headache; a randomized clinical trial

    NARCIS (Netherlands)

    van Ettekoven, H.; Lucas, C.

    2006-01-01

    We conducted a multicentre, randomized controlled trial with blinded outcome assessment. The treatment period was 6 weeks with follow-up assessment immediately thereafter and after 6 months. The objective was to determine the effectiveness of a craniocervical training programme combined with

  18. A comparison of different ways of including baseline counts in negative binomial models for data from falls prevention trials.

    Science.gov (United States)

    Zheng, Han; Kimber, Alan; Goodwin, Victoria A; Pickering, Ruth M

    2018-01-01

    A common design for a falls prevention trial is to assess falling at baseline, randomize participants into an intervention or control group, and ask them to record the number of falls they experience during a follow-up period of time. This paper addresses how best to include the baseline count in the analysis of the follow-up count of falls in negative binomial (NB) regression. We examine the performance of various approaches in simulated datasets where both counts are generated from a mixed Poisson distribution with shared random subject effect. Including the baseline count after log-transformation as a regressor in NB regression (NB-logged) or as an offset (NB-offset) resulted in greater power than including the untransformed baseline count (NB-unlogged). Cook and Wei's conditional negative binomial (CNB) model replicates the underlying process generating the data. In our motivating dataset, a statistically significant intervention effect resulted from the NB-logged, NB-offset, and CNB models, but not from NB-unlogged, and large, outlying baseline counts were overly influential in NB-unlogged but not in NB-logged. We conclude that there is little to lose by including the log-transformed baseline count in standard NB regression compared to CNB for moderate to larger sized datasets. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID): protocol for a randomized clinical multi-center trial.

    Science.gov (United States)

    Bartl, Christoph; Stengel, Dirk; Bruckner, Thomas; Rossion, Inga; Luntz, Steffen; Seiler, Christoph; Gebhard, Florian

    2011-03-22

    Fractures of the distal radius represent the most common fracture in elderly patients, and often indicate the onset of symptomatic osteoporosis. A variety of treatment options is available, including closed reduction and plaster casting, K-wire-stabilization, external fixation and open reduction and internal fixation (ORIF) with volar locked plating. The latter is widely promoted by clinicians and hardware manufacturers. Closed reduction and cast stabilization for six weeks is a simple, convenient, and ubiquitously available intervention. In contrast, ORIF requires hospitalization, but allows for functional rehabilitation.Given the lack of randomized controlled trials, it remains unclear whether ORIF leads to better functional outcomes one year after injury than closed reduction and casting. ORCHID (Open reduction and internal fixation versus casting for highly comminuted intra-articular fractures of the distal radius) is a pragmatic, randomized, multi-center, clinical trial with two parallel treatment arms. It is planned to include 504 patients in 15 participating centers throughout Germany over a three-year period. Patients are allocated by a central web-based randomization tool.The primary objective is to determine differences in the Short Form 36 (SF-36) Physical Component Score (PCS) between volar locked plating and closed reduction and casting of intraarticular, comminuted distal radius fractures in patients > 65 years of age one year after the fracture. Secondary outcomes include differences in other SF-36 dimensions, the EuroQol-5D questionnaire, the Disability of the Arm, Shoulder, and Hand (DASH) instrument. Also, the range of motion in the affected wrist, activities of daily living, complications (including secondary ORIF and revision surgery), as well as serious adverse events will be assessed. Data obtained during the trial will be used for later health-economic evaluations. The trial architecture involves a central statistical unit, an independent

  20. Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.

    Science.gov (United States)

    Paoletti, X; Ezzalfani, M; Le Tourneau, C

    2015-09-01

    More than 95% of published phase I trials have used the 3 + 3 design to identify the dose to be recommended for phase II trials. However, the statistical community agrees on the limitations of the 3 + 3 design compared with model-based approaches. Moreover, the mechanisms of action of targeted agents strongly challenge the hypothesis that the maximum tolerated dose constitutes the optimal dose, and more outcomes including clinical and biological activity increasingly need to be taken into account to identify the optimal dose. We review key elements from clinical publications and from the statistical literature to show that the 3 + 3 design lacks the necessary flexibility to address the challenges of targeted agents. The design issues raised by expansion cohorts, new definitions of dose-limiting toxicity and trials of combinations are not easily addressed by the 3 + 3 design or its extensions. Alternative statistical proposals have been developed to make a better use of the complex data generated by phase I trials. Their applications require a close collaboration between all actors of early phase clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. A constitutive model for the compressive response of metallic closed-cell foams including micro-inertia effects

    Directory of Open Access Journals (Sweden)

    Barthélémy Romain

    2015-01-01

    Full Text Available Metallic foams have known a keen interest in the last decades. Their ability to undergo very large deformations while transmitting low stress levels make them capable of performing functions of protective layers against intense loadings and of energy absorbers, for instance. The behaviour of metal foams varies considerably between quasi-static and dynamic regimes. Those differences can be linked to the strain-rate sensitivity of the skeleton material and to micro-inertial effects (induced by the crushing of the foam cells. In the present work, a micromechanical model has been developed to take into account micro-inertia effects on the macroscopic behaviour of closed-cell foams under dynamic loading conditions. The proposed modelling is based on the dynamic homogenisation procedure introduced by Molinari and Mercier (J. Mech. Phys. Solids 49 (2001 1497–1516. Within this framework, the macrostress is the sum of two terms. The first one is a static stress, that can be described with any existing model of metal foam. The second contribution is a dynamic stress related to micro-inertia effects. Considering an initially spherical shell as a Representative Volume Element (RVE of the foam material, a closed-form expression of the dynamic stress was obtained. The proposed modelling was applied to shock propagation in aluminium foams (it should however be noted that the present theory is not restricted to uniaxial deformation but can be applied to arbitrary loadings. From experimental data of the literature, it is observed that incorporating micro-inertia effects allows one to achieve a better description of the foam shock response. This indicates that micro-inertia may have a significant influence on the dynamic behaviour of metallic foams.

  2. Making co-enrolment feasible for randomised controlled trials in paediatric intensive care.

    Directory of Open Access Journals (Sweden)

    Katie Harron

    Full Text Available Enrolling children into several trials could increase recruitment and lead to quicker delivery of optimal care in paediatric intensive care units (PICU. We evaluated decisions taken by clinicians and parents in PICU on co-enrolment for two large pragmatic trials: the CATCH trial (CATheters in CHildren comparing impregnated with standard central venous catheters (CVCs for reducing bloodstream infection in PICU and the CHIP trial comparing tight versus standard control of hyperglycaemia.We recorded the period of trial overlap for all PICUs taking part in both CATCH and CHiP and reasons why clinicians decided to co-enrol children or not into both studies. We examined parental decisions on co-enrolment by measuring recruitment rates and reasons for declining consent.Five PICUs recruited for CATCH and CHiP during the same period (an additional four opened CATCH after having closed CHiP. Of these five, three declined co-enrolment (one of which delayed recruiting elective patients for CATCH whilst CHiP was running, due to concerns about jeopardising CHiP recruitment, asking too much of parents, overwhelming amounts of information to explain to parents for two trials and a policy against co-enrolment. Two units co-enrolled in order to maximise recruitment to both trials. At the first unit, 35 parents were approached for both trials. 17/35 consented to both; 13/35 consented to one trial only; 5/35 declined both. Consent rates during co-enrolment were 29/35 (82% and 18/35 (51% for CATCH and CHiP respectively compared with 78% and 51% respectively for those approached for a single trial within this PICU. The second unit did not record data on approaches or refusals, but successfully co-enrolled one child.Co-enrolment did not appear to jeopardise recruitment or overwhelm parents. Strategies for seeking consent for multiple trials need to be developed and should include how to combine information for parents and patients.

  3. Key ecological challenges for closed systems facilities

    Science.gov (United States)

    Nelson, Mark; Dempster, William F.; Allen, John P.

    2013-07-01

    Closed ecological systems are desirable for a number of purposes. In space life support systems, material closure allows precious life-supporting resources to be kept inside and recycled. Closure in small biospheric systems facilitates detailed measurement of global ecological processes and biogeochemical cycles. Closed testbeds facilitate research topics which require isolation from the outside (e.g. genetically modified organisms; radioisotopes) so their ecological interactions and fluxes can be studied separate from interactions with the outside environment. But to achieve and maintain closure entails solving complex ecological challenges. These challenges include being able to handle faster cycling rates and accentuated daily and seasonal fluxes of critical life elements such as carbon dioxide, oxygen, water, macro- and mico-nutrients. The problems of achieving sustainability in closed systems for life support include how to handle atmospheric dynamics including trace gases, producing a complete human diet, recycling nutrients and maintaining soil fertility, the maintenance of healthy air and water and preventing the loss of critical elements from active circulation. In biospheric facilities, the challenge is also to produce analogues to natural biomes and ecosystems, studying processes of self-organization and adaptation in systems that allow specification or determination of state variables and cycles which may be followed through all interactions from atmosphere to soils. Other challenges include the dynamics and genetics of small populations, the psychological challenges for small isolated human groups and backup technologies and strategic options which may be necessary to ensure long-term operation of closed ecological systems.

  4. On H-closed and U-closed functions | Cammaroto | Quaestiones ...

    African Journals Online (AJOL)

    In this article, we extend the work on H-closed functions started by Cammaroto, Fedorchuk and Porter in 1998. Also, U-closed functions are introduced and characterized in terms of filters and adherence. The hereditary and productivity properties are examined and developed for both H-closed and U-closed functions.

  5. Complete blood count risk score and its components, including RDW, are associated with mortality in the JUPITER trial.

    Science.gov (United States)

    Horne, Benjamin D; Anderson, Jeffrey L; Muhlestein, Joseph B; Ridker, Paul M; Paynter, Nina P

    2015-04-01

    Previously, we showed that sex-specific complete blood count (CBC) risk scores strongly predicted risk of all-cause mortality in multiple sets of general medical patients. This study evaluated the CBC risk score in an independent, well-studied international primary risk population of lower-risk individuals initially free from cardiovascular (CV) disease. Observational secondary analysis of a randomized trial population. The previously derived and validated CBC score was evaluated for association with all-cause mortality among CV disease-free females (n = 6568) and males (n = 10,629) enrolled for up to 5 years in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Associations of the CBC score with CV mortality and with major CV disease were also tested. The CBC score predicted all-cause mortality, with univariable hazard ratio (HR) 4.83 (95% CI 3.70-6.31) for the third CBC score tertile vs. the first tertile, and HR 2.31 (CI 1.75-3.05) for the second tertile (p trend JUPITER endpoint (p trend = 0.015). c-statistics for mortality were 0.729 among all, and 0.722 and 0.750 for females and males, respectively. The CBC risk score was strongly associated with all-cause mortality among JUPITER trial participants and had good discrimination. It also predicted CV-specific outcomes. This CBC score may be useful in identifying cardiac disease-free individuals at increased risk of mortality. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

    Science.gov (United States)

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

    2008-12-01

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

  7. Predictive probability methods for interim monitoring in clinical trials with longitudinal outcomes.

    Science.gov (United States)

    Zhou, Ming; Tang, Qi; Lang, Lixin; Xing, Jun; Tatsuoka, Kay

    2018-04-17

    In clinical research and development, interim monitoring is critical for better decision-making and minimizing the risk of exposing patients to possible ineffective therapies. For interim futility or efficacy monitoring, predictive probability methods are widely adopted in practice. Those methods have been well studied for univariate variables. However, for longitudinal studies, predictive probability methods using univariate information from only completers may not be most efficient, and data from on-going subjects can be utilized to improve efficiency. On the other hand, leveraging information from on-going subjects could allow an interim analysis to be potentially conducted once a sufficient number of subjects reach an earlier time point. For longitudinal outcomes, we derive closed-form formulas for predictive probabilities, including Bayesian predictive probability, predictive power, and conditional power and also give closed-form solutions for predictive probability of success in a future trial and the predictive probability of success of the best dose. When predictive probabilities are used for interim monitoring, we study their distributions and discuss their analytical cutoff values or stopping boundaries that have desired operating characteristics. We show that predictive probabilities utilizing all longitudinal information are more efficient for interim monitoring than that using information from completers only. To illustrate their practical application for longitudinal data, we analyze 2 real data examples from clinical trials. Copyright © 2018 John Wiley & Sons, Ltd.

  8. A prospective, randomised trial comparing closed intramedullary nailing with percutaneous plating in the treatment of distal metaphyseal fractures of the tibia.

    Science.gov (United States)

    Guo, J J; Tang, N; Yang, H L; Tang, T S

    2010-07-01

    We compared the outcome of closed intramedullary nailing with minimally invasive plate osteosynthesis using a percutaneous locked compression plate in patients with a distal metaphyseal fracture in a prospective study. A total of 85 patients were randomised to operative stabilisation either by a closed intramedullary nail (44) or by minimally invasive osteosynthesis with a compression plate (41). Pre-operative variables included the patients' age and the side and pattern of the fracture. Peri-operative variables were the operating time and the radiation time. Postoperative variables were wound problems, the time to union of the fracture, the functional American Orthopaedic Foot and Ankle surgery score and removal of hardware. We found no significant difference in the pre-operative variables or in the time to union in the two groups. However, the mean radiation time and operating time were significantly longer in the locked compression plate group (3.0 vs 2.12 minutes, p fractures had united. Patients who had intramedullary nailing had a higher mean pain score (40 = no pain, 0 = severe pain), [corrected] but better function, alignment and total American Orthopaedic Foot and Ankle surgery scores, although the differences were not statistically significant (p = 0.234, p = 0.157, p = 0.897, p = 0.177 respectively). Three (6.8%) patients in the intramedullary nailing group and six (14.6%) in the locked compression plate group showed delayed wound healing, and 37 (84.1%) in the former group and 38 (92.7%) in the latter group expressed a wish to have the implant removed. We conclude that both closed intramedullary nailing and a percutaneous locked compression plate can be used safely to treat Orthopaedic Trauma Association type-43A distal metaphyseal fractures of the tibia. However, closed intramedullary nailing has the advantage of a shorter operating and radiation time and easier removal of the implant. We therefore prefer closed intramedullary nailing for patients with

  9. Closed hollow bulb obturator--one-step fabrication: a clinical report.

    Science.gov (United States)

    Buzayan, Muaiyed M; Ariffin, Yusnidar T; Yunus, Norsiah

    2013-10-01

    A method is described for the fabrication of a closed hollow bulb obturator prosthesis using a hard thermoforming splint material and heat-cured acrylic resin. The technique allowed the thickness of the thermoformed bulb to be optimized for weight reduction, while the autopolymerized seal area was covered in heat-cured acrylic resin, thus eliminating potential leakage and discoloration. This technique permits the obturator prosthesis to be processed to completion from the wax trial denture without additional laboratory investing, flasking, and processing. © 2013 by the American College of Prosthodontists.

  10. "It Is Definitely a Game Changer": A Qualitative Study of Experiences with In-home Overnight Closed-Loop Technology Among Adults with Type 1 Diabetes.

    Science.gov (United States)

    Hendrieckx, Christel; Poole, Lucinda A; Sharifi, Amin; Jayawardene, Dilshani; Loh, Margaret M; Horsburgh, Jodie C; Bach, Leon A; Colman, Peter G; Kumareswaran, Kavita; Jenkins, Alicia J; MacIsaac, Richard J; Ward, Glenn M; Grosman, Benyamin; Roy, Anirban; O'Neal, David N; Speight, Jane

    2017-07-01

    This qualitative study explored trial participants' experiences of four nights of in-home closed loop. Sixteen adults with type 1 diabetes, who completed a randomized crossover trial, were interviewed after four consecutive nights of closed-loop. Interviews were audio recorded, transcribed, and analyzed with a coding framework developed to identify the main themes. Participants had a mean age of 42 ± 10 years, nine were women; mean diabetes duration was 27 ± 7 years, and all were using insulin pumps. Overall, first impressions were positive. Participants found closed-loop easy to use and understand. Most experienced more stable overnight glucose levels, although for some these were similar to usual care or higher than they expected. Compared with their usual treatment, they noticed the proactive nature of the closed-loop, being able to predict trends and deliver micro amounts of insulin. Most reported technical glitches or inconveniences during one or more nights, such as transmission problems, problematic connectivity between devices, ongoing alarms despite addressing low glucose levels, and sensor inaccuracy. Remote monitoring by the trial team and their own hypoglycemic awareness contributed to feelings of trust and safety. Although rare, safety concerns were raised, related to feeling unsure whether the system would respond in time to falling glucose levels. This study provides relevant insights for implementation of closed-loop in the real world. For people with diabetes who are less familiar with technology, remote monitoring for the first few days may provide reassurance, strengthen their trust/skills, and make closed-loop an acceptable option for more people with type 1 diabetes.

  11. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

    Directory of Open Access Journals (Sweden)

    Alik S. Widge

    2018-03-01

    Full Text Available Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI, the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

  12. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

    Science.gov (United States)

    Widge, Alik S.; Malone, Donald A.; Dougherty, Darin D.

    2018-01-01

    Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care. PMID:29618967

  13. 76 FR 36554 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2011-06-22

    ... Special Emphasis Panel, Feasibility Studies for Clinical Trials in Type 1 Diabetes. Date: July 18, 2011..., 2011. Time: 1 to 5 p.m. Agenda: To review and evaluate grant applications. Place: National Institutes... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the...

  14. Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

    Science.gov (United States)

    Kramer, George C.; Wade, Charles E.; Dubick, Michael A.; Atkins, James L.

    2004-01-01

    Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure surgery. HSD and HSS have received regulatory approval in 14 and 3 countries, respectively, with 81,000+ units sold. The primary reported use was head injury and trauma resuscitation. Complications and reported adverse events are surprisingly rare and not significantly different from other solutions.HBOCs are potent volume expanders in addition to oxygen carriers with volume expansion greater than standard colloids. Several investigators have evaluated small volume hyperoncotic HBOCs or HS-HBOC formulations for hypotensive and normotensive resuscitation in animals. A consistent finding in resuscitation with HBOCs is depressed cardiac output. There is some evidence that HBOCs more efficiently unload oxygen from plasma hemoglobin as well as facilitate RBC

  15. Randomized controlled trial of bipolar diathermy vs ultrasonic scalpel for closed hemorrhoidectomy

    Science.gov (United States)

    Tsunoda, Akira; Sada, Haruki; Sugimoto, Takuya; Kano, Nobuyasu; Kawana, Mariko; Sasaki, Tadanori; Hashimoto, Hideki

    2011-01-01

    AIM: To compare hemorrhoidectomy with a bipolar electrothermal device or hemorrhoidectomy using an ultrasonically activated scalpel. METHODS: Sixty patients with grade III or IV hemorrhoids were prospectively randomized to undergo closed hemorrhoidectomy assisted by bipolar diathermy (group 1) or hemorrhoidectomy with the ultrasonic scalpel (group 2). Operative data were recorded, and patients were followed at 1, 3, and 6 wk to evaluate complications. Independent assessors were assigned to obtain postoperative pain scores, oral analgesic requirement and satisfaction scores. RESULTS: Reduced intraoperative blood loss median 0.9 mL (95% CI: 0.8-3.7) vs 4.6 mL (95% CI: 3.8-7.0), P = 0.001 and a short operating time median 16 (95% CI: 14.6-18.2) min vs 31 (95% CI: 28.1-35.3) min, P < 0.0001 was observed in group 1 compared with group 2. There was a trend towards lower postoperative pain scores on day 1 group 1 median 2 (95% CI: 1.8-3.5) vs group 2 median 3 (95% CI: 2.6-4.2), P = 0.135. Reduced oral analgesic requirement during postoperative 24 h after operation median 1 (95% CI: 0.4-0.9) tablet vs 1 (95% CI: 0.9-1.3) tablet, P = 0.006 was observed in group 1 compared with group 2. There was no difference between the two groups in the degree of patient satisfaction or number of postoperative complications. CONCLUSION: Bipolar diathermy hemorrhoidectomy is quick and bloodless and, although as painful as closed hemorrhoidectomy with the ultrasonic scalpel, is associated with a reduced analgesic requirement immediately after operation. PMID:22110846

  16. UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

    Science.gov (United States)

    Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

    2012-04-28

    Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and

  17. Update on TROG trials

    International Nuclear Information System (INIS)

    Joseph, D.

    2001-01-01

    Full text: Validation of treatment methodologies can only be achieved in the context of unambiguous, efficiently managed, randomised and controlled clinical trials. Since 1991, the Trans-Tasman Radiation Oncology Group (TROG) has coordinated over 29 protocols in radiation oncology, including several key randomised controlled trials. The impetus behind TROG is the establishment of an evidence base for particular approaches to radiotherapy and its adjunct use with alternative and complementary treatment methods. As the level of technology incorporated into radiotherapy continues to increase, as the need for improved accuracy in dose assessment increases and as the requirements of realistic quality assurance (QA) for clinical trials becomes more demanding it is imperative that all professionals involved in radiotherapy, including physicists, become actively involved in the QA of trials. This is particularly important for large scale multi-centre trials which intend to prove the benefits of particular treatment approaches on a national or international stage rather then in the context of a single clinic. This talk will: 1. Examine the outcomes of TROG trials to date in terms of the information obtained. 2. Briefly consider current and impending TROG trials and their requirements in terms of clinical and physics input. 3. Examine the results of international clinical trials in terms of the influence they have had on radiotherapy practice and health outcomes, and the advantages they have obtained by consistent co-operation between clinical and technological staff. 4. Consider the benefits of multi-centre clinical trials and the QA controls that are necessary to ensure accuracy of resulting recommendations. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

  18. Close Contact Casting vs Surgery for Initial Treatment of Unstable Ankle Fractures in Older Adults: A Randomized Clinical Trial.

    Science.gov (United States)

    Willett, Keith; Keene, David J; Mistry, Dipesh; Nam, Julian; Tutton, Elizabeth; Handley, Robert; Morgan, Lesley; Roberts, Emma; Briggs, Andrew; Lall, Ranjit; Chesser, Timothy J S; Pallister, Ian; Lamb, Sarah E

    2016-10-11

    Ankle fractures cause substantial morbidity in older persons. Surgical fixation is the contemporary intervention but is associated with infection and other healing complications. To determine whether initial fracture treatment with close contact casting, a molded below-knee cast with minimal padding, offers outcome equivalent to that with immediate surgery, with fewer complications and less health resource use. This was a pragmatic, equivalence, randomized clinical trial with blinded outcome assessors. A pilot study commenced in May 2004, followed by multicenter recruitment from July 2010 to November 2013; follow-up was completed May 2014. Recruitment was from 24 UK major trauma centers and general hospitals. Participants were 620 adults older than 60 years with acute, overtly unstable ankle fracture. Exclusions were serious limb or concomitant disease or substantial cognitive impairment. Participants were randomly assigned to surgery (n = 309) or casting (n = 311). Casts were applied in the operating room under general or spinal anesthesia by a trained surgeon. The primary 6-month, per-protocol outcome was the Olerud-Molander Ankle Score at 6 months (OMAS; range, 0-100; higher scores indicate better outcomes and fewer symptoms), equivalence prespecified as ±6 points. Secondary outcomes were quality of life, pain, ankle motion, mobility, complications, health resource use, and patient satisfaction. Among 620 adults (mean age, 71 years; 460 [74%] women) who were randomized, 593 (96%) completed the study. Nearly all participants (579/620; 93%) received allocated treatment; 52 of 275 (19%) who initially received casting later converted to surgery, which was allowable in the casting treatment pathway to manage early loss of fracture reduction. At 6 months, casting resulted in ankle function equivalent to that with surgery (OMAS score, 66.0 [95% CI, 63.6-68.5] for surgery vs 64.5 [95% CI, 61.8-67.2] for casting; mean difference, -0.6 [95% CI, -3.9 to 2.6]; P

  19. 75 FR 34462 - Eunice Kennedy Shriver National Institute of Child Health and Human Development; Notice of Closed...

    Science.gov (United States)

    2010-06-17

    ... Institute of Child Health and Human Development Special Emphasis Panel; Adolescent Medicine Trials Network... National Institute of Child Health and Human Development; Notice of Closed Meeting Pursuant to section 10(d..., National Institute of Child Health and Human Development, NIH, 6100 Executive Blvd. Room 5b01, Bethesda, MD...

  20. Mappings with closed range and compactness

    International Nuclear Information System (INIS)

    Iyahen, S.O.; Umweni, I.

    1985-12-01

    The motivation for this note is the result of E.O. Thorp that a normed linear space E is finite dimensional if and only if every continuous linear map for E into any normed linear space has a closed range. Here, a class of Hausdorff topological groups is introduced; called r-compactifiable topological groups, they include compact groups, locally compact Abelian groups and locally convex linear topological spaces. It is proved that a group in this class which is separable, complete metrizable or locally compact, is necessarily compact if its image by a continuous group homomorphism is necessarily closed. It is deduced then that a Hausdorff locally convex is zero if its image by a continuous additive map is necessarily closed. (author)

  1. Is investigator background related to outcome in head to head trials of psychotherapy and pharmacotherapy for adult depression? A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ioana A Cristea

    Full Text Available The influence of factors related to the background of investigators conducting trials comparing psychotherapy and pharmacotherapy has remained largely unstudied. Specializations emphasizing biological determinants of mental disorders, like psychiatry, might favor pharmacotherapy, while others stressing psychosocial factors, like psychology, could promote psychotherapy. Yet financial conflict of interest (COI could be a confounding factor as authors with a medical specialization might receive more sponsoring from the pharmaceutical industry.We conducted a meta-analysis with subgroup and meta-regression analysis examining whether the specialization and affiliation of trial authors were associated to outcomes in the direct comparison of psychotherapy and pharmacotherapy for the acute treatment of depression. Meta-regression analysis also included trial risk of bias and author conflict of interest in relationship to the pharmaceutical industry.We included 45 trials. In half, the first author was psychologist. The last author was psychiatrist/MD in half of the trials, and a psychologist or statistician/other technical in the rest. Most lead authors had medical affiliations. Subgroup analysis indicated that studies with last authors statisticians favored pharmacotherapy. Univariate analysis showed a negative relationship between the presence of statisticians and outcomes favoring psychotherapy. Multivariate analysis showed that trials including authors with financial COI reported findings more favorable to pharmacotherapy.We report the first detailed overview of the background of authors conducting head to head trials for depression. Trials co-authored by statisticians appear to subtly favor pharmacotherapy. Receiving funding from the industry is more closely related to finding better outcomes for the industry's elective treatment than are factors related to authors' background.For a minority of authors we could not retrieve background information

  2. Close Air Support in a Joint Environment: Disconnect Between the Services and How Can Close Air Support Be Improved

    Science.gov (United States)

    2013-04-05

    military expecting technology to close the gap between the lack of CAS training and the expected pilot proficiency in multiple roles? To be an... Research Project. Carlisle Barracks: U.S. Army War College, 19 March 2004. McGrath, John. Fire for Effect: Field Artillery and Close Air Support in...including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations

  3. 77 FR 36564 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-06-19

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Clinical Trial Planning Grants in Type 1 Diabetes. Date: July 12, 2012. Time: 4:00 p.m. to 5:30 p.m. Agenda: To review and evaluate grant... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the...

  4. Fundamentals of clinical trials

    CERN Document Server

    Friedman, Lawrence M; DeMets, David L; Reboussin, David M; Granger, Christopher B

    2015-01-01

    This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise.  Most chapters have been revised considerably from the fourth edition.  A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded.  Many contemporary clinical trial examples have been added.  There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing, and international trials.  This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of ...

  5. Graph topologies on closed multifunctions

    Directory of Open Access Journals (Sweden)

    Giuseppe Di Maio

    2003-10-01

    Full Text Available In this paper we study function space topologies on closed multifunctions, i.e. closed relations on X x Y using various hypertopologies. The hypertopologies are in essence, graph topologies i.e topologies on functions considered as graphs which are subsets of X x Y . We also study several topologies, including one that is derived from the Attouch-Wets filter on the range. We state embedding theorems which enable us to generalize and prove some recent results in the literature with the use of known results in the hyperspace of the range space and in the function space topologies of ordinary functions.

  6. Describing qualitative research undertaken with randomised controlled trials in grant proposals: a documentary analysis.

    Science.gov (United States)

    Drabble, Sarah J; O'Cathain, Alicia; Thomas, Kate J; Rudolph, Anne; Hewison, Jenny

    2014-02-18

    There is growing recognition of the value of conducting qualitative research with trials in health research. It is timely to reflect on how this qualitative research is presented in grant proposals to identify lessons for researchers and research commissioners. As part of a larger study focusing on how to maximise the value of undertaking qualitative research with trials, we undertook a documentary analysis of proposals of funded studies. Using the metaRegister of Controlled Trials (mRCT) database we identified trials funded in the United Kingdom, ongoing between 2001 and 2010, and reporting the use of qualitative research. We requested copies of proposals from lead researchers. We extracted data from the proposals using closed and open questions, analysed using descriptive statistics and content analysis respectively. 2% (89/3812) of trials in the mRCT database described the use of qualitative research undertaken with the trial. From these 89 trials, we received copies of 36 full proposals, of which 32 met our inclusion criteria. 25% used less than a single paragraph to describe the qualitative research. The aims of the qualitative research described in these proposals focused mainly on the intervention or trial conduct. Just over half (56%) of the proposals included an explicit rationale for conducting the qualitative research with the trial, the most frequent being to optimise implementation into clinical practice or to interpret trial findings. Key information about methods, expertise and resources was missing in a large minority of proposals, in particular sample size, type of analysis, and non-personnel resources. 28% specifically stated that qualitative researchers would conduct the qualitative research. Our review of proposals of successfully funded studies identified good practice but also identified limited space given to describing the qualitative research, with an associated lack of attention to the rationale for doing the qualitative research and

  7. Cancer clinical trials in persons with HIV infection.

    Science.gov (United States)

    Little, Richard F

    2017-01-01

    The era of modern HIV therapeutics is well underway. The cancer and infectious disease epidemiology of HIV disease has markedly altered as populations are availed to the benefits of antiretroviral therapy (ARV). The types of cancers occurring among those with HIV infection has broadened but the case burden in absolute numbers is very low relative to the background population. There are fewer incident cases of the AIDS-defining cancers (aggressive B-cell lymphomas, Kaposi's sarcoma, and cervical cancer). There is an increased risk for certain non-AIDS-defining cancers, but these occur somewhat sporadically relative to clinical trial enrollment. The changing epidemiology of cancer in HIV poses challenges as well as opportunities for participation of persons with HIV in cancer therapy clinical trials. There are excellent examples of cancer trials that inform cancer therapy for patients with HIV infection. Examples include those from HIV-specific trials and from trials mainly focused on the background population that included patients with HIV infection. Interpretation of clinical trials to guide therapy for those with HIV infection and cancer largely depends on data that does not include HIV-infected patients. The ability to extend clinical trial findings to populations not included in clinical trials remains problematic for a variety of populations, including those with HIV or AIDS. Careful prioritization of studies designed to bridge this gap is needed. However, there are published studies that serve as excellent examples bridging these gaps and the portfolio of cancer therapy trials underway will inform HIV and cancer better than at any time in the past.

  8. Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough).

    Science.gov (United States)

    Glickman, L T; Appel, M J

    1981-08-01

    Two field trials were conducted during periods of endemic (summer) and epizootic (winter) canine infectious tracheobronchitis activity to evaluate the efficacy of three intranasal vaccines in a closed commercial beagle breeding kennel. A trivalent vaccine containing Bordetella bronchiseptica, canine parainfluenza, and canine adenovirus-2 was administered at 3 weeks of age. The vaccine was 71.2% and 81.8% effective in decreasing the incidence of coughing during the winter and summer trials, respectively. The number of deaths was lower in each of the vaccine groups than in the placebo groups. No adverse reactions were observed with any of the intranasal vaccines.

  9. Closed and open breathing circuit function in healthy volunteers during exercise at Mount Everest base camp (5300 m)

    NARCIS (Netherlands)

    McMorrow, R. C. N.; Windsor, J. S.; Hart, N. D.; Richards, P.; Rodway, G. W.; Ahuja, V. Y.; O'Dwyer, M. J.; Mythen, M. G.; Grocott, M. P. W.; Ahuja, V.; Aref-Adib, G.; Burnham, R.; Chisholm, A.; Clarke, K.; Coates, D.; Coates, M.; Cook, D.; Cox, M.; Dhillon, S.; Dougall, C.; Doyle, P.; Duncan, P.; Edsell, M.; Edwards, L.; Evans, L.; Gardiner, P.; Grocott, M.; Gunning, P.; Hart, N.; Harrington, J.; Harvey, J.; Holloway, C.; Howard, D.; Hurlbut, D.; Imray, C.; Ince, C.; Jonas, M.; van der Kaaij, J.; Khosravi, M.; Kolfschoten, N.; Levett, D.; Luery, H.; Luks, A.; Martin, D.; McMorrow, R.; Meale, P.; Mitchell, K.; Montgomery, H.; Morgan, G.; Morgan, J.

    2012-01-01

    We present a randomised, controlled, crossover trial of the Caudwell Xtreme Everest (CXE) closed circuit breathing system vs an open circuit and ambient air control in six healthy, hypoxic volunteers at rest and exercise at Everest Base Camp, at 5300 m. Compared with control, arterial oxygen

  10. UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum: protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Craig Fiona F

    2012-04-01

    Full Text Available Abstract Background Pyoderma gangrenosum (PG is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day to prednisolone (0.75 mg/kg/day. A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers. Secondary outcomes include: (i time to healing; (ii global assessment of improvement; (iii PG inflammation assessment scale score; (iv self-reported pain; (v health-related quality of life; (vi time to recurrence; (vii treatment failures; (viii adverse reactions to study medications; and (ix cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG; measurable ulceration (that is, not pustular PG; and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size

  11. [Clinical trial data management and quality metrics system].

    Science.gov (United States)

    Chen, Zhao-hua; Huang, Qin; Deng, Ya-zhong; Zhang, Yue; Xu, Yu; Yu, Hao; Liu, Zong-fan

    2015-11-01

    Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry.

  12. Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes.

    Science.gov (United States)

    Feldman, Eva L; Boulis, Nicholas M; Hur, Junguk; Johe, Karl; Rutkove, Seward B; Federici, Thais; Polak, Meraida; Bordeau, Jane; Sakowski, Stacey A; Glass, Jonathan D

    2014-03-01

    The US Food and Drug Administration-approved trial, "A Phase 1, Open-Label, First-in-Human, Feasibility and Safety Study of Human Spinal Cord-Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis, Protocol Number: NS2008-1," is complete. Our overall objective was to assess the safety and feasibility of stem cell transplantation into lumbar and/or cervical spinal cord regions in amyotrophic lateral sclerosis (ALS) subjects. Preliminary results have been reported on the initial trial cohort of 12 ALS subjects. Here, we describe the safety and functional outcome monitoring results for the final trial cohort, consisting of 6 ALS subjects receiving 5 unilateral cervical intraspinal neural stem cell injections. Three of these subjects previously received 10 total bilateral lumbar injections as part of the earlier trial cohort. All injections utilized a novel spinal-mounted stabilization and injection device to deliver 100,000 neural stem cells per injection, for a dosing range up to 1.5 million cells. Subject assessments included detailed pre- and postsurgical neurological outcome measures. The cervical injection procedure was well tolerated and disease progression did not accelerate in any subject, verifying the safety and feasibility of cervical and dual-targeting approaches. Analyses on outcome data revealed preliminary insight into potential windows of stem cell biological activity and identified clinical assessment measures that closely correlate with ALS Functional Rating Scale-Revised scores, a standard assessment for ALS clinical trials. This is the first report of cervical and dual-targeted intraspinal transplantation of neural stem cells in ALS subjects. This approach is feasible and well-tolerated, supporting future trial phases examining therapeutic dosing and efficacy. © 2014 Child Neurology Society/American Neurological Association.

  13. A randomised controlled multicentre trial of treatments for adolescent anorexia nervosa including assessment of cost-effectiveness and patient acceptability - the TOuCAN trial.

    Science.gov (United States)

    Gowers, S G; Clark, A F; Roberts, C; Byford, S; Barrett, B; Griffiths, A; Edwards, V; Bryan, C; Smethurst, N; Rowlands, L; Roots, P

    2010-03-01

    To evaluate the clinical effectiveness and cost-effectiveness of inpatient compared with outpatient treatment and general (routine) treatment in Child and Adolescent Mental Health Services (CAMHS) against specialist treatment for young people with anorexia nervosa. In addition, to determine young people's and their carers' satisfaction with these treatments. A population-based, pragmatic randomised controlled trial (RCT) was carried out on young people age 12 to 18 presenting to community CAMHS with anorexia nervosa. Thirty-five English CAMHS in the north-west of England co-ordinated through specialist centres in Manchester and Liverpool. Two hundred and fifteen young people (199 female) were identified, of whom 167 (mean age 14 years 11 months) were randomised and 48 were followed up as a preference group. Randomised patients were allocated to either inpatient treatment in one of four units with considerable experience in the treatment of anorexia nervosa, a specialist outpatient programme delivered in one of two centres, or treatment as usual in general community CAMHS. The outpatient programmes spanned 6 months of treatment. The length of inpatient treatment was determined on a case-by-case basis on clinical need with outpatient follow-up to a minimum of 6 months. Follow-up assessments were carried out at 1, 2 and 5 years. The primary outcome measure was the Morgan-Russell Average Outcome Scale (MRAOS) and associated categorical outcomes. Secondary outcome measures included physical measures of weight, height, body mass index (BMI) and % weight for height. Research ratings included the Health of the National Outcome Scale for Children and Adolescents (HoNOSCA). Self report measures comprised the user version of HoNOSCA (HoNOSCA-SR), the Eating Disorder Inventory 2 (EDI-2), the Family Assessment Device (FAD) and the recent Mood and Feelings Questionnaire (MFQ). Information on resource use was collected in interview at 1, 2 and 5 years using the Child and

  14. Intralesional immunotherapy with tuberculin purified protein derivative (PPD) in recalcitrant wart: A randomized, placebo-controlled, double-blind clinical trial including an extra group of candidates for cryotherapy.

    Science.gov (United States)

    Amirnia, Mehdi; Khodaeiani, Effat; Fouladi, Daniel F; Masoudnia, Sima

    2016-01-01

    Due to paucity of randomized clinical trials, intralesional immunotherapy has not been yet accepted as a standard therapeutic method. To examine the efficacy and safety of intralesional immunotherapy with tuberculin purified protein derivative (PPD) for treating recalcitrant wart. In this randomized, placebo-controlled, double-blind clinical trial, a total of 69 patients with recalcitrant warts received either intralesional PPD antigen (n = 35) or intralesional saline (n = 34) for six times at 2-week intervals. A third group of candidates for cryotherapy (n = 33) was also included. The decrease in lesion size (good: complete response, intermediate: 50-99% improvement, poor: PPD patients; 0%, 14.7% and 85.3% of the placebo patients and 18.2%, 33.3% and 48.5% of the cryotherapy patients, respectively (PPD versus placebo: p PPD versus cryotherapy: p PPD group. The recurrence rate was 8.6%, 5.9% and 24.2% in the PPD, placebo and cryotherapy groups, respectively (p > 0.05). Intralesional immunotherapy with PPD antigen is highly effective and safe for treating recalcitrant warts. IRCT201407089844N3 in the Iranian Registry of Clinical Trials (IRCT).

  15. Inflation in a closed universe

    Science.gov (United States)

    Ratra, Bharat

    2017-11-01

    To derive a power spectrum for energy density inhomogeneities in a closed universe, we study a spatially-closed inflation-modified hot big bang model whose evolutionary history is divided into three epochs: an early slowly-rolling scalar field inflation epoch and the usual radiation and nonrelativistic matter epochs. (For our purposes it is not necessary to consider a final dark energy dominated epoch.) We derive general solutions of the relativistic linear perturbation equations in each epoch. The constants of integration in the inflation epoch solutions are determined from de Sitter invariant quantum-mechanical initial conditions in the Lorentzian section of the inflating closed de Sitter space derived from Hawking's prescription that the quantum state of the universe only include field configurations that are regular on the Euclidean (de Sitter) sphere section. The constants of integration in the radiation and matter epoch solutions are determined from joining conditions derived by requiring that the linear perturbation equations remain nonsingular at the transitions between epochs. The matter epoch power spectrum of gauge-invariant energy density inhomogeneities is not a power law, and depends on spatial wave number in the way expected for a generalization to the closed model of the standard flat-space scale-invariant power spectrum. The power spectrum we derive appears to differ from a number of other closed inflation model power spectra derived assuming different (presumably non de Sitter invariant) initial conditions.

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

    Science.gov (United States)

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

    2018-01-08

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

  17. Closed cooling water chemistry guidelines revision

    International Nuclear Information System (INIS)

    McElrath, Joel; Breckenridge, Richard

    2014-01-01

    This second revision of the Closed Cooling Water Chemistry Guideline addresses the use of chemicals and monitoring methods to mitigate corrosion, fouling, and microbiological growth in the closed cooling-water (CCW) systems of nuclear and fossil-fueled power plants. This revision has been endorsed by the utility chemistry community and represents another step in developing a more proactive chemistry program to limit or control closed cooling system degradation with increased consideration of corporate resources and plant-specific design and operating concerns. These guidelines were developed using laboratory data, operating experience, and input from organizations and utilities within and outside of the United States of America. It is the intent of the Revision Committee that these guidelines are applicable to all nuclear and fossil-fueled generating stations around the world. A committee of industry experts—including utility specialists, Institute of Nuclear Power Operations representatives, water-treatment service-company representatives, consultants, a primary contractor, and EPRI staff—collaborated in reviewing available data on closed cooling-water system corrosion and microbiological issues. Recognizing that each plant owner has a unique set of design, operating, and corporate concerns, the Guidelines Committee developed a methodology for plant-specific optimization. The guideline provides the technical basis for a reasonable but conservative set of chemical treatment and monitoring programs. The use of operating ranges for the various treatment chemicals discussed in this guideline will allow a power plant to limit corrosion, fouling, and microbiological growth in CCW systems to acceptable levels. The guideline now includes closed cooling chemistry regimes proven successful in use in the international community. The guideline provides chemistry constraints for the use of phosphates control, as well as pure water with pH control. (author)

  18. Esthetic judgments of palatally displaced canines 3 months postdebond after surgical exposure with either a closed or an open technique.

    Science.gov (United States)

    Parkin, Nicola A; Freeman, Jennifer V; Deery, Chris; Benson, Philip E

    2015-02-01

    The aim of this study was to compare the esthetic judgments of orthodontists and laypeople regarding the appearance of palatally displaced canines 3 months after treatment with either a closed or an open surgical exposure and orthodontic alignment. A multicenter randomized controlled trial was undertaken in 3 hospitals in the United Kingdom. Patients with unilateral palatally displaced canines were randomly allocated to receive either a closed or an open surgical exposure. The teeth were aligned with fixed appliances, and 3 months after debond, intraoral photographs were taken. The photographs were projected in random order to 2 panels of judges (orthodontists and laypeople), who completed a questionnaire. The images of 67 participants (closed, 33; open, 34) were included. The laypeople were able to identify the operated tooth only 49.7% of the time (95% CI, 45.3%-54.0%); this was no better than chance (P = 0.880). The orthodontists were more successful but still identified the treated canine with certainty only 60.7% of the time (95% CI, 53.7%-67.8%; P = 0.003). Both panels more frequently assessed the unoperated canine to have a better appearance than the contralateral operated canine; however, there were no differences between the closed and open groups (proportion preferring unoperated canine-laypeople: closed, 58.7%; open, 57.0%; P = 0.43; and orthodontists: closed, 60.9%; open, 60.6%; P = 0.27). There is an esthetic impact to aligning a palatally displaced canine, but it is mostly minor and unlikely to be detectable by laypeople. The esthetic impact was the same, whether the canine was exposed with a closed or an open surgical technique. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  19. Impact of Scribes on Physician Satisfaction, Patient Satisfaction, and Charting Efficiency: A Randomized Controlled Trial.

    Science.gov (United States)

    Gidwani, Risha; Nguyen, Cathina; Kofoed, Alexis; Carragee, Catherine; Rydel, Tracy; Nelligan, Ian; Sattler, Amelia; Mahoney, Megan; Lin, Steven

    2017-09-01

    Scribes are increasingly being used in clinical practice despite a lack of high-quality evidence regarding their effects. Our objective was to evaluate the effect of medical scribes on physician satisfaction, patient satisfaction, and charting efficiency. We conducted a randomized controlled trial in which physicians in an academic family medicine clinic were randomized to 1 week with a scribe then 1 week without a scribe for the course of 1 year. Scribes drafted all relevant documentation, which was reviewed by the physician before attestation and signing. In encounters without a scribe, the physician performed all charting duties. Our outcomes were physician satisfaction, measured by a 5-item instrument that included physicians' perceptions of chart quality and chart accuracy; patient satisfaction, measured by a 6-item instrument; and charting efficiency, measured by time to chart close. Scribes improved all aspects of physician satisfaction, including overall satisfaction with clinic (OR = 10.75), having enough face time with patients (OR = 3.71), time spent charting (OR = 86.09), chart quality (OR = 7.25), and chart accuracy (OR = 4.61) (all P values patient satisfaction. Scribes increased the proportion of charts that were closed within 48 hours (OR =1.18, P =.028). To our knowledge, we have conducted the first randomized controlled trial of scribes. We found that scribes produced significant improvements in overall physician satisfaction, satisfaction with chart quality and accuracy, and charting efficiency without detracting from patient satisfaction. Scribes appear to be a promising strategy to improve health care efficiency and reduce physician burnout. © 2017 Annals of Family Medicine, Inc.

  20. Artificial Pancreas Device Systems for the Closed-Loop Control of Type 1 Diabetes: What Systems Are in Development?

    Science.gov (United States)

    Trevitt, Sara; Simpson, Sue; Wood, Annette

    2016-05-01

    Closed-loop artificial pancreas device (APD) systems are externally worn medical devices that are being developed to enable people with type 1 diabetes to regulate their blood glucose levels in a more automated way. The innovative concept of this emerging technology is that hands-free, continuous, glycemic control can be achieved by using digital communication technology and advanced computer algorithms. A horizon scanning review of this field was conducted using online sources of intelligence to identify systems in development. The systems were classified into subtypes according to their level of automation, the hormonal and glycemic control approaches used, and their research setting. Eighteen closed-loop APD systems were identified. All were being tested in clinical trials prior to potential commercialization. Six were being studied in the home setting, 5 in outpatient settings, and 7 in inpatient settings. It is estimated that 2 systems may become commercially available in the EU by the end of 2016, 1 during 2017, and 2 more in 2018. There are around 18 closed-loop APD systems progressing through early stages of clinical development. Only a few of these are currently in phase 3 trials and in settings that replicate real life. © 2015 Diabetes Technology Society.

  1. Compliance with the CONSORT checklist in obstetric anaesthesia randomised controlled trials.

    Science.gov (United States)

    Halpern, S H; Darani, R; Douglas, M J; Wight, W; Yee, J

    2004-10-01

    The Consolidated Standards for Reporting of Trials (CONSORT) checklist is an evidence-based approach to help improve the quality of reporting randomised controlled trials. The purpose of this study was to determine how closely randomised controlled trials in obstetric anaesthesia adhere to the CONSORT checklist. We retrieved all randomised controlled trials pertaining to the practice of obstetric anaesthesia and summarised in Obstetric Anesthesia Digest between March 2001 and December 2002 and compared the quality of reporting to the CONSORT checklist. The median number of correctly described CONSORT items was 65% (range 36% to 100%). Information pertaining to randomisation, blinding of the assessors, sample size calculation, reliability of measurements and reporting of the analysis were often omitted. It is difficult to determine the value and quality of many obstetric anaesthesia clinical trials because journal editors do not insist that this important information is made available to readers. Both clinicians and clinical researchers would benefit from uniform reporting of randomised trials in a manner that allows rapid data retrieval and easy assessment for relevance and quality.

  2. Use of 'sham' radiotherapy in randomized clinical trials

    International Nuclear Information System (INIS)

    Schwarz, F.; Christie, D.

    2008-01-01

    The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970-2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macular degeneration and Graves' ophthalmopathy. There were no trials relating to the use of radiotherapy in the treatment of malignancy. This review showed that it is possible to carry out sham radiotherapy with due regard for ethical concerns, with effective blinding and high levels of patient acceptance. Large sample sizes with multicentre trial designs were achievable. Although the statistical philosophy for using sham radiotherapy in trials is legitimate, it is no longer routinely used.

  3. A Public Trial De Novo

    DEFF Research Database (Denmark)

    Vedel, Jane Bjørn; Gad, Christopher

    2011-01-01

    This article addresses the concept of “industrial interests” and examines its role in a topical controversy about a large research grant from a private foundation, the Novo Nordisk Foundation, to the University of Copenhagen. The authors suggest that the debate took the form of a “public trial” w.......” The article ends with a discussion of some implications of the analysis, including that policy making, academic research, and public debates might benefit from more detailed accounts of interests and stakes.......This article addresses the concept of “industrial interests” and examines its role in a topical controversy about a large research grant from a private foundation, the Novo Nordisk Foundation, to the University of Copenhagen. The authors suggest that the debate took the form of a “public trial......” where the grant and close(r) intermingling between industry and public research was prosecuted and defended. First, the authors address how the grant was framed in the media. Second, they redescribe the case by introducing new “evidence” that, because of this framing, did not reach “the court...

  4. A mechanism for the dynamo terms to sustain closed-flux current, including helicity balance, by driving current which crosses the magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Jarboe, T. R.; Nelson, B. A.; Sutherland, D. A. [University of Washington, Seattle, Washington 98195 (United States)

    2015-07-15

    An analysis of imposed dynamo current drive (IDCD) [T.R. Jarboe et al., Nucl. Fusion 52 083017 (2012)] reveals: (a) current drive on closed flux surfaces seems possible without relaxation, reconnection, or other flux-surface-breaking large events; (b) the scale size of the key physics may be smaller than is often computationally resolved; (c) helicity can be sustained across closed flux; and (d) IDCD current drive is parallel to the current which crosses the magnetic field to produce the current driving force. In addition to agreeing with spheromak data, IDCD agrees with selected tokamak data.

  5. Clinical Trials

    Medline Plus

    Full Text Available ... and organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and ...

  6. Power, fairness and trust: understanding and engaging with vaccine trial participants and communities in the setting up the EBOVAC-Salone vaccine trial in Sierra Leone

    Directory of Open Access Journals (Sweden)

    Luisa Enria

    2016-11-01

    Full Text Available Abstract Background This paper discusses the establishment of a clinical trial of an Ebola vaccine candidate in Kambia District, Northern Sierra Leone during the epidemic, and analyses the role of social science research in ensuring that lessons from the socio-political context, the recent experience of the Ebola outbreak, and learning from previous clinical trials were incorporated in the development of community engagement strategies. The paper aims to provide a case study of an integrated social science and communications system in the start-up phase of the clinical trial. Methods The paper is based on qualitative research methods including ethnographic observation, interviews with trial participants and key stakeholder interviews. Results Through the case study of EBOVAC Salone, the paper suggests ways in which research can be used to inform communication strategies before and during the setting up of the trial. It explores notions of power, fairness and trust emerging from analysis of the Sierra Leonean context and through ethnographic research, to reflect on three situations in which social scientists and community liaison officers worked together to ensure successful community engagement. Firstly, a section on “power” considers the pitfalls of considering communities as homogeneous and shows the importance of understanding intra-community power dynamics when engaging communities. Secondly, a section on “fairness” shows how local understandings of what is fair can help inform the design of volunteer recruitment strategies. Finally, a section on “trust” highlights how historically rooted rumours can be effectively addressed through active dialogue rather than through an approach focused on correcting misinformation. Conclusion The paper firstly emphasises the value of social science in the setting up of clinical trials, in terms of providing an in depth understanding of context and social dynamics. Secondly, the paper suggests

  7. VRPI Temporal Progression of Closed Globe Injury from Blast Exposure

    Science.gov (United States)

    2015-09-01

    significant increases in VEGF have been reported in many ocular disorders including diabetic retinopathy , diffuse macular edema, retinal vein...Open globe injury is often readily identifiable and typically undergoes urgent surgical repair. However, closed globe injury may not be detected ...including shrapnel or debris to the eye, is easily identified and rapidly treated. Closed globe trauma may not be detected right away, and little is

  8. Involvement of consumers in studies run by the Medical Research Council Clinical Trials Unit: Results of a survey

    Directory of Open Access Journals (Sweden)

    Vale Claire L

    2012-01-01

    Full Text Available Abstract Background We aimed to establish levels of consumer involvement in randomised controlled trials (RCTs, meta-analyses and other studies carried out by the UK Medical Research Council (MRC Clinical Trials Unit across the range of research programs, predominantly in cancer and HIV. Methods Staff responsible for studies that were included in a Unit Progress Report (MRC CTU, April 2009 were asked to complete a semi-structured questionnaire survey regarding consumer involvement. This was defined as active involvement of consumers as partners in the research process and not as subjects of that research. The electronic questionnaires combined open and closed questions, intended to capture quantitative and qualitative information on whether studies had involved consumers; types of activities undertaken; recruitment and support; advantages and disadvantages of involvement and its perceived impact on aspects of the research. Results Between October 2009 and April 2010, 138 completed questionnaires (86% were returned. Studies had been conducted over a 20 year period from 1989, and around half were in cancer; 30% in HIV and 20% were in other disease areas including arthritis, tuberculosis and blood transfusion medicine. Forty-three studies (31% had some consumer involvement, most commonly as members of trial management groups (TMG [88%]. A number of positive impacts on both the research and the researcher were identified. Researchers generally felt involvement was worthwhile and some felt that consumer involvement had improved the credibility of the research. Benefits in design and quality, trial recruitment, dissemination and decision making were also perceived. Researchers felt they learned from consumer involvement, albeit that there were some barriers. Conclusions Whilst most researchers identified benefits of involving consumers, most of studies included in the survey had no involvement. Information from this survey will inform the development

  9. Involvement of consumers in studies run by the Medical Research Council Clinical Trials Unit: results of a survey.

    Science.gov (United States)

    Vale, Claire L; Thompson, Lindsay C; Murphy, Claire; Forcat, Silvia; Hanley, Bec

    2012-01-13

    We aimed to establish levels of consumer involvement in randomised controlled trials (RCTs), meta-analyses and other studies carried out by the UK Medical Research Council (MRC) Clinical Trials Unit across the range of research programs, predominantly in cancer and HIV. Staff responsible for studies that were included in a Unit Progress Report (MRC CTU, April 2009) were asked to complete a semi-structured questionnaire survey regarding consumer involvement. This was defined as active involvement of consumers as partners in the research process and not as subjects of that research. The electronic questionnaires combined open and closed questions, intended to capture quantitative and qualitative information on whether studies had involved consumers; types of activities undertaken; recruitment and support; advantages and disadvantages of involvement and its perceived impact on aspects of the research. Between October 2009 and April 2010, 138 completed questionnaires (86%) were returned. Studies had been conducted over a 20 year period from 1989, and around half were in cancer; 30% in HIV and 20% were in other disease areas including arthritis, tuberculosis and blood transfusion medicine. Forty-three studies (31%) had some consumer involvement, most commonly as members of trial management groups (TMG) [88%]. A number of positive impacts on both the research and the researcher were identified. Researchers generally felt involvement was worthwhile and some felt that consumer involvement had improved the credibility of the research. Benefits in design and quality, trial recruitment, dissemination and decision making were also perceived. Researchers felt they learned from consumer involvement, albeit that there were some barriers. Whilst most researchers identified benefits of involving consumers, most of studies included in the survey had no involvement. Information from this survey will inform the development of a unit policy on consumer involvement, to guide future

  10. Clinical Trials

    Medline Plus

    Full Text Available ... study explored whether the benefits of lowering high blood pressure in the elderly outweighed the risks. Other examples of clinical trials that test principles or strategies include studies that explore whether ...

  11. Generalized modal analysis for closed-loop piezoelectric devices

    International Nuclear Information System (INIS)

    Giraud-Audine, Christophe; Giraud, Frédéric; Amberg, Michel; Lemaire-Semail, Betty

    2015-01-01

    Stress in a piezoelectric material can be controlled by imposing an electrical field. Thanks to feedback, this electrical field can be a function of some strain-related measurement so as to confer on the piezoelectric device a closed-loop macroscopic behaviour. In this paper we address the modelling of such a system by extending the modal decomposition methods to account for the closed loop. To do so, the boundary conditions are modified to include the electrical feedback circuit, hence allowing a closed-loop modal analysis. A case study is used to illustrate the theory and to validate it. The main advantage of the method is that design issues such as the coupling factor of the device and closed-loop stability are simultaneously captured. (paper)

  12. Effect of reporting bias on meta-analyses of drug trials

    DEFF Research Database (Denmark)

    Hart, Beth; Lundh, Andreas; Bero, Lisa

    2012-01-01

    To investigate the effect of including unpublished trial outcome data obtained from the Food and Drug Administration (FDA) on the results of meta-analyses of drug trials.......To investigate the effect of including unpublished trial outcome data obtained from the Food and Drug Administration (FDA) on the results of meta-analyses of drug trials....

  13. Efficacy of Manual Therapy Including Neurodynamic Techniques for the Treatment of Carpal Tunnel Syndrome: A Randomized Controlled Trial.

    Science.gov (United States)

    Wolny, Tomasz; Saulicz, Edward; Linek, Paweł; Shacklock, Michael; Myśliwiec, Andrzej

    2017-05-01

    The purpose of this randomized trial was to compare the efficacy of manual therapy, including the use of neurodynamic techniques, with electrophysical modalities on patients with mild and moderate carpal tunnel syndrome (CTS). The study included 140 CTS patients who were randomly assigned to the manual therapy (MT) group, which included the use of neurodynamic techniques, functional massage, and carpal bone mobilizations techniques, or to the electrophysical modalities (EM) group, which included laser and ultrasound therapy. Nerve conduction, pain severity, symptom severity, and functional status measured by the Boston Carpal Tunnel Questionnaire were assessed before and after treatment. Therapy was conducted twice weekly and both groups received 20 therapy sessions. A baseline assessment revealed group differences in sensory conduction of the median nerve (P < .01) but not in motor conduction (P = .82). Four weeks after the last treatment procedure, nerve conduction was examined again. In the MT group, median nerve sensory conduction velocity increased by 34% and motor conduction velocity by 6% (in both cases, P < .01). There was no change in median nerve sensory and motor conduction velocities in the EM. Distal motor latency was decreased (P < .01) in both groups. A baseline assessment revealed no group differences in pain severity, symptom severity, or functional status. Immediately after therapy, analysis of variance revealed group differences in pain severity (P < .01), with a reduction in pain in both groups (MT: 290%, P < .01; EM: 47%, P < .01). There were group differences in symptom severity (P < .01) and function (P < .01) on the Boston Carpal Tunnel Questionnaire. Both groups had an improvement in functional status (MT: 47%, P < .01; EM: 9%, P < .01) and a reduction in subjective CTS symptoms (MT: 67%, P < .01; EM: 15%, P < .01). Both therapies had a positive effect on nerve conduction, pain reduction, functional status, and subjective symptoms in

  14. Estimation of hull girder vertical bending moments including non-linear and flexibility effects using closed form expressions

    DEFF Research Database (Denmark)

    Pedersen, Preben Terndrup; Jensen, Jørgen Juncher

    2009-01-01

    A simple but rational procedure for prediction of extreme wave-induced hull girder bending moment is presented. The procedure takes into account main ship hull characteristics such as: length, breadth, draught, block coefficient, bow flare coefficient, forward speed and hull flexibility. The wave......-linear strip theory calculations and supplemented with new closed form results for the hogging bending moment. Focus is on the extreme hull girder hogging bending moment. Due to the few input parameters this procedure can be used to estimate the wave-induced bending moments at the conceptual design phase....... Another application area is for novel single hull ship types not presently covered by the rules of the classification societies. As one application example the container ship M/S Napoli is considered....

  15. Credentialing for participation in clinical trials

    International Nuclear Information System (INIS)

    Followill, David S.; Urie, Marcia; Galvin, James M.; Ulin, Kenneth; Xiao, Ying; FitzGerald, Thomas J.

    2012-01-01

    The National Cancer Institute (NCI) clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials.

  16. Credentialing for participation in clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Followill, David S. [Radiological Physics Center, Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Urie, Marcia [Quality Assurance Review Center, Department of Radiation Oncology, University of Massachusetts Medical School, Lincoln, RI (United States); Galvin, James M. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Radiation Therapy Oncology Group, Philadelphia, PA (United States); Ulin, Kenneth [Quality Assurance Review Center, Department of Radiation Oncology, University of Massachusetts Medical School, Lincoln, RI (United States); Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA (United States); Xiao, Ying [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Radiation Therapy Oncology Group, Philadelphia, PA (United States); FitzGerald, Thomas J., E-mail: dfollowi@mdanderson.org [Quality Assurance Review Center, Department of Radiation Oncology, University of Massachusetts Medical School, Lincoln, RI (United States); Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, MA (United States)

    2012-12-26

    The National Cancer Institute (NCI) clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence-based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials.

  17. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters.

    Science.gov (United States)

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-12-01

    The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled "Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers" (Haass-Koffler et al., 2017) [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK) parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73.

  18. Interim data monitoring to enroll higher-risk participants in HIV prevention trials

    Directory of Open Access Journals (Sweden)

    Umo-Otong John

    2009-06-01

    Full Text Available Abstract Background Lower-than-expected incidence of HIV undermines sample size calculations and compromises the power of a HIV prevention trial. We evaluated the effectiveness of interim monitoring of HIV infection rates and on-going modification of recruitment strategies to enroll women at higher risk of HIV in the Cellulose Sulfate Phase III study in Nigeria. Methods We analyzed prevalence and incidence of HIV and other sexually transmitted infections, demographic and sexual behavior characteristics aggregated over the treatment groups on a quarterly basis. The site investigators were advised on their recruitment strategies based on the findings of the interim analyses. Results A total of 3619 women were screened and 1644 enrolled at the Ikeja and Apapa clinics in Lagos, and at the Central and Peripheral clinics in Port Harcourt. Twelve months after study initiation, the overall incidence of HIV was less than one-third of the pre-study assumption, with rates of HIV that varied substantially between clinics. Due to the low prevalence and incidence rates of HIV, it was decided to close the Ikeja clinic in Lagos and to find new catchment areas in Port Harcourt. This strategy was associated with an almost two-fold increase in observed HIV incidence during the second year of the study. Conclusion Given the difficulties in estimating HIV incidence, a close monitoring of HIV prevalence and incidence rates during a trial is warranted. The on-going modification of recruitment strategies based on the regular analysis of HIV rates appeared to be an efficient method for targeting populations at greatest risk of HIV infection and increasing study power in the Nigeria trial. Trial Registration The trial was registered with the ClinicalTrials.gov registry under #NCT00120770 http://clinicaltrials.gov/ct2/show/NCT00120770

  19. Summary report on close-coupled subsurface barrier technology: Initial field trials to full-scale demonstration

    International Nuclear Information System (INIS)

    Heiser, J.H.

    1997-09-01

    The primary objective of this project was to develop and demonstrate the installation and measure the performance of a close-coupled barrier for the containment of subsurface waste or contaminant migration. A close-coupled barrier is produced by first installing a conventional, low-cost, cement-grout containment barrier followed by a thin lining of a polymer grout. The resultant barrier is a cement-polymer composite that has economic benefits derived from the cement and performance benefits from the durable and resistant polymer layer. The technology has matured from a regulatory investigation of the issues concerning the use of polymers to laboratory compatibility and performance measurements of various polymer systems to a pilot-scale, single column injection at Sandia to full-scale demonstration. The feasibility of the close-coupled barrier concept was proven in a full-scale cold demonstration at Hanford, Washington and then moved to the final stage with a full-scale demonstration at an actual remediation site at Brookhaven National Laboratory (BNL). At the Hanford demonstration the composite barrier was emplaced around and beneath a 20,000 liter tank. The secondary cement layer was constructed using conventional jet grouting techniques. Drilling was completed at a 45 degree angle to the ground, forming a cone-shaped barrier. The primary barrier was placed by panel jet-grouting with a dual-wall drill stem using a two part polymer grout. The polymer chosen was a high molecular weight acrylic. At the BNL demonstration a V-trough barrier was installed using a conventional cement grout for the secondary layer and an acrylic-gel polymer for the primary layer. Construction techniques were identical to the Hanford installation. This report summarizes the technology development from pilot- to full-scale demonstrations and presents some of the performance and quality achievements attained

  20. Effects of standard training in the use of closed-circuit televisions in visually impaired adults: design of a training protocol and a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    van Rens Ger HMB

    2010-03-01

    Full Text Available Abstract Background Reading problems are frequently reported by visually impaired persons. A closed-circuit television (CCTV can be helpful to maintain reading ability, however, it is difficult to learn how to use this device. In the Netherlands, an evidence-based rehabilitation program in the use of CCTVs was lacking. Therefore, a standard training protocol needed to be developed and tested in a randomized controlled trial (RCT to provide an evidence-based training program in the use of this device. Methods/Design To develop a standard training program, information was collected by studying literature, observing training in the use of CCTVs, discussing the content of the training program with professionals and organizing focus and discussion groups. The effectiveness of the program was evaluated in an RCT, to obtain an evidence-based training program. Dutch patients (n = 122 were randomized into a treatment group: normal instructions from the supplier combined with training in the use of CCTVs, or into a control group: instructions from the supplier only. The effect of the training program was evaluated in terms of: change in reading ability (reading speed and reading comprehension, patients' skills to operate the CCTV, perceived (vision-related quality of life and tasks performed in daily living. Discussion The development of the CCTV training protocol and the design of the RCT in the present study may serve as an example to obtain an evidence-based training program. The training program was adjusted to the needs and learning abilities of individual patients, however, for scientific reasons it might have been preferable to standardize the protocol further, in order to gain more comparable results. Trial registration http://www.trialregister.nl, identifier: NTR1031

  1. VISTA-Rehab: a resource for stroke rehabilitation trials.

    Science.gov (United States)

    Ali, Myzoon; Ashburn, Ann; Bowen, Audrey; Brodie, Eric; Corr, Susan; Drummond, Avril; Edmans, Judi; Gladman, John; Kalra, Lalit; Langhorne, Peter; Lees, Kennedy R; Lincoln, Nadina; Logan, Pip; Mead, Gillian; Patchick, Emma; Pollock, Alex; Pomeroy, Val; Sackley, Catherine; Sunnerhagen, Katherina S; van Vliet, Paulette; Walker, Marion; Brady, Marian

    2010-12-01

    Stroke rehabilitation is a complex intervention. Many factors influence the interaction between the patient and the elements of the intervention. Rehabilitation interventions are aimed at altering different domains of patient outcome including body functions, activity and participation. As a consequence, randomised clinical trials in this area are difficult to design. We developed an archive of stroke rehabilitation trials (VISTA-Rehab) to act as a resource to help trialists model and design future rehabilitation studies. We developed specific eligibility criteria for the entry of stroke rehabilitation trials into the archive. We established a Steering Committee to oversee projects and publications and commenced the recruitment of rehabilitation trials into this resource. As of August 2009, VISTA-Rehab contains data from 23 stroke rehabilitation trials (>3400 patients). Demographic data, including age [median=73, interquartile range (63,79)], gender (male=53%) and initial dependency [median baseline Barthel index score=6, interquartile range (9,19)], are available for all patients. Outcome measures include the modified Rankin Scale, Barthel Index, Rivermead Motor Assessment, Fugl-Meyer Assessment, General Health Questionnaire and Nottingham Extended Activities of Daily Living Scale. VISTA-Rehab expands the Virtual International Stroke Trials Archive to include rehabilitation trials. Anonymised data can be used to examine questions specific to stroke rehabilitation and to generate novel hypotheses. © 2010 The Authors. International Journal of Stroke © 2010 World Stroke Organization.

  2. Clinical Trials

    Medline Plus

    Full Text Available ... include factors such as a patient's age and gender, the type and stage of disease, and whether ... How long will the trial last? Who will pay for the tests and treatments I receive? Will ...

  3. Clinical Trials

    Medline Plus

    Full Text Available ... a laboratory (lab), where scientists first develop and test new ideas. If an approach seems promising, the ... Centers (including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study ...

  4. Clinical Trials

    Medline Plus

    Full Text Available ... offer a variety of funding mechanisms tailored to planning and conducting clinical trials at all phases, including ... Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute of Health ...

  5. Clinical Trials

    Medline Plus

    Full Text Available ... Events About NHLBI About NHLBI Home Mission and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory ... offer a variety of funding mechanisms tailored to planning and conducting clinical trials at all phases, including ...

  6. Study on closed cycle MHD generation systems; Closed cycle MHD hatsuden system no kento

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1988-03-01

    The closed cycle noble gas MHD generation systems are surveyed and studied. The concept of closed cycle noble gas MHD generation is confirmed to extract high enthalpy, and now going into the engineering demonstration stage from the basic research stage. These systems have various characteristics. The highest working temperature is around 1,700 degrees C, which is close to that associated with the existing techniques. Use of helium or argon gas as the working fluid makes the system relatively free of various problems, e.g., corrosion. It can attain a much higher efficiency than the combined cycle involving gas turbine. It suffers less heat loss in the passages, is suitable for small- to medium-capacity power generation systems, and copes with varying load. The compact power generation passages decrease required size of the superconducting magnet. The technical problems to be solved include optimization of power generation conditions, demonstration of durability of the power generation passages, injection/recovery of the seed material, treatment of the working gas to remove molecular impurities, and development of heat exchangers serviceable at high temperature produced by direct combustion of coal. The conceptual designs of the triple combined system are completed. (NEDO)

  7. Patient engagement in clinical trials: The Clinical Trials Transformation Initiative's leadership from theory to practical implementation.

    Science.gov (United States)

    Patrick-Lake, Bray

    2018-02-01

    Patient engagement is an increasingly important aspect of successful clinical trials. Over the past decade, as patient group involvement in clinical trials has continued to increase and diversify, the Clinical Trials Transformation Initiative has not only recognized the crucial role patients play in improving the clinical trial enterprise but also made a deep commitment to help grow and shape the emerging field of patient engagement. This article describes the evolution of patient engagement including the origins of the patient engagement movement; barriers to successful engagement and remaining challenges to full and valuable collaboration between patient groups and trial sponsors; and Clinical Trials Transformation Initiative's role in influencing the field through organizational practices, formal project work and resulting recommendations, and external advocacy efforts.

  8. Closing the loop.

    Science.gov (United States)

    Dassau, E; Atlas, E; Phillip, M

    2010-02-01

    The dream of closing the loop is actually the dream of creating an artificial pancreas and freeing the patients from being involved with the care of their own diabetes. Insulin-dependent diabetes (type 1) is a chronic incurable disease which requires constant therapy without the possibility of any 'holidays' or insulin-free days. It means that patients have to inject insulin every day of their life, several times per day, and in order to do it safely they also have to measure their blood glucose levels several times per day. Patients need to plan their meals, their physical activities and their insulin regime - there is only very small room for spontaneous activities. This is why the desire for an artificial pancreas is so strong despite the fact that it will not cure the diabetic patients. Attempts to develop a closed-loop system started in the 1960s but never got to a clinical practical stage of development. In recent years the availability of continuous glucose sensors revived those efforts and stimulated the clinician and researchers to believe that closing the loop might be possible nowadays. Many papers have been published over the years describing several different ideas on how to close the loop. Most of the suggested systems have a sensing arm that measures the blood glucose repeatedly or continuously, an insulin delivery arm that injects insulin upon command and a computer that makes the decisions of when and how much insulin to deliver. The differences between the various published systems in the literature are mainly in their control algorithms. However, there are also differences related to the method and site of glucose measurement and insulin delivery. SC glucose measurements and insulin delivery are the most studied option but other combinations of insulin measurements and glucose delivery including intravascular and intraperitoneal (IP) are explored. We tried to select recent publications that we believe had influenced and inspired people interested

  9. Single-trial event-related potentials to significant stimuli.

    Science.gov (United States)

    Rushby, Jacqueline A; Barry, Robert J

    2009-11-01

    The stimulus-response pattern of the skin conductance response (SCR) was used as a model of the Orienting Reflex (OR) to assess the P1, N1, P2, N2 and late positive complex (LPC/P300) components of the ERP in a simple habituation paradigm, in which a single series of 12 innocuous tones were presented at a very long interstimulus interval (2 min). To maintain their waking state during this boring task, participants were instructed to alternately close or open their eyes to each stimulus. None of the baseline-to-peak ERP measures showed trials effects comparable with the marked habituation over trials shown by the SCRs. Principal Components Analysis was used to decompose the ERP, yielding factors identified as the N1, N2, P3a, P3b and Novelty P3 components. An additional factor represented later eye-movement activity. No trial effects were apparent for the N1, N2, P3a or P3b components. The Novelty P3 showed marked response decrement over trials. These results are discussed in relation to current conceptualisations of the OR.

  10. Clinical Trials

    Medline Plus

    Full Text Available ... organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and ... how you feel. Some people will need to travel or stay in hospitals to take part in ...

  11. Clinical Trials

    Medline Plus

    Full Text Available ... sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and Veterans Affairs; ... age and frequency for doing screening tests, such as mammography; and compare two or more screening tests ...

  12. Clinical Trials

    Medline Plus

    Full Text Available ... and organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense ... FOIA) Accessibility Copyright and Usage No FEAR Act Grants and Funding Building 31 31 Center Drive Bethesda, ...

  13. Recruitment strategies and challenges in a large intervention trial: Systolic Blood Pressure Intervention Trial.

    Science.gov (United States)

    Ramsey, Thomas M; Snyder, Joni K; Lovato, Laura C; Roumie, Christianne L; Glasser, Steven P; Cosgrove, Nora M; Olney, Christine M; Tang, Rocky H; Johnson, Karen C; Still, Carolyn H; Gren, Lisa H; Childs, Jeffery C; Crago, Osa L; Summerson, John H; Walsh, Sandy M; Perdue, Letitia H; Bankowski, Denise M; Goff, David C

    2016-06-01

    The Systolic Blood Pressure Intervention Trial is a multicenter, randomized clinical trial of 9361 participants with hypertension who are ≥50 years old. The trial is designed to evaluate the effect of intensive systolic blood pressure control (systolic blood pressure goal recruitment strategies and lessons learned during recruitment of the Systolic Blood Pressure Intervention Trial cohort and five targeted participant subgroups: pre-existing cardiovascular disease, pre-existing chronic kidney disease, age ≥75 years, women, and minorities. In collaboration with the National Institutes of Health Project Office and Systolic Blood Pressure Intervention Trial Coordinating Center, five Clinical Center Networks oversaw clinical site selection, recruitment, and trial activities. Recruitment began on 8 November 2010 and ended on 15 March 2013 (about 28 months). Various recruitment strategies were used, including mass mailing, brochures, referrals from healthcare providers or friends, posters, newspaper ads, radio ads, and electronic medical record searches. Recruitment was scheduled to last 24 months to enroll a target of 9250 participants; in just over 28 months, the trial enrolled 9361 participants. The trial screened 14,692 volunteers, with 33% of initial screens originating from the use of mass mailing lists. Screening results show that participants also responded to recruitment efforts through referral by Systolic Blood Pressure Intervention Trial staff, healthcare providers, or friends (45%); brochures or posters placed in clinic waiting areas (15%); and television, radio, newspaper, Internet ads, or toll-free numbers (8%). The overall recruitment yield (number randomized/number screened) was 64% (9361 randomized/14,692 screened), 77% for those with cardiovascular disease, 79% for those with chronic kidney disease, 70% for those aged ≥75 years, 55% for women, and 61% for minorities. As recruitment was observed to lag behind expectations, additional

  14. Te Ira Tangata: A Zelen randomised controlled trial of a treatment package including problem solving therapy compared to treatment as usual in Maori who present to hospital after self harm

    Directory of Open Access Journals (Sweden)

    Wikiriwhi Karen

    2011-05-01

    Full Text Available Abstract Background Maori, the indigenous people of New Zealand, who present to hospital after intentionally harming themselves, do so at a higher rate than non-Maori. There have been no previous treatment trials in Maori who self harm and previous reviews of interventions in other populations have been inconclusive as existing trials have been under powered and done on unrepresentative populations. These reviews have however indicated that problem solving therapy and sending regular postcards after the self harm attempt may be an effective treatment. There is also a small literature on sense of belonging in self harm and the importance of culture. This protocol describes a pragmatic trial of a package of measures which include problem solving therapy, postcards, patient support, cultural assessment, improved access to primary care and a risk management strategy in Maori who present to hospital after self harm using a novel design. Methods We propose to use a double consent Zelen design where participants are randomised prior to giving consent to enrol a representative cohort of patients. The main outcome will be the number of Maori scoring below nine on the Beck Hopelessness Scale. Secondary outcomes will be hospital repetition at one year; self reported self harm; anxiety; depression; quality of life; social function; and hospital use at three months and one year. Discussion A strength of the study is that it is a pragmatic trial which aims to recruit Maori using a Maori clinical team and protocol. It does not exclude people if English is not their first language. A potential limitation is the analysis of the results which is complex and may underestimate any effect if a large number of people refuse their consent in the group randomised to problem solving therapy as they will effectively cross over to the treatment as usual group. This study is the first randomised control trial to explicitly use cultural assessment and management. Trial

  15. Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy

    Science.gov (United States)

    Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

    2017-01-01

    , and the investigators will explain the study to the participants in detail. As an ethical clinical trial, the control group will also be given conventional cessation treatments, including NRT and counselling. Participants will be screened and provided with a registration number to protect their personal information. Informed consent will be obtained from the participants prior to enrolling them in the trial. Participants will be allowed to withdraw at anytime without penalty. Trial registration number ClinicalTrials.gov (NCT02768025); pre-results. PMID:28576892

  16. Describing qualitative research undertaken with randomised controlled trials in grant proposals: a documentary analysis

    Science.gov (United States)

    2014-01-01

    Background There is growing recognition of the value of conducting qualitative research with trials in health research. It is timely to reflect on how this qualitative research is presented in grant proposals to identify lessons for researchers and research commissioners. As part of a larger study focusing on how to maximise the value of undertaking qualitative research with trials, we undertook a documentary analysis of proposals of funded studies. Methods Using the metaRegister of Controlled Trials (mRCT) database we identified trials funded in the United Kingdom, ongoing between 2001 and 2010, and reporting the use of qualitative research. We requested copies of proposals from lead researchers. We extracted data from the proposals using closed and open questions, analysed using descriptive statistics and content analysis respectively. Results 2% (89/3812) of trials in the mRCT database described the use of qualitative research undertaken with the trial. From these 89 trials, we received copies of 36 full proposals, of which 32 met our inclusion criteria. 25% used less than a single paragraph to describe the qualitative research. The aims of the qualitative research described in these proposals focused mainly on the intervention or trial conduct. Just over half (56%) of the proposals included an explicit rationale for conducting the qualitative research with the trial, the most frequent being to optimise implementation into clinical practice or to interpret trial findings. Key information about methods, expertise and resources was missing in a large minority of proposals, in particular sample size, type of analysis, and non-personnel resources. 28% specifically stated that qualitative researchers would conduct the qualitative research. Conclusions Our review of proposals of successfully funded studies identified good practice but also identified limited space given to describing the qualitative research, with an associated lack of attention to the rationale for

  17. Potential risk for bacterial contamination in conventional reused ventilator systems and disposable closed ventilator-suction systems.

    Science.gov (United States)

    Li, Ya-Chi; Lin, Hui-Ling; Liao, Fang-Chun; Wang, Sing-Siang; Chang, Hsiu-Chu; Hsu, Hung-Fu; Chen, Sue-Hsien; Wan, Gwo-Hwa

    2018-01-01

    Few studies have investigated the difference in bacterial contamination between conventional reused ventilator systems and disposable closed ventilator-suction systems. The aim of this study was to investigate the bacterial contamination rates of the reused and disposable ventilator systems, and the association between system disconnection and bacterial contamination of ventilator systems. The enrolled intubated and mechanically ventilated patients used a conventional reused ventilator system and a disposable closed ventilator-suction system, respectively, for a week; specimens were then collected from the ventilator circuit systems to evaluate human and environmental bacterial contamination. The sputum specimens from patients were also analyzed in this study. The detection rate of bacteria in the conventional reused ventilator system was substantially higher than that in the disposable ventilator system. The inspiratory and expiratory limbs of the disposable closed ventilator-suction system had higher bacterial concentrations than the conventional reused ventilator system. The bacterial concentration in the heated humidifier of the reused ventilator system was significantly higher than that in the disposable ventilator system. Positive associations existed among the bacterial concentrations at different locations in the reused and disposable ventilator systems, respectively. The predominant bacteria identified in the reused and disposable ventilator systems included Acinetobacter spp., Bacillus cereus, Elizabethkingia spp., Pseudomonas spp., and Stenotrophomonas (Xan) maltophilia. Both the reused and disposable ventilator systems had high bacterial contamination rates after one week of use. Disconnection of the ventilator systems should be avoided during system operation to decrease the risks of environmental pollution and human exposure, especially for the disposable ventilator system. ClinicalTrials.gov PRS / NCT03359148.

  18. 46 CFR 78.17-5 - Valves and closing appliances.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Valves and closing appliances. 78.17-5 Section 78.17-5..., Drills, and Inspections § 78.17-5 Valves and closing appliances. (a) It shall be the duty of the master to see that all valves, including cross connecting valves where fitted, and other appliances such as...

  19. Method and apparatus for operating a powertrain system upon detecting a stuck-closed clutch

    Science.gov (United States)

    Hansen, R. Anthony

    2014-02-18

    A powertrain system includes a multi-mode transmission having a plurality of torque machines. A method for controlling the powertrain system includes identifying all presently applied clutches including commanded applied clutches and the stuck-closed clutch upon detecting one of the torque-transfer clutches is in a stuck-closed condition. A closed-loop control system is employed to control operation of the multi-mode transmission accounting for all the presently applied clutches.

  20. Patient-reported outcome (PRO assessment in clinical trials: a systematic review of guidance for trial protocol writers.

    Directory of Open Access Journals (Sweden)

    Melanie Calvert

    Full Text Available Evidence suggests there are inconsistencies in patient-reported outcome (PRO assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers.We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013 for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts. 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3% recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency.PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in

  1. Clinical Trials

    Medline Plus

    Full Text Available ... U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study explored whether the ...

  2. Designing clinical trials to assess antiepileptic drugs as monotherapy : difficulties and solutions.

    Science.gov (United States)

    Perucca, Emilio

    2008-01-01

    noninferiority trials, one of which has been completed and which led to approval of the monotherapy indication for levetiracetam in the EU. Noninferiority trials provide valuable data in a setting that most closely resembles routine clinical practice, but their interpretation can be complicated by uncertainties on assay sensitivity.Major evidence gaps in the treatment of epilepsy still remain and it is hoped that these will be addressed in the near future. High quality monotherapy trials are particularly needed to assess the comparative efficacy of older and newer drugs in less common epilepsy syndromes, including most generalized epilepsies, and to investigate the different treatment options in populations homogeneous not only in terms of syndromic classification, but also in terms of underlying aetiology and associated phenotypes.

  3. Closed forms and multi-moment maps

    DEFF Research Database (Denmark)

    Madsen, Thomas Bruun; Swann, Andrew Francis

    2013-01-01

    We extend the notion of multi-moment map to geometries defined by closed forms of arbitrary degree. We give fundamental existence and uniqueness results and discuss a number of essential examples, including geometries related to special holonomy. For forms of degree four, multi-moment maps are gu...

  4. 75 FR 74108 - Post Office Closing

    Science.gov (United States)

    2010-11-30

    ... the closing of the Eugene Post Office's University Station in Eugene, Oregon, has been filed. It... the Eugene Post Office's University Station located in Eugene, Oregon. The petition, which was filed.... Categories of issues apparently raised. The categories of issues raised include: Failure to follow the post...

  5. Defendants' Rights in Criminal Trials.

    Science.gov (United States)

    Martin, Ralph C., II; Keeley, Elizabeth

    1997-01-01

    Reviews the protections afforded by the Constitution for defendants in criminal trials. These include the right to a jury trial (in cases of possible incarceration), an impartial jury, and the requirement of a unanimous verdict. Defends the use of plea bargaining as essential to an efficient criminal justice system. (MJP)

  6. Complication rate in unprotected carotid artery stenting with closed-cell stents

    International Nuclear Information System (INIS)

    Tietke, Marc W.K.; Kerby, Tina; Alfke, Karsten; Riedel, Christian; Rohr, Axel; Jensen, Ulf; Jansen, Olaf; Zimmermann, Phillip; Stingele, Robert

    2010-01-01

    The discussion on the use of protection devices (PDs) in carotid artery stenting (CAS) is gaining an increasing role in lowering the periprocedural complication rates. While many reviews and reports with retrospective data analysis do promote the use of PDs the most recent multi-centre trials are showing advantages for unprotected CAS combined with closed-cell stent designs. We retrospectively analysed 358 unprotected CAS procedures performed from January 2003 to June 2009 in our clinic. Male/female ratio was 2.68/1. The average age was 69.3 years. Seventy-three percent (261/358) showed initial neurological symptoms. All patients were treated on a standardised interventional protocol. A closed and small-sized cell designed stent was implanted in most cases (85.2%). One hundred seventy-one (47.8%) were controlled by Doppler ultrasonography usually at first in a 3-month and later in 6-month intervals. The peri-interventional and 30-day mortality/stroke rate was 4.19% (15/358). These events included three deaths, five hyperperfusion syndromes (comprising one death by a secondary fatal intracranial haemorrhage), one subarachnoid haemorrhage and seven ischaemic strokes. Only 20% (3/15) of all complications occurred directly peri-interventional. The overall peri-interventional complication rate was 0.8% (3/358). Most complications occurred in initial symptomatic patients (5.36%). The in-stent restenosis rate for more than 70% was 7% (12/171) detected at an average of 9.8 month. Our clinical outcome demonstrates that unprotected CAS with small cell designed stents results in a very low procedural complication rate, which makes the use of a protection device dispensable. (orig.)

  7. Experimental simulation of closed timelike curves.

    Science.gov (United States)

    Ringbauer, Martin; Broome, Matthew A; Myers, Casey R; White, Andrew G; Ralph, Timothy C

    2014-06-19

    Closed timelike curves are among the most controversial features of modern physics. As legitimate solutions to Einstein's field equations, they allow for time travel, which instinctively seems paradoxical. However, in the quantum regime these paradoxes can be resolved, leaving closed timelike curves consistent with relativity. The study of these systems therefore provides valuable insight into nonlinearities and the emergence of causal structures in quantum mechanics--essential for any formulation of a quantum theory of gravity. Here we experimentally simulate the nonlinear behaviour of a qubit interacting unitarily with an older version of itself, addressing some of the fascinating effects that arise in systems traversing a closed timelike curve. These include perfect discrimination of non-orthogonal states and, most intriguingly, the ability to distinguish nominally equivalent ways of preparing pure quantum states. Finally, we examine the dependence of these effects on the initial qubit state, the form of the unitary interaction and the influence of decoherence.

  8. Patient representatives' views on patient information in clinical cancer trials.

    Science.gov (United States)

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-02-01

    Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I-III trials, randomized and non-randomized trials that evaluated chemotherapy/targeted therapy in the neoadjuvant, adjuvant and palliative settings. Data were collected through focus groups and were analysed using inductive content analysis. Two major themes emerged: emotional responses and cognitive responses. Subthemes related to the former included individual preferences and perceptions of effect, while subthemes related to the latter were comprehensibility and layout. Based on these observations the patient representatives provided suggestions for improvement, which largely included development of future simplified and more attractive informed consent forms. The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language, structured text and illustrations to improve the informed consent process and thereby patient enrolment into clinical trials.

  9. Internet interventions for chronic pain including headache: A systematic review

    Directory of Open Access Journals (Sweden)

    Monica Buhrman

    2016-05-01

    Full Text Available Chronic pain is a major health problem and behavioral based treatments have been shown to be effective. However, the availability of these kinds of treatments is scarce and internet-based treatments have been shown to be promising in this area. The objective of the present systematic review is to evaluate internet-based interventions for persons with chronic pain. The specific aims are to do an updated review with a broad inclusion of different chronic pain diagnoses and to assess disability and pain and also measures of catastrophizing, depression and anxiety. A systematic search identified 891 studies and 22 trials were selected as eligible for review. Two of the selected trials included children/youth and five included individuals with chronic headache and/or migraine. The most frequently measured domain reflected in the primary outcomes was interference/disability, followed by catastrophizing. Result across the studies showed a number of beneficial effects. Twelve trials reported significant effects on disability/interference outcomes and pain intensity. Positive effects were also found on psychological variable such as catastrophizing, depression and anxiety. Several studies (n = 12 were assessed to have an unclear level of risk bias. The attrition levels ranged from 4% to 54% where the headache trials had the highest drop-out levels. However, findings suggest that internet-based treatments based on cognitive behavioural therapy (CBT are efficacious measured with different outcome variables. Results are in line with trials in clinical settings. Meta-analytic statistics were calculated for interference/disability, pain intensity, catastrophizing and mood ratings. Results showed that the effect size for interference/disability was Hedge's g = −0.39, for pain intensity Hedge's g = −0.33, for catastrophizing Hedge's g = −0.49 and for mood variables (depression Hedge's g = −0.26.

  10. Methodology Series Module 4: Clinical Trials.

    Science.gov (United States)

    Setia, Maninder Singh

    2016-01-01

    In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

  11. On the limits of statistical learning: Intertrial contextual cueing is confined to temporally close contingencies.

    Science.gov (United States)

    Thomas, Cyril; Didierjean, André; Maquestiaux, François; Goujon, Annabelle

    2018-04-12

    Since the seminal study by Chun and Jiang (Cognitive Psychology, 36, 28-71, 1998), a large body of research based on the contextual-cueing paradigm has shown that the cognitive system is capable of extracting statistical contingencies from visual environments. Most of these studies have focused on how individuals learn regularities found within an intratrial temporal window: A context predicts the target position within a given trial. However, Ono, Jiang, and Kawahara (Journal of Experimental Psychology, 31, 703-712, 2005) provided evidence of an intertrial implicit-learning effect when a distractor configuration in preceding trials N - 1 predicted the target location in trials N. The aim of the present study was to gain further insight into this effect by examining whether it occurs when predictive relationships are impeded by interfering task-relevant noise (Experiments 2 and 3) or by a long delay (Experiments 1, 4, and 5). Our results replicated the intertrial contextual-cueing effect, which occurred in the condition of temporally close contingencies. However, there was no evidence of integration across long-range spatiotemporal contingencies, suggesting a temporal limitation of statistical learning.

  12. Study sponsorship and the nutrition research agenda: analysis of randomized controlled trials included in systematic reviews of nutrition interventions to address obesity.

    Science.gov (United States)

    Fabbri, Alice; Chartres, Nicholas; Scrinis, Gyorgy; Bero, Lisa A

    2017-05-01

    To categorize the research topics covered by a sample of randomized controlled trials (RCT) included in systematic reviews of nutrition interventions to address obesity; to describe their funding sources; and to explore the association between funding sources and nutrition research topics. Cross-sectional study. RCT included in Cochrane Reviews of nutrition interventions to address obesity and/or overweight. Two hundred and thirteen RCT from seventeen Cochrane Reviews were included. Funding source and authors' conflicts of interest were disclosed in 82·6 and 29·6 % of the studies, respectively. RCT were more likely to test an intervention to manipulate nutrients in the context of reduced energy intake (44·2 % of studies) than food-level (11·3 %) and dietary pattern-level (0·9 %) interventions. Most of the food industry-sponsored studies focused on interventions involving manipulations of specific nutrients (66·7 %). Only 33·1 % of the industry-funded studies addressed dietary behaviours compared with 66·9 % of the non-industry-funded ones (P=0·002). The level of food processing was poorly considered across all funding sources. The predominance of RCT examining nutrient-specific questions could limit the public health relevance of rigorous evidence available for systematic reviews and dietary guidelines.

  13. Accounting for multiple births in randomised trials: a systematic review.

    Science.gov (United States)

    Yelland, Lisa Nicole; Sullivan, Thomas Richard; Makrides, Maria

    2015-03-01

    Multiple births are an important subgroup to consider in trials aimed at reducing preterm birth or its consequences. Including multiples results in a unique mixture of independent and clustered data, which has implications for the design, analysis and reporting of the trial. We aimed to determine how multiple births were taken into account in the design and analysis of recent trials involving preterm infants, and whether key information relevant to multiple births was reported. We conducted a systematic review of multicentre randomised trials involving preterm infants published between 2008 and 2013. Information relevant to multiple births was extracted. Of the 56 trials included in the review, 6 (11%) excluded multiples and 24 (43%) failed to indicate whether multiples were included. Among the 26 trials that reported multiples were included, only one (4%) accounted for clustering in the sample size calculations and eight (31%) took the clustering into account in the analysis of the primary outcome. Of the 20 trials that randomised infants, 12 (60%) failed to report how infants from the same birth were randomised. Information on multiple births is often poorly reported in trials involving preterm infants, and clustering due to multiple births is rarely taken into account. Since ignoring clustering could result in inappropriate recommendations for clinical practice, clustering should be taken into account in the design and analysis of future neonatal and perinatal trials including infants from a multiple birth. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Trends in Canadian Respiratory Clinical Trials from 2001 to 2011

    Directory of Open Access Journals (Sweden)

    Claire Elizabeth Tacon

    2014-01-01

    Full Text Available Clinical research bridges patients’ unmet medical need with innovative medicines, increases knowledge acquisition by clinicians, and creates solutions to improve the sustainability and quality of the Canadian health care system and economy. The Canadian Institutes of Health Research and the Canadian Lung Association have recently raised concerns over declining research activities within the Canadian respiratory community. While there are currently >3000 ongoing clinical trials in Canada, the number of trials investigating common respiratory diseases is unknown. The objective of the present study was to monitor the trends in industry- and non-industry-sponsored respiratory clinical trials in Canada from 2001 to 2011. Trialtrove 2012 (Citeline, an Informa UK business, a database containing summarized clinical trial information regarding pharmaceutical products, was searched using common chronic respiratory disease terms: “allergic rhinitis”, “asthma”, “chronic obstructive pulmonary disease (COPD”, “cystic fibrosis”, “respiratory infections”, “pulmonary fibrosis” and “smoking cessation”. Over the past 10 years, the number of respiratory clinical trials conducted in Canada has increased (4.49 per year; P=0.004. From 2001 to 2011, the majority of trials were performed in asthma, followed closely by respiratory infections and COPD. Over the past decade, the number of trials investigating COPD and respiratory infections increased (P<0.05, while asthma trials showed a declining trend since 2007. Of the clinical trials performed during this 10-year period, the majority were in phase III, with a significant increase in the number of phase II trials (2.49 per year; P=0.008. However, certain trends observed are concerning and warrant further monitoring in the coming years.

  15. Including the Copenhagen Adduction Exercise in the FIFA 11+ Provides Missing Eccentric Hip Adduction Strength Effect in Male Soccer Players: A Randomized Controlled Trial.

    Science.gov (United States)

    Harøy, Joar; Thorborg, Kristian; Serner, Andreas; Bjørkheim, André; Rolstad, Linn E; Hölmich, Per; Bahr, Roald; Andersen, Thor Einar

    2017-11-01

    The FIFA 11+ was developed as a complete warm-up program to prevent injuries in soccer players. Although reduced hip adduction strength is associated with groin injuries, none of the exercises included in the FIFA 11+ seem to specifically target hip adduction strength. To investigate the effect on eccentric hip adduction strength of the FIFA 11+ warm-up program with or without the Copenhagen adduction exercise. Randomized controlled trial; Level of evidence, 1. We recruited 45 eligible players from 2 U19 elite male soccer teams. Players were randomized into 2 groups; 1 group carried out the standard FIFA 11+ program, while the other carried out the FIFA 11+ but replaced the Nordic hamstring exercise with the Copenhagen adduction exercise. Both groups performed the intervention 3 times weekly for 8 weeks. Players completed eccentric strength and sprint testing before and after the intervention. Per-protocol analyses were performed, and 12 players were excluded due to low compliance (<67% of sessions completed). The main outcome was eccentric hip adduction strength (N·m/kg). Between-group analyses revealed a significantly greater increase in eccentric hip adduction strength of 0.29 Nm/kg (8.9%; P = .01) in favor of the group performing the Copenhagen adduction exercise, whereas no within-group change was noted in the group that used the standard FIFA 11+ program (-0.02 N·m/kg [-0.7%]; P = .69). Including the Copenhagen adduction exercise in the FIFA 11+ program increases eccentric hip adduction strength, while the standard FIFA 11+ program does not. Registration: Registration: ISRCTN13731446 (International Standard Randomised Controlled Trial Number registry).

  16. Spasm of accommodation associated with closed head trauma.

    Science.gov (United States)

    Chan, R V Paul; Trobe, Jonathan D

    2002-03-01

    Spasm of accommodation, creating pseudomyopia, is generally associated with miosis and excess convergence as part of spasm of the near reflex. It may also exist as an isolated entity, usually attributed to psychogenic causes. We present six cases of accommodative spasm associated with closed head injury. All patients were male, ranging in age between 16 and 37 years. The degree of pseudomyopia, defined as the difference between manifest and cycloplegic refraction, was 1.5 to 2 diopters. A 3-year trial of pharmacologically induced cycloplegia in one patient did not lead to reversal of the spasm when the cycloplegia was stopped. All patients required the manifest refraction to see clearly at distance. The pseudomyopia endured for at least 7 years following head trauma. This phenomenon may represent traumatic activation or disinhibition of putative brain stem accommodation centers in young individuals.

  17. Sustainable development of a GCP-compliant clinical trials platform in Africa: the malaria clinical trials alliance perspective.

    Science.gov (United States)

    Ogutu, Bernhards R; Baiden, Rita; Diallo, Diadier; Smith, Peter G; Binka, Fred N

    2010-04-20

    The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that

  18. Off-label psychopharmacologic prescribing for children: History supports close clinical monitoring

    Directory of Open Access Journals (Sweden)

    Fegert Joerg M

    2008-09-01

    Full Text Available Abstract The review presents pediatric adverse drug events from a historical perspective and focuses on selected safety issues associated with off-label use of medications for the psychiatric treatment of youth. Clinical monitoring procedures for major psychotropic drug classes are reviewed. Prior studies suggest that systematic treatment monitoring is warranted so as to both minimize risk of unexpected adverse events and exposures to ineffective treatments. Clinical trials to establish the efficacy and safety of drugs currently being used off-label in the pediatric population are needed. In the meantime, clinicians should consider the existing evidence-base for these drugs and institute close clinical monitoring.

  19. Efficient design of clinical trials and epidemiological research: is it possible?

    Science.gov (United States)

    Lauer, Michael S; Gordon, David; Wei, Gina; Pearson, Gail

    2017-08-01

    Randomized clinical trials and large-scale, cohort studies continue to have a critical role in generating evidence in cardiovascular medicine; however, the increasing concern is that ballooning costs threaten the clinical trial enterprise. In this Perspectives article, we discuss the changing landscape of clinical research, and clinical trials in particular, focusing on reasons for the increasing costs and inefficiencies. These reasons include excessively complex design, overly restrictive inclusion and exclusion criteria, burdensome regulations, excessive source-data verification, and concerns about the effect of clinical research conduct on workflow. Thought leaders have called on the clinical research community to consider alternative, transformative business models, including those models that focus on simplicity and leveraging of digital resources. We present some examples of innovative approaches by which some investigators have successfully conducted large-scale, clinical trials at relatively low cost. These examples include randomized registry trials, cluster-randomized trials, adaptive trials, and trials that are fully embedded within digital clinical care or administrative platforms.

  20. Engine including hydraulically actuated valvetrain and method of valve overlap control

    Science.gov (United States)

    Cowgill, Joel [White Lake, MI

    2012-05-08

    An exhaust valve control method may include displacing an exhaust valve in communication with the combustion chamber of an engine to an open position using a hydraulic exhaust valve actuation system and returning the exhaust valve to a closed position using the hydraulic exhaust valve actuation assembly. During closing, the exhaust valve may be displaced for a first duration from the open position to an intermediate closing position at a first velocity by operating the hydraulic exhaust valve actuation assembly in a first mode. The exhaust valve may be displaced for a second duration greater than the first duration from the intermediate closing position to a fully closed position at a second velocity at least eighty percent less than the first velocity by operating the hydraulic exhaust valve actuation assembly in a second mode.

  1. Comparison of mailed invitation strategies to improve fecal occult blood test participation in men: protocol for a randomized controlled trial.

    Science.gov (United States)

    Duncan, Amy; Zajac, Ian; Flight, Ingrid; Stewart, Benjamin J R; Wilson, Carlene; Turnbull, Deborah

    2013-07-31

    Men have a significantly increased risk of being diagnosed with, and dying from, colorectal cancer (CRC) than women. Men also participate in fecal occult blood test (FOBT) screening at a lower rate than women. This study will determine whether strategies that target men's attitudes toward screening, and matched to stage of readiness to screen, increase men's FOBT participation compared to a standard approach. Eligible trial participants will be a national sample of 9,200 men aged 50 to 74 years, living in urban Australia and randomly selected from the Australian electoral roll. Trial participants will be mailed an advance notification letter, followed 2 weeks later by an invitation letter and a free fecal immunochemical test (FIT) kit. The intervention is a factorial design, randomized controlled trial (RCT) with four trial arms, including a control. The content of the advance notification and invitation letters will differ by trial arm as follows: 1) standard advance notification and standard invitation (control arm); 2) targeted advance notification and standard invitation; 3) standard advance notification and targeted invitation; and 4) targeted advance notification and targeted invitation. The standard letters will replicate as closely as possible the letters included in the Australian National Bowel Cancer Screening Program (NBCSP). Modified advance notification and invitation letters will incorporate additional messages to target men in the precontemplation (advance notification) and contemplation stages (invitation). The primary outcome is return of the completed FIT within 12 weeks of invitation. Analysts will be blinded to trial assignment and participants will be blinded to the use of varying invitational materials. Subsamples from each trial arm will complete baseline and endpoint surveys to measure the psychological impact of the intervention, and qualitative interviews will be conducted to evaluate attitudes toward the intervention. The outcomes of

  2. Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.

    Science.gov (United States)

    Massett, Holly A; Mishkin, Grace; Rubinstein, Larry; Ivy, S Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A; Abrams, Jeffrey S

    2016-11-15

    Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397. ©2016 American Association for Cancer Research.

  3. Real-time enrollment dashboard for multisite clinical trials

    Directory of Open Access Journals (Sweden)

    William A. Mattingly

    2015-10-01

    Conclusion: We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are useful for clinical trial management. They can be used in a standalone trial or can be included into a larger management system.

  4. A systematic review of the use of an expertise-based randomised controlled trial design.

    Science.gov (United States)

    Cook, Jonathan A; Elders, Andrew; Boachie, Charles; Bassinga, Ted; Fraser, Cynthia; Altman, Doug G; Boutron, Isabelle; Ramsay, Craig R; MacLennan, Graeme S

    2015-05-30

    Under a conventional two-arm randomised trial design, participants are allocated to an intervention and participating health professionals are expected to deliver both interventions. However, health professionals often have differing levels of expertise in a skill-based interventions such as surgery or psychotherapy. An expertise-based approach to trial design, where health professionals only deliver an intervention in which they have expertise, has been proposed as an alternative. The aim of this project was to systematically review the use of an expertise-based trial design in the medical literature. We carried out a comprehensive search of nine databases--AMED, BIOSIS, CENTRAL, CINAHL, Cochrane Methodology Register, EMBASE, MEDLINE, Science Citation Index, and PsycINFO--from 1966 to 2012 and performed citation searches using the ISI Citation Indexes and Scopus. Studies that used an expertise-based trial design were included. Two review authors independently screened the titles and abstracts and assessed full-text reports. Data were extracted and summarised on the study characteristics, general and expertise-specific study methodology, and conduct. In total, 7476 titles and abstracts were identified, leading to 43 included studies (54 articles). The vast majority (88%) used a pure expertise-based design; three (7%) adopted a hybrid design, and two (5%) used a design that was unclear. Most studies compared substantially different interventions (79%). In many cases, key information relating to the expertise-based design was absent; only 12 (28%) reported criteria for delivering both interventions. Most studies recruited the target sample size or very close to it (median of 101, interquartile range of 94 to 118), although the target was reported for only 40% of studies. The proportion of participants who received the allocated intervention was high (92%, interquartile range of 82 to 99%). While use of an expertise-based trial design is growing, it remains uncommon

  5. 77 FR 6867 - Practice Guide for Proposed Trial Rules

    Science.gov (United States)

    2012-02-09

    ... new trial proceedings to be conducted by the Patent Trial and Appeal Board (Board) including inter... conducted by the Board including: (1) Inter partes review (IPR); (2) post-grant review (PGR); (3) a... response to the petition, including a simple statement that patent owner elects not to respond to the...

  6. Interpersonal Mindfulness Informed by Functional Analytic Psychotherapy: Findings from a Pilot Randomized Trial

    Science.gov (United States)

    Bowen, Sarah; Haworth, Kevin; Grow, Joel; Tsai, Mavis; Kohlenberg, Robert

    2012-01-01

    Functional Analytic Psychotherapy (FAP; Kohlenberg & Tsai, 1991) aims to improve interpersonal relationships through skills intended to increase closeness and connection. The current trial assessed a brief mindfulness-based intervention informed by FAP, in which an interpersonal element was added to a traditional intrapersonal mindfulness…

  7. Multiple-level stakeholder engagement in malaria clinical trials: addressing the challenges of conducting clinical research in resource-limited settings.

    Science.gov (United States)

    Mtove, George; Kimani, Joshua; Kisinza, William; Makenga, Geofrey; Mangesho, Peter; Duparc, Stephan; Nakalembe, Miriam; Phiri, Kamija S; Orrico, Russell; Rojo, Ricardo; Vandenbroucke, Pol

    2018-03-22

    Multinational clinical trials are logistically complex and require close coordination between various stakeholders. They must comply with global clinical standards and are accountable to multiple regulatory and ethical bodies. In resource-limited settings, it is challenging to understand how to apply global clinical standards to international, national, and local factors in clinical trials, making multiple-level stakeholder engagement an important element in the successful conduct of these clinical trials. During the planning and implementation of a large multinational clinical trial for intermittent preventive treatment of malaria in pregnancy in resource-limited areas of sub-Saharan Africa, we encountered numerous challenges, which required implementation of a range of engagement measures to ensure compliance with global clinical and regulatory standards. These challenges included coordination with ongoing global malaria efforts, heterogeneity in national regulatory structures, sub-optimal healthcare infrastructure, local practices and beliefs, and perspectives that view healthcare providers with undue trust or suspicion. In addition to engagement with international bodies, such as the World Health Organization, the Malaria in Pregnancy Consortium, the Steve Biko Centre for Bioethics, and the London School of Hygiene and Tropical Medicine, in order to address the challenges just described, Pfizer Inc. and Medicines for Malaria Venture (the "Sponsoring Entities" for these studies) and investigators liaised with national- and district-level stakeholders such as health ministers and regional/local community health workers. Community engagement measures undertaken by investigators included local meetings with community leaders to explain the research aims and answer questions and concerns voiced by the community. The investigators also engaged with family members of prospective trial participants in order to be sensitive to local practices and beliefs. Engagement

  8. Closing the achievement gap through modification of neurocognitive and neuroendocrine function: results from a cluster randomized controlled trial of an innovative approach to the education of children in kindergarten.

    Directory of Open Access Journals (Sweden)

    Clancy Blair

    Full Text Available Effective early education is essential for academic achievement and positive life outcomes, particularly for children in poverty. Advances in neuroscience suggest that a focus on self-regulation in education can enhance children's engagement in learning and establish beneficial academic trajectories in the early elementary grades. Here, we experimentally evaluate an innovative approach to the education of children in kindergarten that embeds support for self-regulation, particularly executive functions, into literacy, mathematics, and science learning activities. Results from a cluster randomized controlled trial involving 29 schools, 79 classrooms, and 759 children indicated positive effects on executive functions, reasoning ability, the control of attention, and levels of salivary cortisol and alpha amylase. Results also demonstrated improvements in reading, vocabulary, and mathematics at the end of kindergarten that increased into the first grade. A number of effects were specific to high-poverty schools, suggesting that a focus on executive functions and associated aspects of self-regulation in early elementary education holds promise for closing the achievement gap.

  9. Closing the achievement gap through modification of neurocognitive and neuroendocrine function: results from a cluster randomized controlled trial of an innovative approach to the education of children in kindergarten.

    Science.gov (United States)

    Blair, Clancy; Raver, C Cybele

    2014-01-01

    Effective early education is essential for academic achievement and positive life outcomes, particularly for children in poverty. Advances in neuroscience suggest that a focus on self-regulation in education can enhance children's engagement in learning and establish beneficial academic trajectories in the early elementary grades. Here, we experimentally evaluate an innovative approach to the education of children in kindergarten that embeds support for self-regulation, particularly executive functions, into literacy, mathematics, and science learning activities. Results from a cluster randomized controlled trial involving 29 schools, 79 classrooms, and 759 children indicated positive effects on executive functions, reasoning ability, the control of attention, and levels of salivary cortisol and alpha amylase. Results also demonstrated improvements in reading, vocabulary, and mathematics at the end of kindergarten that increased into the first grade. A number of effects were specific to high-poverty schools, suggesting that a focus on executive functions and associated aspects of self-regulation in early elementary education holds promise for closing the achievement gap.

  10. Methodology series module 4: Clinical trials

    Directory of Open Access Journals (Sweden)

    Maninder Singh Setia

    2016-01-01

    Full Text Available In a clinical trial, study participants are (usually divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care. We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1 parallel study design, (2 cross-over design, (3 factorial design, and (4 withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials. Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

  11. Short evaluations on hydroponic systems with closed cycle; Prime valutazioni su sistemi idroponici a ciclo chiuso

    Energy Technology Data Exchange (ETDEWEB)

    Martignon, G [ENEL DSR, Centro Ricerche Ambiente e Materiali, Milan (Italy); Venezia, A [MIRAAF, Istituto Sperimentale per l` Orticultura (Italy) Sezione di Montanaso Lombardo

    1996-01-01

    In the experimental station at Tavazzano from 1993 to 1995 several trials were carried out growing vegetables, cut flowers and ornamental species with soil less culture. Different soil less techniques were utilized (on substrate in begs with open system; NFT, Ebb-Flood, sub irrigation on substrate in pot with closed system). The results obtained till now give the possibility to make some comments about management and problems of the soil less systems. The paper shows aspects related to the management of plant nutrition (nutrient solution, irrigation, substrates)and to fruit or flower production. The environmental effects of the different closed soil less culture systems tested are described, with respect to the cultivation on substrate in beg with open system, still generally utilized.

  12. Predictive event modelling in multicenter clinical trials with waiting time to response.

    Science.gov (United States)

    Anisimov, Vladimir V

    2011-01-01

    A new analytic statistical technique for predictive event modeling in ongoing multicenter clinical trials with waiting time to response is developed. It allows for the predictive mean and predictive bounds for the number of events to be constructed over time, accounting for the newly recruited patients and patients already at risk in the trial, and for different recruitment scenarios. For modeling patient recruitment, an advanced Poisson-gamma model is used, which accounts for the variation in recruitment over time, the variation in recruitment rates between different centers and the opening or closing of some centers in the future. A few models for event appearance allowing for 'recurrence', 'death' and 'lost-to-follow-up' events and using finite Markov chains in continuous time are considered. To predict the number of future events over time for an ongoing trial at some interim time, the parameters of the recruitment and event models are estimated using current data and then the predictive recruitment rates in each center are adjusted using individual data and Bayesian re-estimation. For a typical scenario (continue to recruit during some time interval, then stop recruitment and wait until a particular number of events happens), the closed-form expressions for the predictive mean and predictive bounds of the number of events at any future time point are derived under the assumptions of Markovian behavior of the event progression. The technique is efficiently applied to modeling different scenarios for some ongoing oncology trials. Case studies are considered. Copyright © 2011 John Wiley & Sons, Ltd.

  13. Comparison between autologous blood transfusion drainage and closed-suction drainage/no drainage in total knee arthroplasty: a meta-analysis.

    Science.gov (United States)

    Hong, Kun-Hao; Pan, Jian-Ke; Yang, Wei-Yi; Luo, Ming-Hui; Xu, Shu-Chai; Liu, Jun

    2016-08-01

    Autologous blood transfusion (ABT) drainage system is a new unwashed salvaged blood retransfusion system for total knee replacement (TKA). However, whether to use ABT drainage, closed-suction (CS) drainage or no drainage in TKA surgery remains controversial. This is the first meta-analysis to assess the clinical efficiency, safety and potential advantages regarding the use of ABT drains compared with closed-suction/no drainage. PubMed, Embase, and the Cochrane Library were comprehensively searched in March 2015. Fifteen randomized controlled trials (RCTs) were identified and pooled for statistical analysis. The primary outcome evaluated was homologous blood transfusion rate. The secondary outcomes were post-operative haemoglobin on days 3-5, length of hospital stay and wound infections after TKA surgery. The pooled data included 1,721 patients and showed that patients in the ABT drainage group might benefit from lower blood transfusion rates (16.59 % and 37.47 %, OR: 0.28 [0.14, 0.55]; 13.05 % and 16.91 %, OR: 0.73 [0.47,1.13], respectively). Autologous blood transfusion drainage and closed-suction drainage/no drainage have similar clinical efficacy and safety with regard to post-operative haemoglobin on days 3-5, length of hospital stay and wound infections. Autologous blood transfusion drainage offers a safe and efficient alternative to CS/no drainage with a lower blood transfusion rate. Future large-volume high-quality RCTs with extensive follow-up will affirm and update this system review.

  14. Variational functionals which admit discontinuous trial functions

    International Nuclear Information System (INIS)

    Nelson, P. Jr.

    1975-01-01

    It is argued that variational synthesis with discontinuous trial functions requires variational principles applicable to equations involving operators acting between distinct Hilbert spaces. A description is given of a Roussopoulos-type variational principle generalized to cover this situation. This principle is suggested as the basis for a unified approach to the derivation of variational functionals. In addition to esthetics, this approach has the advantage that the mathematical details increase the understanding of the derived functional, particularly the sense in which a synthesized solution should be regarded as an approximation to the true solution. By way of illustration, the generalized Roussopoulos principle is applied to derive a class of first-order diffusion functionals which admit trial functions containing approximations at an interface. These ''asymptotic'' interface quantities are independent of the limiting approximations from either side and permit use of different trial spectra at and on either side of an interface. The class of functionals derived contains as special cases both the Lagrange multiplier method of Buslik and two functionals of Lambropoulos and Luco. Some numerical results for a simple two-group model confirm that the ''multipliers'' can closely approximate the appropriate quantity in the region near an interface. (U.S.)

  15. Reduced dietary sodium intake increases heart rate. A meta-analysis of 63 randomized controlled trials including 72 study populations.

    Directory of Open Access Journals (Sweden)

    Niels eGraudal

    2016-03-01

    Full Text Available Reduced dietary sodium intake (sodium reduction increases heart rate in some studies of animals and humans. As heart rate is independently associated with the development of heart failure and increased risk of premature death a potential increase in heart rate could be a harmful side-effect of sodium reduction. The purpose of the present meta-analysis was to investigate the effect of sodium reduction on heart rate. Relevant studies were retrieved from an updated pool of 176 randomized controlled trials (RCTs published in the period 1973–2014. 63 of the RCTs including 72 study populations reported data on heart rate. In a meta-analysis of these data sodium reduction increased heart rate with 1.65 beats per minute [95% CI: 1.19, 2.11], p < 0.00001, corresponding to 2.4% of the baseline heart rate. This effect was independent of baseline blood pressure. In conclusion sodium reduction increases heart rate by as much (2.4% as it decreases blood pressure (2.5%. This side-effect, which may cause harmful health effects, contributes to the need for a revision of the present dietary guidelines.

  16. Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative.

    Science.gov (United States)

    Huang, Grant D; Bull, Jonca; Johnston McKee, Kelly; Mahon, Elizabeth; Harper, Beth; Roberts, Jamie N

    2018-03-01

    Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  17. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

    Science.gov (United States)

    Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

    2015-05-01

    The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  18. Trial sponsorship and self-reported conflicts of interest in breast cancer radiation therapy: An analysis of prospective clinical trials.

    Science.gov (United States)

    Leite, Elton T T; Moraes, Fabio Y; Marta, Gustavo N; Taunk, Neil K; Vieira, Marina T L; Hanna, Samir A; Silva, João Luis F; Carvalho, Heloisa A

    2017-06-01

    We aim to assess any association between study and self-reported conflict of interest (COI) or trial sponsorship in breast cancer radiation clinical trials. We searched PubMed for all clinical trials (CTs) published between 09/2004 and 09/2014 related to breast cancer. We included only radiotherapy CTs with primary clinical endpoints. We classified eligible trials according to the funding source, presence or absence of conflict of interest, study conclusion and impact factor (IF). 1,603 CTs were retrieved. 72 randomized clinical trials were included for analysis. For-profit (PO), not for profit organization (nPO), none and not reported sponsorship rates were 9/72 (12.5%), 35/72 (48.6%), 1/72 (1.4%), 27/72 (37.5%), respectively. Present, absent or not reported COI were found in 6/72 (8.3%), 43/72 (59.7%) and 23/72 (32%) of the CTs, respectively. Conclusion was positive, neutral and negative in 57/72 (79.1%), 9/72 (12.5%) and 6/72 (8.4%) of the trials, respectively. Positive conclusion was reported in 33/44 (75%) funded trials (PO and nPO) and 5/6 (83.3%) CTs with reported COI. On univariate analysis no association with funding source (P=0.178), COI (P=0.678) or trial region (P=0.567) and trial positive conclusion was found. Sponsored trials (HR 4.50, 95CI-0.1.23-16.53;P=0.0023) and positive trials (HR 4.78, 95CI- 1.16-19.63;P=0.030) were more likely to be published in higher impact factor journals in the multivariate analysis. nPO funding was reported in almost 50% of the evaluated CTs. No significant association between study conclusion and funding source, COI or trial region was identified. Sponsored trials and positive trials were more likely to be published in higher impact factor journals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The Trial

    Science.gov (United States)

    Bryant, Jen

    2004-01-01

    Growing up in Flemington, New Jersey, put Jen Bryant in the heart of the lore behind the Lindbergh baby kidnapping. Family stories of the events of the day and extensive research led to "The Trial," a novel in verse. The first several parts of this novel are included here.

  20. Clinical Trials

    Medline Plus

    Full Text Available ... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... include factors such as a patient's age and gender, the type and stage of disease, ... helps ensure that any differences observed during a trial are due to the ...

  1. Cancer clinical trials

    International Nuclear Information System (INIS)

    Scheurlen, A.; Kay, R.; Baum, M.

    1988-01-01

    This book contains the proceedings on Cancer clinical trials: A critical appraisal. Topics covered include: Scientific fundamentals; Heterogeneous treatment effects; On combining information: Historical controls, overviews, and comprehensive cohort studies; and assessment of quality of life

  2. Reporting of conflicts of interest from drug trials in Cochrane reviews: cross sectional study.

    Science.gov (United States)

    Roseman, Michelle; Turner, Erick H; Lexchin, Joel; Coyne, James C; Bero, Lisa A; Thombs, Brett D

    2012-08-16

    To investigate the degree to which Cochrane reviews of drug interventions published in 2010 reported conflicts of interest from included trials and, among reviews that reported this information, where it was located in the review documents. Cross sectional study. Cochrane Database of Systematic Reviews. Systematic reviews of drug interventions published in 2010 in the Cochrane Database of Systematic Reviews, with review content classified as up to date in 2008 or later and with results from one or more randomised controlled trials. Of 151 included Cochrane reviews, 46 (30%, 95% confidence interval 24% to 38%) reported information on the funding sources of included trials, including 30 (20%, 14% to 27%) that reported information on trial funding for all included trials and 16 (11%, 7% to 17%) that reported for some, but not all, trials. Only 16 of the 151 Cochrane reviews (11%, 7% to 17%) provided any information on trial author-industry financial ties or trial author-industry employment. Information on trial funding and trial author-industry ties was reported in one to seven locations within each review, with no consistent reporting location observed. Most Cochrane reviews of drug trials published in 2010 did not provide information on trial funding sources or trial author-industry financial ties or employment. When this information was reported, location of reporting was inconsistent across reviews.

  3. Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients: a position paper endorsed by ESMINT and ESNR. Pt. 1. Current situation and major research questions

    Energy Technology Data Exchange (ETDEWEB)

    Fiehler, Jens [University Medical Centre Hamburg-Eppendorf, Department of Neuroradiology, Hamburg (Germany); Soederman, Michael [Karolinska University Hospital, Department of Neuroradiology, Stockholm (Sweden); Turjman, Francis [Hopital Neurologique, Centre de Neurosciences Cognitives, Department of Neuroradiology, Lyon (France); White, Philip M. [Western General Hospital, University of Edinburgh, Department of Clinical Neurosciences, Edinburgh (United Kingdom); Bakke, Soeren Jacob [Oslo University Hospital, Rikshospitalet, Department of Neuroradiology, Oslo (Norway); Mangiafico, Salvatore [University Hospital Careggi, Interventional Neuroradiology Unit, Florence (Italy); Kummer, Ruediger von [University of Dresden, Department of Neuroradiology, Dresden (Germany); Muto, Mario [University of Naples, Department of Neuroradiology, Naples (Italy); Cognard, Christophe [Hopital Purpan, Service de Neuroradiologie, Toulouse (France); Gralla, Jan [Inselspital Bern, Department of Neuroradiology, Bern (Switzerland)

    2012-12-15

    A new era of stroke treatment may have begun with mechanical thrombectomy (MT) by fully deployed closed-cell self-expanding stents (stent-triever). Multiple case series and the first randomised controlled trials (RCTs) have now been published. More studies are under way involving large numbers of patients, which in turn has resulted in less strict ''pragmatic'' study protocols. Problems with current trials include a lack of standardisation in the conduct of the recanalisation procedure, the definition of primary endpoints such as the grade of arterial recanalisation and tissue reperfusion, and the post-surgical care provided. In Part 1 of this two part series, we outline the current situation and the major research questions. (orig.)

  4. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters

    Directory of Open Access Journals (Sweden)

    Carolina L. Haass-Koffler

    2017-12-01

    Full Text Available The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled “Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers” (Haass-Koffler et al., 2017 [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73. Keywords: Glutamate receptor subtype 5 (mGlu5, Allosteric modulator, GET 73, Safety, Tolerability

  5. Multitarget multisensor closed-loop tracking

    Science.gov (United States)

    Sanders-Reed, John N.

    2004-07-01

    This paper describes a closed-loop tracking system using multiple co-located sensors to develop multi-sensor track histories on multiple targets. The use of multiple, co-aligned sensors to track multiple, possibly maneuvering targets, presents a number of tracker design challenges and opportunities. Many of these problems have been addressed individually in the published literature from a theoretical point of view. However, no one has yet addressed the design and implementation of a specific tracker to meet all of these requirements at once. Specific questions addressed in this paper include how to assign N detections in a current frame to M active tracks, how to initiate new tracks and terminate dead tracks, how to combine information from multiple sensors into a single integrated picture, represented by a global track file, and how to perform these functions in a timely manner to support a precision closed loop tracking system.

  6. Efficacy determinants of subcutaneous microdose glucagon during closed-loop control.

    Science.gov (United States)

    Russell, Steven J; El-Khatib, Firas H; Nathan, David M; Damiano, Edward R

    2010-11-01

    During a previous clinical trial of a closed-loop blood glucose (BG) control system that administered insulin and microdose glucagon subcutaneously, glucagon was not uniformly effective in preventing hypoglycemia (BGMicrodose glucagon administration was relatively ineffective in preventing hypoglycemia when plasma insulin levels exceeded the controller's online estimate by >60%. After the algorithm PK parameters were globally adjusted, insulin dosing was more conservative and microdose glucagon administration was very effective in reducing hypoglycemia while maintaining normal plasma glucagon levels. Improvements in the accuracy of the controller's online estimate of plasma insulin levels could be achieved if ultrarapid-acting insulin formulations could be developed with faster absorption and less intra- and intersubject variability than the current insulin analogs available today. © 2010 Diabetes Technology Society.

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

    Science.gov (United States)

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

    2017-10-18

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

  8. RTOG: Updated results of randomized trials

    International Nuclear Information System (INIS)

    Curran, Walter J.

    1997-01-01

    Objective: To review the background, rationale and available results for recently completed randomized comparative clinical trials of the Radiation Therapy Oncology Group (RTOG), including inter group trials in which the RTOG has been the managing group or a major participant. When available, laboratory studies will be correlated with clinical results

  9. Close Binaries in the 21st Century: New Opportunities and Challenges

    CERN Document Server

    Giménez, Àlvaro; Niarchos, Panagiotis; Rucinski, Slavek

    2006-01-01

    An International Conference entitled "Close Binaries in the 21st Century: New Opportunities and Challenges", was held in Syros island, Greece, from 27 to 30 June, 2005. There are many binary star systems whose components are so close together, that they interact in various ways. Stars in such systems do not pass through all stages of their evolution independently of each other; in fact their evolutionary path is significantly affected by their companions. Processes of interaction include gravitational effects, mutual irradiation, mass exchange, mass loss from the system, phenomena of extended atmospheres, semi-transparent atmospheric clouds, variable thickness disks and gas streams. The zoo of Close Binary Systems includes: Close Eclipsing Binaries (Detached, Semi-detached, Contact), High and Low-Mass X-ray Binaries, Cataclysmic Variables, RS CVn systems, Pulsar Binaries and Symbiotic Stars. The study of these binaries triggered the development of new branches of astrophysics dealing with the structure and ev...

  10. Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain

    Directory of Open Access Journals (Sweden)

    Prasad Shirvalkar

    2018-03-01

    Full Text Available Pain is a subjective experience that alerts an individual to actual or potential tissue damage. Through mechanisms that are still unclear, normal physiological pain can lose its adaptive value and evolve into pathological chronic neuropathic pain. Chronic pain is a multifaceted experience that can be understood in terms of somatosensory, affective, and cognitive dimensions, each with associated symptoms and neural signals. While there have been many attempts to treat chronic pain, in this article we will argue that feedback-controlled ‘closed-loop’ deep brain stimulation (DBS offers an urgent and promising route for treatment. Contemporary DBS trials for chronic pain use “open-loop” approaches in which tonic stimulation is delivered with fixed parameters to a single brain region. The impact of key variables such as the target brain region and the stimulation waveform is unclear, and long-term efficacy has mixed results. We hypothesize that chronic pain is due to abnormal synchronization between brain networks encoding the somatosensory, affective and cognitive dimensions of pain, and that multisite, closed-loop DBS provides an intuitive mechanism for disrupting that synchrony. By (1 identifying biomarkers of the subjective pain experience and (2 integrating these signals into a state-space representation of pain, we can create a predictive model of each patient's pain experience. Then, by establishing how stimulation in different brain regions influences individual neural signals, we can design real-time, closed-loop therapies tailored to each patient. While chronic pain is a complex disorder that has eluded modern therapies, rich historical data and state-of-the-art technology can now be used to develop a promising treatment.

  11. Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy.

    Science.gov (United States)

    Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

    2017-06-02

    participants in detail. As an ethical clinical trial, the control group will also be given conventional cessation treatments, including NRT and counselling. Participants will be screened and provided with a registration number to protect their personal information. Informed consent will be obtained from the participants prior to enrolling them in the trial. Participants will be allowed to withdraw at anytime without penalty. ClinicalTrials.gov (NCT02768025); pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. High rate reactive sputtering in an opposed cathode closed-field unbalanced magnetron sputtering system

    Science.gov (United States)

    Sproul, William D.; Rudnik, Paul J.; Graham, Michael E.; Rohde, Suzanne L.

    1990-01-01

    Attention is given to an opposed cathode sputtering system constructed with the ability to coat parts with a size up to 15 cm in diameter and 30 cm in length. Initial trials with this system revealed very low substrate bias currents. When the AlNiCo magnets in the two opposed cathodes were arranged in a mirrored configuration, the plasma density at the substrate was low, and the substrate bias current density was less than 1 mA/sq cm. If the magnets were arranged in a closed-field configuration where the field lines from one set of magnets were coupled with the other set, the substrate bias current density was as high as 5.7 mA/sq cm when NdFeB magnets were used. In the closed-field configuration, the substrate bias current density was related to the magnetic field strength between the two cathodes and to the sputtering pressure. Hard well-adhered TiN coatings were reactively sputtered in the opposed cathode system in the closed-field configuration, but the mirrored configuration produced films with poor adhesion because of etching problems and low plasma density at the substrate.

  13. Permitting patients to pay for participation in clinical trials: the advent of the P4 trial.

    Science.gov (United States)

    Shaw, David; de Wert, Guido; Dondorp, Wybo; Townend, David; Bos, Gerard; van Gelder, Michel

    2017-06-01

    In this article we explore the ethical issues raised by permitting patients to pay for participation (P4) in clinical trials, and discuss whether there are any categorical objections to this practice. We address key considerations concerning payment for participation in trials, including patient autonomy, risk/benefit and justice, taking account of two previous critiques of the ethics of P4. We conclude that such trials could be ethical under certain strict conditions, but only if other potential sources of funding have first been explored or are unavailable.

  14. Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

    Science.gov (United States)

    Sivaramakrishnan, Gowri; Sridharan, Kannan

    2016-06-01

    Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be

  15. A water-based training program that include perturbation exercises to improve stepping responses in older adults: study protocol for a randomized controlled cross-over trial

    Directory of Open Access Journals (Sweden)

    Tsedek Irit

    2008-08-01

    Full Text Available Abstract Background Gait and balance impairments may increase the risk of falls, the leading cause of accidental death in the elderly population. Fall-related injuries constitute a serious public health problem associated with high costs for society as well as human suffering. A rapid step is the most important protective postural strategy, acting to recover equilibrium and prevent a fall from initiating. It can arise from large perturbations, but also frequently as a consequence of volitional movements. We propose to use a novel water-based training program which includes specific perturbation exercises that will target the stepping responses that could potentially have a profound effect in reducing risk of falling. We describe the water-based balance training program and a study protocol to evaluate its efficacy (Trial registration number #NCT00708136. Methods/Design The proposed water-based training program involves use of unpredictable, multi-directional perturbations in a group setting to evoke compensatory and volitional stepping responses. Perturbations are made by pushing slightly the subjects and by water turbulence, in 24 training sessions conducted over 12 weeks. Concurrent cognitive tasks during movement tasks are included. Principles of physical training and exercise including awareness, continuity, motivation, overload, periodicity, progression and specificity were used in the development of this novel program. Specific goals are to increase the speed of stepping responses and improve the postural control mechanism and physical functioning. A prospective, randomized, cross-over trial with concealed allocation, assessor blinding and intention-to-treat analysis will be performed to evaluate the efficacy of the water-based training program. A total of 36 community-dwelling adults (age 65–88 with no recent history of instability or falling will be assigned to either the perturbation-based training or a control group (no training

  16. Closed metal supports

    Energy Technology Data Exchange (ETDEWEB)

    Dolotov, N P; Afanas' yev, Yu V; Brednev, V A; Nuzhadikhin, A G; Tsiplakov, B V; Uskov, I T

    1980-08-30

    A closed metal support system that has a specific profile includes roof timber, ledger and roof timber. For convenience of transport, assembly, disassembly and repeated use during operation of an extraction powered system, the uprights in the central part are made sectional and are connected to one another by a hinge for folding into transport position. Longitudinal openings are made at the ends of the uprights in order to provide strength by creating flexibility in the hinged connections. The hinged connections of the sectional uprights have elastic gaskets. For convenience in folding the reinforcement, the ends of the uprights of the roof timber and ledger have the shape of a channel at junctions of their hinged connection.

  17. Closed central slip injuries--a missed diagnosis?

    LENUS (Irish Health Repository)

    Nugent, N

    2011-09-01

    The extensor apparatus of the finger is a complex structure and injury can lead to significant digital dysfunction. Closed central slip injuries may be missed or diagnosis delayed because of lack of an open wound and often no radiographic abnormality, and can result in boutonniere deformities if untreated. This study aimed to quantify the number of patients attending with closed central slip injuries and to ascertain if the initial diagnosis was correct. The number of patients presenting to us over a 6 month period was recorded. The original diagnosis, time to diagnosis of central slip injury and the presence\\/absence of a boutonniere deformity were recorded. Ten patients were included in the study. Seven (70%) injuries were due to sport. Eight (80%) had a delayed diagnosis of central slip injury. Six (60%) had previously presented to general practitioners or emergency departments. Seven (70%) had boutonniere deformities. Closed central slip injuries can be missed. Simple clinical tests can diagnose central slip disruption.

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

    Science.gov (United States)

    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

  19. Current trends in the cardiovascular clinical trial arena (I

    Directory of Open Access Journals (Sweden)

    Pater Cornel

    2004-06-01

    Full Text Available Abstract The existence of effective therapies for most cardiovascular disease states, coupled with increased requirements that potential benefits of new drugs be evaluated on clinical rather than surrogate endpoints, makes it increasingly difficult to substantiate any incremental improvements in efficacy that these new drugs might offer. Compounding the problem is the highly controversial issue of comparing new agents with placebos rather than active pharmaceuticals in drug efficacy trials. Despite the recent consensus that placebos may be used ethically in well-defined, justifiable circumstances, the problem persists, in part because of increased scrutiny by ethics committees but also because of considerable lingering disagreement regarding the propriety and scientific value of placebo-controlled trials (and trials of antihypertensive drugs in particular. The disagreement also substantially affects the most viable alternative to placebo-controlled trials: actively controlled equivalence/noninferiority trials. To a great extent, this situation was prompted by numerous previous trials of this type that were marked by fundamental methodological flaws and consequent false claims, inconsistencies, and potential harm to patients. As the development and use of generic drugs continue to escalate, along with concurrent pressure to control medical costs by substituting less-expensive therapies for established ones, any claim that a new drug, intervention, or therapy is "equivalent" to another should not be accepted without close scrutiny. Adherence to proper methods in conducting studies of equivalence will help investigators to avoid false claims and inconsistencies. These matters will be addressed in the third article of this three-part series.

  20. Device for the simultaneous operation of the closing valve of a vessel and the closing valve of a transport container

    International Nuclear Information System (INIS)

    Tellier, Claude; Surriray, Michel.

    1982-01-01

    This device includes mechanisms for unlatching the closing valve of the vessel and securing it to the closing valve of the transport container and other mechanisms for vertically raising the assembly of valves, pivoting it and bringing it into a vertical position in a bulge provided in the bottom of the transport container. For example the first containment is a nuclear reactor vessel and the transport container is used for carrying an item from the vessel to an external area (for instance, a defective pump to the repair area) and for the return transport operation [fr

  1. New approaches to trials in glomerulonephritis.

    Science.gov (United States)

    Craig, Jonathan C; Tong, Allison; Strippoli, Giovanni F M

    2017-01-01

    Randomized controlled trials are required to reliably identify interventions to improve the outcomes for people with glomerulonephritis (GN). Unfortunately, although easier, observational studies are inherently unreliable even though the findings of both study designs agree most of the time. Currently there are ∼790 trials in GN, but suboptimal design and reporting, together with small sample sizes, mean that they may not be reliable for decision making. If the history is somewhat bleak, the future looks bright, with recent initiatives to improve the quality, size and relevance of clinical trials in nephrology, including greater patient engagement, trial networks, core outcome sets, registry-based trials and adaptive designs. Given the current state of the evidence informing the care of people with GN, disruptive technologies and pervasive culture change is required to ensure that the potential of trials to improve the health of people with this complex condition is to be realized. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  2. Implications of HIV PrEP Trials Results

    Science.gov (United States)

    Anton, Peter; Fletcher, Courtney V.; DeGruttola, Victor; McGowan, Ian; Becker, Stephen; Zwerski, Sheryl; Burns, David

    2011-01-01

    Abstract Six randomized clinical trials have been implemented to examine the efficacy of tenofovir disoproxil fumarate (TDF) and/or TDF/emtricitabine (TDF/FTC) as preexposure prophylaxis for HIV-1 infection (PrEP). Although largely complementary, the six trials have many similar features. As the earliest results become available, an urgent question may arise regarding whether changes should be made in the conduct of the other trials. To consider this in advance, a Consultation on the Implications of HIV Pre-Exposure Prophylaxis (PrEP) Trials Results sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation (BMGF) was held on January 29, 2010, at the Natcher Conference Center, NIH, Bethesda, MD. Participants included basic scientists, clinical researchers (including investigators performing the current PrEP trials), and representatives from the U.S. Food and Drug Administration (FDA) and the agencies sponsoring the trials: the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Agency for International Development (USAID), the BMGF, and the U.S. NIH. We report here a summary of the presentations and highlights of salient discussion topics from this workshop. PMID:20969483

  3. Pipe closing device

    International Nuclear Information System (INIS)

    Klahn, F.C.; Nolan, J.H.; Wills, C.

    1979-01-01

    The closing device closes the upper end of a support tube for monitoring samples. It meshes with the upper connecting piece of the monitorung sample capsule, and loads the capsule within the bore of the support tube, so that it is fixed but can be released. The closing device consists of an interlocking component with a chamber and several ratchets which hang down. The interlocking component surrounds the actuating component for positioning the ratchets. The interlocking and actuating components are movable axially relative to each other. (DG) [de

  4. Quantitative Quality Assurance in a Multicenter HARDI Clinical Trial at 3T

    Science.gov (United States)

    Zhou, Xiaopeng; Sakaie, Ken E.; Debbins, Josef P.; Kirsch, John E.; Tatsuoka, Curtis; Fox, Robert J.; Lowe, Mark J.

    2016-01-01

    A phantom-based quality assurance (QA) protocol was developed for a multicenter clinical trial including high angular resolution diffusion imaging (HARDI). A total of 27 3T MR scanners from 2 major manufacturers, GE (Discovery and Signa scanners) and Siemens (Trio and Skyra scanners), were included in this trial. With this protocol, agar phantoms doped to mimic relaxation properties of brain tissue are scanned on a monthly basis, and quantitative procedures are used to detect spiking and to evaluate eddy current and Nyquist ghosting artifacts. In this study, simulations were used to determine alarm thresholds for minimal acceptable signal-to-noise ratio (SNR). Our results showed that spiking artifact was the most frequently observed type of artifact. Overall, Trio scanners exhibited less eddy current distortion than GE scanners, which in turn showed less distortion than Skyra scanners. This difference was mainly caused by the different sequences used on these scanners. The SNR for phantom scans was closely correlated with the SNR from volunteers. Nearly all of the phantom measurements with artifact-free images were above the alarm threshold, suggesting that the scanners are stable longitudinally. Software upgrades and hardware replacement sometimes affected SNR substantially but sometimes did not. In light of these results, it is important to monitor longitudinal SNR with phantom QA to help interpret potential effects on in vivo measurements. Our phantom QA procedure for HARDI scans was successful in tracking scanner performance and detecting unwanted artifacts. PMID:27587227

  5. Closed-loop, open-source electrophysiology

    Directory of Open Access Journals (Sweden)

    John D Rolston

    2010-09-01

    Full Text Available Multiple extracellular microelectrodes (multi-electrode arrays, or MEAs effectively record rapidly varying neural signals, and can also be used for electrical stimulation. Multi-electrode recording can serve as artificial output (efferents from a neural system, while complex spatially and temporally targeted stimulation can serve as artificial input (afferents to the neuronal network. Multi-unit or local field potential recordings can not only be used to control real world artifacts, such as prostheses, computers or robots, but can also trigger or alter subsequent stimulation. Real-time feedback stimulation may serve to modulate or normalize aberrant neural activity, to induce plasticity, or to serve as artificial sensory input. Despite promising closed-loop applications, commercial electrophysiology systems do not yet take advantage of the bidirectional capabilities of multi-electrodes, especially for use in freely moving animals. We addressed this lack of tools for closing the loop with NeuroRighter, an open-source system including recording hardware, stimulation hardware, and control software with a graphical user interface. The integrated system is capable of multi-electrode recording and simultaneous patterned microstimulation triggered by recordings with minimal stimulation artifact. The potential applications of closed-loop systems as research tools and clinical treatments are broad; we provide one example where epileptic activity recorded by a multi-electrode probe is used to trigger targeted stimulation, via that probe, to freely moving rodents.

  6. Closing the patient-oncologist communication gap: a review of historic and current efforts.

    Science.gov (United States)

    Pham, A Khoa; Bauer, Marianne T; Balan, Stefan

    2014-03-01

    Effective communication is essential in developing any relationship--this is particularly true between oncologists and their patients. The patient-oncologist relationship is one of the most delicate in medicine, and given the strong emotions associated with cancer, successful communication plays a paramount role in the wellbeing of patients and oncologists. Significant advances to close the communication gap have occurred over the past several decades, largely by addressing deficiencies in the various stages of an oncologist's lengthy training: undergraduate medical education, residency and fellowship, and continuing medical education. Stemming from several milestones achieved by highly motivated groups of individuals, including the creation of consensus statements and guidelines by communication education experts, progress has been made to improve patient-oncologist communication. This progress is marked by the development of evidence-based communication skills training programs, such as Oncotalk and Comskil, in addition to the creation of distant-learning modalities, such as the Studying Communication in Oncologist-Patient Encounters trial. This review article outlines the history of communication education during medical education and training, and brings to light more recent efforts to promote competent, communication-minded physicians necessary for effective cancer care.

  7. Differences in reporting of analyses in internal company documents versus published trial reports: comparisons in industry-sponsored trials in off-label uses of gabapentin.

    Directory of Open Access Journals (Sweden)

    S Swaroop Vedula

    Full Text Available BACKGROUND: Details about the type of analysis (e.g., intent to treat [ITT] and definitions (i.e., criteria for including participants in the analysis are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported with descriptions in the corresponding internal company documents (i.e., what was planned and what was done. Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation. METHODS AND FINDINGS: For each trial, we compared internal company documents (protocols, statistical analysis plans, and research reports, all unpublished, with publications. One author extracted data and another verified, with a third person verifying discordant items and a sample of the rest. Extracted data included the number of participants randomized and analyzed for efficacy, and types of analyses for efficacy and safety and their definitions (i.e., criteria for including participants in each type of analysis. We identified 21 trials, 11 of which were published randomized controlled trials, and that provided the documents needed for planned comparisons. For three trials, there was disagreement on the number of randomized participants between the research report and publication. Seven types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including ITT and six others. The protocol or publication described ITT using six different definitions, resulting in frequent disagreements between the two documents (i.e., different numbers of participants were included in the analyses. CONCLUSIONS: Descriptions of analyses conducted did not agree between internal company documents and what was publicly reported. Internal company documents provide extensive documentation of methods planned and used, and trial

  8. Comparison of open and closed techniques of haemorrhoidectomy in terms of post-operative complications

    International Nuclear Information System (INIS)

    Majeed, S.; Qamar, S.R.; Tariq, M.; Ali, M.A.

    2015-01-01

    Haemorrhoids have been diagnosed and treated since the dawn of civilization, yet their cause, nature, symptomatology and especially their treatment options, remain hotly debated. The general principle however is that treatment should be directed by symptoms and the degree of haemorrhoids. The objective of the study is to compare early and late complications and wound healing time in open versus closed methods of haemorrhoidectomy. Methods: This was a Randomized control trial conducted at Department of Surgery CMH Kharian for a period of 3 years. During the period of study, patients presenting in Surgical OPD (Age Range 20-72 Years) with 3rd or 4th degree haemorrhoids requiring haemorrhoidectomy (n=364) were divided in two groups:- Group-1 was subjected to haemorrhoidectomy by open (Milligan-Morgan) technique and Group-2 underwent closed (Ferguson) haemorrhoidectomy. All patients were followed up for 2 months post-operatively and assessed for duration of wound healing and post-operative complications. Results: In group-1 (Open haemorrhoidectomy) patients ages ranged from 21-70 years with a mean age of 43 years (SD1±2.51). Duration of wound healing in this group was on the average 22 days (SD±5.76). Incidence of early post-operative complications including haemorrhage, infection and urinary retention was 4.94%, 8.24% and 7.14% respectively. The only late complication observed was anal stenosis in one patient (0.55%). No fissure or faecal incontinence was observed in this group. In group-2 (subjected to closed haemorrhoidectomy), patients ages ranged from 20-72 years with a mean age of 42 years (SD±10.31). Duration of wound healing was on the average 14 days (SD±3.25). Incidence of early post- operative complications, i.e., haemorrhage, infection and urinary retention was 2.19%, 7.69% and 2.75% respectively. No late complications (stenosis, fissure or incontinence) were observed in this group. Conclusion: There is no statistical significant difference between open

  9. Improving Clinical Trial Efficiency: Thinking outside the Box.

    Science.gov (United States)

    Mandrekar, Sumithra J; Dahlberg, Suzanne E; Simon, Richard

    2015-01-01

    Clinical trial design strategies have evolved over the past few years as a means to accelerate the drug development process so that the right therapies can be delivered to the right patients. Basket, umbrella, and adaptive enrichment strategies represent a class of novel designs for testing targeted therapeutics in oncology. Umbrella trials include a central infrastructure for screening and identification of patients, and focus on a single tumor type or histology with multiple subtrials, each testing a targeted therapy within a molecularly defined subset. Basket trial designs offer the possibility to include multiple molecularly defined subpopulations, often across histology or tumor types, but included in one cohesive design to evaluate the targeted therapy in question. Adaptive enrichment designs offer the potential to enrich for patients with a particular molecular feature that is predictive of benefit for the test treatment based on accumulating evidence from the trial. This review will aim to discuss the fundamentals of these design strategies, the underlying statistical framework, the logistical barriers of implementation, and, ultimately, the interpretation of the trial results. New statistical approaches, extensive multidisciplinary collaboration, and state of the art data capture technologies are needed to implement these strategies in practice. Logistical challenges to implementation arising from centralized assay testing, requirement of multiple specimens, multidisciplinary collaboration, and infrastructure requirements will also be discussed. This review will present these concepts in the context of the National Cancer Institute's precision medicine initiative trials: MATCH, ALCHEMIST, Lung MAP, as well as other trials such as FOCUS4.

  10. OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

    Science.gov (United States)

    Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

    2015-05-01

    The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  11. Simulation and correction of the closed orbit in the cooler synchrotron COSY

    International Nuclear Information System (INIS)

    Dinev, D.

    1990-11-01

    In this paper the problem of COSY closed orbit control and its correction is discussed. The results of a simulation of the COSY closed orbit and its correction using different correction methods are given. The interactive computer program ORBIT, created especially for the simulation and correction of the COSY closed orbit, is described. The paper includes as well a survey of the orbit correction methods and related topics. (orig.)

  12. Patient representatives' views on patient information in clinical cancer trials

    DEFF Research Database (Denmark)

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-01-01

    of future simplified and more attractive informed consent forms. CONCLUSIONS: The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language......BACKGROUND: Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed...... consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. METHODS: Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I...

  13. The DiaS trial

    DEFF Research Database (Denmark)

    Andreasson, Kate; Krogh, Jesper; Rosenbaum, Bent

    2014-01-01

    BACKGROUND: In Denmark 8,000 to 10,000 people will attempt suicide each year. The Centre of Excellence in Suicide Prevention in the Capital Region of Denmark is treating patients with suicidal behavior, and a recent survey has shown that 30% of the patients are suffering from borderline personali...... measured at week 28. Other exploratory outcomes are included such as severity of symptoms, suicide intention and ideation, depression, hopelessness, self-esteem, impulsivity, anger, and duration of respective treatments. TRIAL REGISTRATION: Clinical Trial.gov: NCT01512602....

  14. Potential efficiencies of open- and closed-cycle CO, supersonic, electric-discharge lasers

    Science.gov (United States)

    Monson, D. J.

    1976-01-01

    Computed open- and closed-cycle system efficiencies (laser power output divided by electrical power input) are presented for a CW carbon monoxide, supersonic, electric-discharge laser. Closed-system results include the compressor power required to overcome stagnation pressure losses due to supersonic heat addition and a supersonic diffuser. The paper shows the effect on the system efficiencies of varying several important parameters. These parameters include: gas mixture, gas temperature, gas total temperature, gas density, total discharge energy loading, discharge efficiency, saturated gain coefficient, optical cavity size and location with respect to the discharge, and supersonic diffuser efficiency. Maximum open-cycle efficiency of 80-90% is predicted; the best closed-cycle result is 60-70%.

  15. 34 CFR 685.214 - Closed school discharge.

    Science.gov (United States)

    2010-07-01

    ... the school's closing with any third party, such as the holder of a performance bond or a tuition... their successors, its sureties, and any private fund, including the portion of a public fund that represents funds received from a private party. (2) The provisions of this section apply notwithstanding any...

  16. Virtual grasping: closed-loop force control using electrotactile feedback.

    Science.gov (United States)

    Jorgovanovic, Nikola; Dosen, Strahinja; Djozic, Damir J; Krajoski, Goran; Farina, Dario

    2014-01-01

    Closing the control loop by providing somatosensory feedback to the user of a prosthesis is a well-known, long standing challenge in the field of prosthetics. Various approaches have been investigated for feedback restoration, ranging from direct neural stimulation to noninvasive sensory substitution methods. Although there are many studies presenting closed-loop systems, only a few of them objectively evaluated the closed-loop performance, mostly using vibrotactile stimulation. Importantly, the conclusions about the utility of the feedback were partly contradictory. The goal of the current study was to systematically investigate the capability of human subjects to control grasping force in closed loop using electrotactile feedback. We have developed a realistic experimental setup for virtual grasping, which operated in real time, included a set of real life objects, as well as a graphical and dynamical model of the prosthesis. We have used the setup to test 10 healthy, able bodied subjects to investigate the role of training, feedback and feedforward control, robustness of the closed loop, and the ability of the human subjects to generalize the control to previously "unseen" objects. Overall, the outcomes of this study are very optimistic with regard to the benefits of feedback and reveal various, practically relevant, aspects of closed-loop control.

  17. Virtual Grasping: Closed-Loop Force Control Using Electrotactile Feedback

    Directory of Open Access Journals (Sweden)

    Nikola Jorgovanovic

    2014-01-01

    Full Text Available Closing the control loop by providing somatosensory feedback to the user of a prosthesis is a well-known, long standing challenge in the field of prosthetics. Various approaches have been investigated for feedback restoration, ranging from direct neural stimulation to noninvasive sensory substitution methods. Although there are many studies presenting closed-loop systems, only a few of them objectively evaluated the closed-loop performance, mostly using vibrotactile stimulation. Importantly, the conclusions about the utility of the feedback were partly contradictory. The goal of the current study was to systematically investigate the capability of human subjects to control grasping force in closed loop using electrotactile feedback. We have developed a realistic experimental setup for virtual grasping, which operated in real time, included a set of real life objects, as well as a graphical and dynamical model of the prosthesis. We have used the setup to test 10 healthy, able bodied subjects to investigate the role of training, feedback and feedforward control, robustness of the closed loop, and the ability of the human subjects to generalize the control to previously “unseen” objects. Overall, the outcomes of this study are very optimistic with regard to the benefits of feedback and reveal various, practically relevant, aspects of closed-loop control.

  18. Slideline verification for multilayer pressure vessel and piping analysis including tangential motion

    International Nuclear Information System (INIS)

    Van Gulick, L.A.

    1984-01-01

    Nonlinear finite element method (FEM) computer codes with slideline algorithm implementations should be useful for the analysis of prestressed multilayer pressure vessels and piping. This paper presents closed form solutions including the effects of tangential motion useful for verifying slideline implementations for this purpose. The solutions describe stresses and displacements of a long internally pressurized elastic-plastic cylinder initially separated from an elastic outer cylinder by a uniform gap. Comparison of closed form and FEM results evaluates the usefulness of the closed form solution and the validity of the sideline implementation used

  19. Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

    Science.gov (United States)

    Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

    2017-12-01

    The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

  20. An experimental study on crib fires in a closed compartment

    Directory of Open Access Journals (Sweden)

    Dhurandher Bhisham Kumar

    2017-01-01

    Full Text Available An experimental investigation on burning behavior of fire in closed compartments is presented. Fire experiments were performed in a closed compartment of interior dimensions 4 × 4 × 4 m (length × width × height with ply board cribs as fire source. The parameters including the gas temperature, mass loss rate, heat flux, flame temperature, and compartment pressure were measured during the experiments. Experimental results indicated that the providing sudden ventilation to the closed compartment had great influence on the behavior of fire. The mass loss rate of the burning crib increased by 150% due to sudden ventilation which results in the increase in heat release rate by 198 kW. From the perspective of total heat flux, compartment pressure, and gas temperatures closed compartment with sudden ventilation were more hazardous.

  1. The OA Trial Bank

    DEFF Research Database (Denmark)

    van Middelkoop, Marienke; Arden, N K; Atchia, I.

    2016-01-01

    Objective: To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials. Design: Randomized trials evaluating one or more IA...... glucocorticoid preparation in patients with knee or hip OA, published from 1995 up to June 2012 were selected from the literature. IPD obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks...... Interval 1.50-26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points. Conclusions: This IPD meta...

  2. Quality of clinical trials: A moving target

    Science.gov (United States)

    Bhatt, Arun

    2011-01-01

    Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

  3. The CYTONOX trial

    DEFF Research Database (Denmark)

    Gade, Christina; Mikus, Gerd; Christensen, Hanne Rolighed

    2016-01-01

    INTRODUCTION: In Denmark, it is estimated that 3-5% of children are obese. Obesity is associated with pathophysiological alterations that may lead to alterations in the pharmacokinetics of drugs. In adults, obesity was found to influence important drug-metabolising enzyme pathways. The impact...... of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults. An altered drug metabolism may contribute significantly to therapeutic failure or toxicity. The aim of this trial is to investigate the in vivo activity of CYP3A4, CYP2E......1 and CYP1A2 substrates in obese versus non-obese children. METHODS: The CYTONOX trial is an open-label explorative pharmacokinetic trial. We intend to include 50 obese and 50 non-obese children. The primary end points are: in vivo clearance of CYP3A4, CYP2E1 and CYP1A2 substrates, which...

  4. School Closings in Philadelphia

    Science.gov (United States)

    Jack, James; Sludden, John

    2013-01-01

    In 2012, the School District of Philadelphia closed six schools. In 2013, it closed 24. The closure of 30 schools has occurred amid a financial crisis, headlined by the district's $1.35 billion deficit. School closures are one piece of the district's plan to cut expenditures and close its budget gap. The closures are also intended to make…

  5. Single-trial effective brain connectivity patterns enhance discriminability of mental imagery tasks

    Science.gov (United States)

    Rathee, Dheeraj; Cecotti, Hubert; Prasad, Girijesh

    2017-10-01

    Objective. The majority of the current approaches of connectivity based brain-computer interface (BCI) systems focus on distinguishing between different motor imagery (MI) tasks. Brain regions associated with MI are anatomically close to each other, hence these BCI systems suffer from low performances. Our objective is to introduce single-trial connectivity feature based BCI system for cognition imagery (CI) based tasks wherein the associated brain regions are located relatively far away as compared to those for MI. Approach. We implemented time-domain partial Granger causality (PGC) for the estimation of the connectivity features in a BCI setting. The proposed hypothesis has been verified with two publically available datasets involving MI and CI tasks. Main results. The results support the conclusion that connectivity based features can provide a better performance than a classical signal processing framework based on bandpass features coupled with spatial filtering for CI tasks, including word generation, subtraction, and spatial navigation. These results show for the first time that connectivity features can provide a reliable performance for imagery-based BCI system. Significance. We show that single-trial connectivity features for mixed imagery tasks (i.e. combination of CI and MI) can outperform the features obtained by current state-of-the-art method and hence can be successfully applied for BCI applications.

  6. Map of open and closed chromatin domains in Drosophila genome.

    Science.gov (United States)

    Milon, Beatrice; Sun, Yezhou; Chang, Weizhong; Creasy, Todd; Mahurkar, Anup; Shetty, Amol; Nurminsky, Dmitry; Nurminskaya, Maria

    2014-11-18

    Chromatin compactness has been considered a major determinant of gene activity and has been associated with specific chromatin modifications in studies on a few individual genetic loci. At the same time, genome-wide patterns of open and closed chromatin have been understudied, and are at present largely predicted from chromatin modification and gene expression data. However the universal applicability of such predictions is not self-evident, and requires experimental verification. We developed and implemented a high-throughput analysis for general chromatin sensitivity to DNase I which provides a comprehensive epigenomic assessment in a single assay. Contiguous domains of open and closed chromatin were identified by computational analysis of the data, and correlated to other genome annotations including predicted chromatin "states", individual chromatin modifications, nuclear lamina interactions, and gene expression. While showing that the widely trusted predictions of chromatin structure are correct in the majority of cases, we detected diverse "exceptions" from the conventional rules. We found a profound paucity of chromatin modifications in a major fraction of closed chromatin, and identified a number of loci where chromatin configuration is opposite to that expected from modification and gene expression patterns. Further, we observed that chromatin of large introns tends to be closed even when the genes are expressed, and that a significant proportion of active genes including their promoters are located in closed chromatin. These findings reveal limitations of the existing predictive models, indicate novel mechanisms of epigenetic regulation, and provide important insights into genome organization and function.

  7. Recruitment strategies and challenges in a large intervention trial: Systolic Blood Pressure Intervention Trial (SPRINT)

    Science.gov (United States)

    Ramsey, Thomas M; Snyder, Joni K; Lovato, Laura C; Roumie, Christianne L; Glasser, Steven P; Cosgrove, Nora M; Olney, Christine M; Tang, Rocky H; Johnson, Karen C; Still, Carolyn H; Gren, Lisa H; Childs, Jeffery C; Crago, Osa L; Summerson, John H; Walsh, Sandy M; Perdue, Letitia H; Bankowski, Denise M; Goff, David C

    2016-01-01

    Background The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter, randomized clinical trial of 9,361 participants with hypertension who are ≥ 50 years old. The trial is designed to evaluate the effect of intensive systolic blood pressure control (systolic blood pressure goal recruitment strategies and lessons learned during recruitment of the SPRINT cohort and five targeted participant subgroups: pre-existing cardiovascular disease, pre-existing chronic kidney disease, age ≥ 75 years, women, and minorities. Methods In collaboration with the National Institutes of Health Project Office and SPRINT Coordinating Center, five Clinical Center Networks oversaw clinical site selection, recruitment, and trial activities. Recruitment began November 8, 2010 and ended March 15, 2013 (about 28 months). Various recruitment strategies were used, including mass mailing, brochures, referrals from healthcare providers or friends, posters, newspaper ads, radio ads, and electronic medical record searches. Results Recruitment was scheduled to last 24 months to enroll a target of 9,250 participants; in just over 28 months, the trial enrolled 9,361 participants. The trial screened 14,692 volunteers, with 33% of initial screens originating from the use of mass mailing lists. Screening results show that participants also responded to recruitment efforts through referral by SPRINT staff, healthcare providers, or friends (45%); brochures or posters placed in clinic waiting areas (15%); and television, radio, newspaper, internet ads, or toll-free numbers (8%). The overall recruitment yield (number randomized /number screened) was 64% (9,361 randomized /14,692 screened), 77% for those with cardiovascular disease, 79% for those with chronic kidney disease, 70% for those age ≥ 75 years, 55% for women, and 61% for minorities. As recruitment was observed to lag behind expectations, additional clinics were included and inclusion criteria were broadened, keeping event rates

  8. Update on the third international stroke trial (IST-3 of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

    Directory of Open Access Journals (Sweden)

    Sandercock Peter

    2011-11-01

    Full Text Available Abstract Background Intravenous recombinant tissue plasminogen activator (rtPA is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. Design International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. Results The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2% of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. Conclusion The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and

  9. Impact of sending email reminders of the legal requirement for posting results on ClinicalTrials.gov: cohort embedded pragmatic randomized controlled trial.

    Science.gov (United States)

    Maruani, Annabel; Boutron, Isabelle; Baron, Gabriel; Ravaud, Philippe

    2014-09-19

    To evaluate the impact of sending an email to responsible parties of completed trials that do not comply with the Food and Drug Administration Amendments Act 801 legislation, to remind them of the legal requirement to post results. Cohort embedded pragmatic randomized controlled trial. Trials registered on ClinicalTrials.gov. 190 out of 379 trials randomly selected by computer generated randomization list to receive the intervention (personalized emails structured as a survey and sent by one of us to responsible parties of the trials, indirectly reminding them of the legal requirement and potential penalties for non-compliance). The primary outcome was the proportion of results posted on ClinicalTrials.gov at three months. The secondary outcome was the proportion posted at six months. In a second step, two assessors blinded to the intervention group collected the date of the first results being received on ClinicalTrials.gov. A post hoc sensitivity analysis excluding trials wrongly included was performed. Among 379 trials included, 190 were randomized to receive the email intervention. The rate of posting of results did not differ at three months between trials with or without the intervention: 36/190 (19%) v 24/189 (13%), respectively (relative risk 1.5, 95% confidence interval 0.9 to 2.4, P=0.096) but did at six months: 46/190 (24%) v 27/189 (14%), 1.7, 1.1 to 2.6, P=0.014. In the sensitivity analysis, which excluded 48/379 trials (13%), 26/190 (14%) and 22/189 (12%), respectively, results were significant at three months (relative risk 5.1, 1.1 to 22.9, P=0.02) and at six months (4.1, 1.3 to 10.6, P=0.001). Sending email reminders about the FDA's legal requirement to post results at ClinicalTrials.gov improved significantly the posting rate at six months but not at three months.Trial registration ClinicalTrials.gov NCT01658254. © Maruani et al 2014.

  10. Clinical Trials

    Medline Plus

    Full Text Available ... Trial Protocol Each clinical trial has a master plan called a protocol (PRO-to-kol). This plan explains how the trial will work. The trial ... clinical trial; and detailed information about the treatment plan. Eligibility Criteria A clinical trial's protocol describes what ...

  11. Methods for determining enzymatic activity comprising heating and agitation of closed volumes

    Science.gov (United States)

    Thompson, David Neil; Henriksen, Emily DeCrescenzo; Reed, David William; Jensen, Jill Renee

    2016-03-15

    Methods for determining thermophilic enzymatic activity include heating a substrate solution in a plurality of closed volumes to a predetermined reaction temperature. Without opening the closed volumes, at least one enzyme is added, substantially simultaneously, to the closed volumes. At the predetermined reaction temperature, the closed volumes are agitated and then the activity of the at least one enzyme is determined. The methods are conducive for characterizing enzymes of high-temperature reactions, with insoluble substrates, with substrates and enzymes that do not readily intermix, and with low volumes of substrate and enzyme. Systems for characterizing the enzymes are also disclosed.

  12. Closed Loop Experiment Manager (CLEM—An Open and Inexpensive Solution for Multichannel Electrophysiological Recordings and Closed Loop Experiments

    Directory of Open Access Journals (Sweden)

    Hananel Hazan

    2017-10-01

    Full Text Available There is growing need for multichannel electrophysiological systems that record from and interact with neuronal systems in near real-time. Such systems are needed, for example, for closed loop, multichannel electrophysiological/optogenetic experimentation in vivo and in a variety of other neuronal preparations, or for developing and testing neuro-prosthetic devices, to name a few. Furthermore, there is a need for such systems to be inexpensive, reliable, user friendly, easy to set-up, open and expandable, and possess long life cycles in face of rapidly changing computing environments. Finally, they should provide powerful, yet reasonably easy to implement facilities for developing closed-loop protocols for interacting with neuronal systems. Here, we survey commercial and open source systems that address these needs to varying degrees. We then present our own solution, which we refer to as Closed Loop Experiments Manager (CLEM. CLEM is an open source, soft real-time, Microsoft Windows desktop application that is based on a single generic personal computer (PC and an inexpensive, general-purpose data acquisition board. CLEM provides a fully functional, user-friendly graphical interface, possesses facilities for recording, presenting and logging electrophysiological data from up to 64 analog channels, and facilities for controlling external devices, such as stimulators, through digital and analog interfaces. Importantly, it includes facilities for running closed-loop protocols written in any programming language that can generate dynamic link libraries (DLLs. We describe the application, its architecture and facilities. We then demonstrate, using networks of cortical neurons growing on multielectrode arrays (MEA that despite its reliance on generic hardware, its performance is appropriate for flexible, closed-loop experimentation at the neuronal network level.

  13. Issues in data monitoring and interim analysis of trials.

    Science.gov (United States)

    Grant, A M; Altman, D G; Babiker, A B; Campbell, M K; Clemens, F J; Darbyshire, J H; Elbourne, D R; McLeer, S K; Parmar, M K B; Pocock, S J; Spiegelhalter, D J; Sydes, M R; Walker, A E; Wallace, S A

    2005-03-01

    To address issues about data monitoring committees (DMCs) for randomised controlled trials (RCTs). Electronic databases. Handsearching of selected books. Personal contacts with experts in the field. Systematic literature reviews of DMCs and small group processes in decision-making; sample surveys of: reports of RCTs, recently completed and ongoing RCTs and policies of major organisations involved in RCTs; case studies of four DMCs; and interviews with experienced DMC members. All focused on 23 prestated questions. Although still a minority, RCTs increasingly have DMCs. There is wide agreement that nearly all trials need some form of data monitoring. Central to the role of the DMC is monitoring accumulating evidence related to benefit and toxicity; variation in emphasis has been reflected in the plethora of names. DMCs for trials performed for regulatory purposes should be aware of any special requirements and regulatory consequences. Advantages were identified for both larger and smaller DMCs. There is general agreement that a DMC should be independent and multidisciplinary. Consumer and ethicist membership is controversial. The chair is recognised as being particularly influential, and likely to be most effective if he or she is experienced, understands both statistical and clinical issues, and is facilitating in style and impartial. There is no evidence available to judge suggested approaches to training. The review suggested that costs should be covered, but other rewards must be so minimal as to not affect decision-making. It is usual to have a minimum frequency of DMC meetings, with evidence that face-to-face meetings are preferable. It is common to have open sessions and a closed session. A report to a DMC should cover benefits and risks in a balanced way, summarised in an accessible style, avoiding excessive detail, and be as current as possible. Disadvantages of blinded analyses seem to outweigh advantages. Information about comparable studies should be

  14. Distributed Autonomous Control of Multiple Spacecraft During Close Proximity Operations

    National Research Council Canada - National Science Library

    McCamish, Shawn B

    2007-01-01

    This research contributes to multiple spacecraft control by developing an autonomous distributed control algorithm for close proximity operations of multiple spacecraft systems, including rendezvous...

  15. Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

    Science.gov (United States)

    Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

    2014-07-16

    To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

  16. A proposal for an effective interacting field theory of open and closed strings

    International Nuclear Information System (INIS)

    Baulieu, L.; Grossman, B.

    1987-01-01

    We propose the use of the reggeon-pomeron vertex to obtain an effective field theory for open and closed strings. We suggest that closed string fields are necessary in order to go off-shell in an open string field theory. We then find that the closed string fields satisfy the Virasoro constraints (including equal number of left and right movers) in an appropriate choice of gauge. (orig.)

  17. No short-cut in assessing trial quality: a case study

    Directory of Open Access Journals (Sweden)

    Hirji Karim F

    2009-01-01

    Full Text Available Abstract Background Assessing the quality of included trials is a central part of a systematic review. Many check-list type of instruments for doing this exist. Using a trial of antibiotic treatment for acute otitis media, Burke et al., BMJ, 1991, as the case study, this paper illustrates some limitations of the check-list approach to trial quality assessment. Results The general verdict from the check list type evaluations in nine relevant systematic reviews was that Burke et al. (1991 is a good quality trial. All relevant meta-analyses extensively used its data to formulate therapeutic evidence. My comprehensive evaluation, on the other hand, brought to the surface a series of serious problems in the design, conduct, analysis and report of this trial that were missed by the earlier evaluations. Conclusion A check-list or instrument based approach, if used as a short-cut, may at times rate deeply flawed trials as good quality trials. Check lists are crucial but they need to be augmented with an in-depth review, and where possible, a scrutiny of the protocol, trial records, and original data. The extent and severity of the problems I uncovered for this particular trial warrant an independent audit before it is included in a systematic review.

  18. Protocol for a scoping review of post-trial extensions of randomised controlled trials using individually linked administrative and registry data.

    Science.gov (United States)

    Fitzpatrick, Tiffany; Perrier, Laure; Tricco, Andrea C; Straus, Sharon E; Jüni, Peter; Zwarenstein, Merrick; Lix, Lisa M; Smith, Mark; Rosella, Laura C; Henry, David A

    2017-02-17

    Well-conducted randomised controlled trials (RCTs) provide the least biased estimates of intervention effects. However, RCTs are costly and time-consuming to perform and long-term follow-up of participants may be hampered by lost contacts and financial constraints. Advances in computing and population-based registries have created new possibilities for increasing the value of RCTs by post-trial extension using linkage to routinely collected administrative/registry data in order to determine long-term interventional effects. There have been recent important examples, including 20+ years follow-up studies of trials of pravastatin and mammography. Despite the potential value of post-trial extension, there has been no systematic study of this literature. This scoping review aims to characterise published post-trial extension studies, assess their value, and identify any potential challenges associated with this approach. This review will use the recommended methods for scoping reviews. We will search MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A draft search strategy is included in this protocol. Review of titles and abstracts, full texts of potentially eligible studies and data/information extraction will be conducted independently by pairs of investigators. Eligible studies will be RCTs that investigated healthcare interventions that were extended by individual linkage to administrative/registry/electronic medical records data after the completion of the planned follow-up period. Information concerning the original trial, characteristics of the extension study, any clinical, policy or ethical implications and methodological or practical challenges will be collected using standardised forms. As this study uses secondary data, and does not include person-level data, ethics approval is not required. We aim to disseminate these findings through journals and conferences targeting triallists and researchers involved in health data linkage. We

  19. Transparency and public accessibility of clinical trial information in Croatia: how it affects patient participation in clinical trials.

    Science.gov (United States)

    Šolić, Ivana; Stipčić, Ana; Pavličević, Ivančica; Marušić, Ana

    2017-06-15

    Despite increased visibility of clinical trials through international trial registries, patients often remain uninformed of their existence, especially if they do not have access to adequate information about clinical research, including the language of the information. The aim of this study was to describe the context for transparency of clinical trials in Croatia in relation to countries in Central and Eastern Europe, and to assess how informed Croatian patients are about clinical trials and their accessibility. We assessed the transparency of clinical trials from the data available in the public domain. We also conducted an anonymous survey on a convenience sample of 257 patients visiting two family medicine offices or an oncology department in south Croatia, and members of national patients' associations. Despite legal provisions for transparency of clinical trials in Croatia, they are still not sufficiently visible in the public domain. Among countries from Central and Eastern Europe, Croatia has the fewest number of registered trials in the EU Clinical Trials Registry. 66% of the patients in the survey were aware of the existence of clinical trials but only 15% were informed about possibilities of participating in a trial. Although 58% of the respondents were willing to try new treatments, only 6% actually participated in a clinical trial. Only 2% of the respondents were aware of publicly available trial registries. Our study demonstrates that there is low transparency of clinical trials in Croatia, and that Croatian patients are not fully aware of clinical trials and the possibilities of participating in them, despite reported availability of Internet resources and good communication with their physicians. There is a need for active policy measures to increase the awareness of and access to clinical trials to patients in Croatia, particularly in their own language.

  20. Advancing the educational and career pathway for clinical trials nurses.

    Science.gov (United States)

    Scott, Kathleen; White, Kathryn; Roydhouse, Jessica K

    2013-04-01

    Clinical trials nurses play a pivotal role in the conduct of clinical research, but the educational and career pathway for these nurses remains unclear. This article reports findings from a survey of nurses working in cancer clinical trials research in Australia. Most participants held postgraduate qualifications (42 of 61); however, clinical trials education was primarily attained through short professional development courses. Interest in pursuing trial-specific postgraduate education was high, but barriers were identified, including cost, time, and unclear benefit for career advancement. Job titles varied substantially, which is indicative of an unclear employment pathway. These findings suggest that initiatives to improve the educational and career pathway for clinical trials nurses are needed and should include the following: formal educational preparation, greater consistency in employment status, and clearer career progression. These strategies should be underpinned by broad professional recognition of the clinical trials nurse as a specialized nursing role. Copyright 2013, SLACK Incorporated.

  1. Diagnostic conversion to bipolar disorder in unipolar depressed patients participating in trials on antidepressants.

    Science.gov (United States)

    Holmskov, J; Licht, R W; Andersen, K; Bjerregaard Stage, T; Mørkeberg Nilsson, F; Bjerregaard Stage, K; Valentin, J B; Bech, P; Ernst Nielsen, R

    2017-02-01

    In unipolar depressed patients participating in trials on antidepressants, we investigated if illness characteristics at baseline could predict conversion to bipolar disorder. A long-term register-based follow-up study of 290 unipolar depressed patients with a mean age of 50.8 years (SD=11.9) participating in three randomized trials on antidepressants conducted in the period 1985-1994. The independent effects of explanatory variables were examined by applying Cox regression analyses. The overall risk of conversion was 20.7%, with a mean follow-up time of 15.2 years per patient. The risk of conversion was associated with an increasing number of previous depressive episodes at baseline, [HR 1.18, 95% CI (1.10-1.26)]. No association with gender, age, age at first depressive episode, duration of baseline episode, subtype of depression or any of the investigated HAM-D subscales included was found. The patients were followed-up through the Danish Psychiatric Central Research Register, which resulted in inherent limitations such as possible misclassification of outcome. In a sample of middle-aged hospitalized unipolar depressed patients participating in trials on antidepressants, the risk of conversion was associated with the number of previous depressive episodes. Therefore, this study emphasizes that unipolar depressed patients experiencing a relatively high number of recurrences should be followed more closely, or at least be informed about the possible increased risk of conversion. Copyright © 2016. Published by Elsevier Masson SAS.

  2. Preparations for the next generation of clinical trials with proton therapy

    International Nuclear Information System (INIS)

    Newhauser, W.D.; Smith, A.R.; Fitzek, M.; Ibbott, G.; Munzenrider, J.

    2002-01-01

    Full text: As proton radiation therapy centers become more widely available, we anticipate an increase in clinical proton therapy research, e.g. clinical trials to compare the efficacy of proton therapy with that of conformal photon therapy. In this presentation, we explore some of the quality assurance (QA) work that will be necessary to support multi-institution clinical trials to include facilities in Europe, Asia and the United States. Specifically, we shall concentrate on three areas pertaining to practical clinical proton dosimetry for which clear, concise, and coherent guidance is needed. First, the existing proton therapy dosimetry protocols (e.g. ICRU Report 59, IAEA TRS-398) provide general methods that are well suited for adoption in proton therapy. Many additional techniques are required in order to implement dosimetry in a contemporary proton clinic. For example, special situations arise for small fields including those for radiosurgery and ocular treatments, and for rotational therapy. Fortunately, this additional information is emerging from various proton therapy centers. For example, Vatnitsky et al. described the dosimetry of small beams, Newhauser et al. described absolute proton dosimetry techniques for radiosurgery and for ocular beams. Newhauser et al. also reported on a general formalism and practical methods for dosimetry measurements in a rotational proton gantry. Our aim is to discuss some specific needs for the standardization of these tasks, which will be essential in achieving adequate uniformity in multi-institution clinical trials. Second, we will discuss means to standardize of writing the physics QA portion of protocols for multi-institution clinical trials, through which a statistically significant number of patient outcomes may be obtained more rapidly. Surprisingly, only two multi-institution proton clinical trials have been undertaken (a skull base sarcoma trial and a prostate cancer trial, both shared between MGH and Loma Linda

  3. 75 FR 7370 - Closed Captioning of Video Programming; Closed Captioning Requirements for Digital Television...

    Science.gov (United States)

    2010-02-19

    ... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 79 [CG Docket No. 05-231; ET Docket No. 99-254; FCC 08-255] Closed Captioning of Video Programming; Closed Captioning Requirements for Digital Television... Captioning of Video Programming; Closed Captioning Requirements for Digital Television Receivers, Declaratory...

  4. A Randomized trial of an Asthma Internet Self-management Intervention (RAISIN): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Morrison, Deborah; Wyke, Sally; Thomson, Neil C; McConnachie, Alex; Agur, Karolina; Saunderson, Kathryn; Chaudhuri, Rekha; Mair, Frances S

    2014-05-24

    The financial costs associated with asthma care continue to increase while care remains suboptimal. Promoting optimal self-management, including the use of asthma action plans, along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally. Despite evidence of benefit, guided self-management remains underused, however the potential for online resources to promote self-management behaviors is gaining increasing recognition. The aim of this paper is to describe the protocol for a pilot evaluation of a website 'Living well with asthma' which has been developed with the aim of promoting self-management behaviors shown to improve outcomes. The study is a parallel randomized controlled trial, where adults with asthma are randomly assigned to either access to the website for 12 weeks, or usual asthma care for 12 weeks (followed by access to the website if desired). Individuals are included if they are over 16-years-old, have a diagnosis of asthma with an Asthma Control Questionnaire (ACQ) score of greater than, or equal to 1, and have access to the internet. Primary outcomes for this evaluation include recruitment and retention rates, changes at 12 weeks from baseline for both ACQ and Asthma Quality of Life Questionnaire (AQLQ) scores, and quantitative data describing website usage (number of times logged on, length of time logged on, number of times individual pages looked at, and for how long). Secondary outcomes include clinical outcomes (medication use, health services use, lung function) and patient reported outcomes (including adherence, patient activation measures, and health status). Piloting of complex interventions is considered best practice and will maximise the potential of any future large-scale randomized controlled trial to successfully recruit and be able to report on necessary outcomes. Here we will provide results across a range of outcomes which will provide estimates of

  5. Clinical Trials

    Medline Plus

    Full Text Available ... Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, or ... humans. What Are Clinical Trials? Clinical trials are research studies that explore whether a medical strategy, treatment, or ...

  6. Quality of radiotherapy reporting in randomized controlled trials of prostate cancer.

    Science.gov (United States)

    Soon, Yu Yang; Chen, Desiree; Tan, Teng Hwee; Tey, Jeremy

    2018-06-07

    Good radiotherapy reporting in clinical trials of prostate radiotherapy is important because it will allow accurate reproducibility of radiotherapy treatment and minimize treatment variations that can affect patient outcomes. The aim of our study is to assess the quality of prostate radiotherapy (RT) treatment reporting in randomized controlled trials in prostate cancer. We searched MEDLINE for randomized trials of prostate cancer, published from 1996 to 2016 and included prostate RT as one of the intervention arms. We assessed if the investigators reported the ten criteria adequately in the trial reports: RT dose prescription method; RT dose-planning procedures; organs at risk (OAR) dose constraints; target volume definition, simulation procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance (QA) as well as presence or absence of deviations in RT treatment planning and delivery. We performed multivariate logistic regression to determine the factors that may influence the quality of reporting. We found 59 eligible trials. There was significant variability in the quality of reporting. Target volume definition, total RT dose and fractionation schedule were reported adequately in 97% of included trials. OAR constraints, simulation procedures and presence or absence of deviations in RT treatment planning and delivery were reported adequately in 30% of included trials. Twenty-four trials (40%) reported seven criteria or more adequately. Multivariable logistic analysis showed that trials that published their quality assurance results and cooperative group trials were more likely to have adequate quality in reporting in at least seven criteria. There is significant variability in the quality of reporting on prostate radiotherapy treatment in randomized trials of prostate cancer. We need to have consensus guidelines to standardize the reporting of radiotherapy treatment in randomized trials.

  7. Solid oxide fuel cell field trial evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Wilcox, C.P.; Winstanley, R.; Nietsch, T.; Smith, C.; Knight, R.; Seymore, C.

    2000-07-01

    This report focuses on issues relating to a field trial of a solid oxide fuel cell (SOFC). Aspects examined include markets for SOFC systems, the choice of systems for demonstration in year 2002, the assessment of industrial interest, and evaluation and ranking of candidate systems. The identification and evaluation of interest in field trials, the estimation of the capital and running costs of a field trial, and identification of the benefits to the UK and barriers to implementation of SOFC systems are discussed. (UK)

  8. Research design considerations for single-dose analgesic clinical trials in acute pain

    DEFF Research Database (Denmark)

    Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C

    2016-01-01

    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...

  9. Quality of clinical trials: A moving target

    Directory of Open Access Journals (Sweden)

    Arun Bhatt

    2011-01-01

    Full Text Available Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials.

  10. Dose Escalation Methods in Phase I Cancer Clinical Trials

    OpenAIRE

    Le Tourneau, Christophe; Lee, J. Jack; Siu, Lillian L.

    2009-01-01

    Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-...

  11. Study of the trial subjects’ protection aspects in Phase I clinical trials and bioequivalence studies

    Directory of Open Access Journals (Sweden)

    K. O. Zupanets

    2016-03-01

    Full Text Available Protection of rights, health and well-being of persons who are taking the drug during the trial (trial subjects is one of the basic principles of clinical trials (CT management. Aim. In order to study key aspects of volunteer protection, determine factors that influence these indicators and estimate the importance of ensuring their proper implementation on the clinical site (CS three survey of 135 trial subjects were carried out to evaluate the importance of assessing the impact of factors such as the procedure of signing the informed consent (IC at the CS and testing procedures for HIV / AIDS, hepatitis and others. Assessment of the quality of life of trial subjects as indirect indicator of the quality of clinical trials that ensures the proper protection of their life was the subject of the third survey. Methods and results. The general model of the relationship between the key aspects of the trial subjects protection and the factors which are providing them during the clinical trials of drugs management was substantiated, which included the main aspects of the trial subjects’ protection, protective factors and basic CT management procedures, the impact of the above factors on the possibility of providing protection aspects depends on their implementation quality. It was found that trial subjects’ protection improvement can be achieved during the IC signing process. It is necessary to ensure a higher level of volunteers understanding of the terms that could be used in the IC form. Regarding the procedure of compulsory testing for HIV/AIDS in the course of screening, we can conclude that the majority of the trial subjects believe that this procedure is an additional factor in their health protection and do not consider it as an excessive psychological pressure on them. Conclusion. Assessing the quality of life during the bioequivalence study at the CS makes possible to reach a conclusion on general well-being and satisfaction with those

  12. Influences on visit retention in clinical trials: insights from qualitative research during the VOICE trial in Johannesburg, South Africa.

    Science.gov (United States)

    Magazi, Busisiwe; Stadler, Jonathan; Delany-Moretlwe, Sinead; Montgomery, Elizabeth; Mathebula, Florence; Hartmann, Miriam; van der Straten, Ariane

    2014-07-28

    Although significant progress has been made in clinical trials of women-controlled methods of HIV prevention such as microbicides and Pre-exposure Prophylaxis (PrEP), low adherence to experimental study products remains a major obstacle to being able to establish their efficacy in preventing HIV infection. One factor that influences adherence is the ability of trial participants to attend regular clinic visits at which trial products are dispensed, adherence counseling is administered, and participant safety is monitored. We conducted a qualitative study of the social contextual factors that influenced adherence in the VOICE (MTN-003) trial in Johannesburg, South Africa, focusing on study participation in general, and study visits in particular. The research used qualitative methodologies, including in-depth interviews (IDI), serial ethnographic interviews (EI), and focus group discussions (FGD) among a random sub-sample of 102 female trial participants, 18 to 40 years of age. A socio-ecological framework that explored those factors that shaped trial participation and adherence to study products, guided the analysis. Key codes were developed to standardize subsequent coding and a node search was used to identify texts relating to obstacles to visit adherence. Our analysis includes coded transcripts from seven FGD (N = 40), 41 IDI, and 64 serial EI (N = 21 women). Women's kinship, social, and economic roles shaped their ability to participate in the clinical trial. Although participants expressed strong commitments to attend study visits, clinic visit schedules and lengthy waiting times interfered with their multiple obligations as care givers, wage earners, housekeepers, and students. The research findings highlight the importance of the social context in shaping participation in HIV prevention trials, beyond focusing solely on individual characteristics. This points to the need to focus interventions to improve visit attendance by promoting a culture of

  13. DLR-EnviHab - A closed environmental Habitat

    Science.gov (United States)

    Rabbow, E.; Koch, B.; Rettberg, P.; Horneck, G.; Graef, P.; Gerzer, R.

    Closed habitats intended for different purposes like confinement studies, life in extreme environments (Antarctica) and as simulation testbeds for complex closed life support systems have been built and achieved different degrees of closure. Those that were built in preparation of space missions oriented themselves on the need of a crew of astronauts during a long term mission in Space, on Mars or Moon. At DLR in Cologne, a modular approach is followed to build a closed environmental habitat for scientific and medical studies, the DLR-EnviHab. This modular structure of the EnviHab is designed to include humans as integral part in a bioregenerative life support system, and allows a step-wise realization of the project, ensuring useful results for a wide field of scientific research during each phase. The DLR-EnviHab provides a platform for international and interdisciplinary research and the development of innovative solutions for cultivation and habitation on Earth as well as for long term space or planetary missions. By the inclusion of humans as integral component of the system, medical research areas including physiological and psychological health and rehabilitation as well as environmental research and monitoring and modelling of coupled and controlled systems are addressed in EnviHab. Results of the research conducted in the individual and combined EnviHab modules will also contribute to most urgent issues like water(recycling) management, food management, pollution/waste management and atmosphere(air) management. In addition, EnviHab contributes to public education and outreach with the open visible and partly accessible structure, an exhibition and an explanatory module.

  14. 12 CFR 225.131 - Activities closely related to banking.

    Science.gov (United States)

    2010-01-01

    ...; operation and management of a trust department; international banking; foreign exchange transactions... specialized lending provisions; marketing operations, including research, market development and advertising... Holding Companies Interpretations § 225.131 Activities closely related to banking. (a) Bank management...

  15. Closed and Open Loop Subspace System Identification of the Kalman Filter

    Directory of Open Access Journals (Sweden)

    David Di Ruscio

    2009-04-01

    Full Text Available Some methods for consistent closed loop subspace system identification presented in the literature are analyzed and compared to a recently published subspace algorithm for both open as well as for closed loop data, the DSR_e algorithm. Some new variants of this algorithm are presented and discussed. Simulation experiments are included in order to illustrate if the algorithms are variance efficient or not.

  16. Sensitivity analysis for missing dichotomous outcome data in multi-visit randomized clinical trial with randomization-based covariance adjustment.

    Science.gov (United States)

    Li, Siying; Koch, Gary G; Preisser, John S; Lam, Diana; Sanchez-Kam, Matilde

    2017-01-01

    Dichotomous endpoints in clinical trials have only two possible outcomes, either directly or via categorization of an ordinal or continuous observation. It is common to have missing data for one or more visits during a multi-visit study. This paper presents a closed form method for sensitivity analysis of a randomized multi-visit clinical trial that possibly has missing not at random (MNAR) dichotomous data. Counts of missing data are redistributed to the favorable and unfavorable outcomes mathematically to address possibly informative missing data. Adjusted proportion estimates and their closed form covariance matrix estimates are provided. Treatment comparisons over time are addressed with Mantel-Haenszel adjustment for a stratification factor and/or randomization-based adjustment for baseline covariables. The application of such sensitivity analyses is illustrated with an example. An appendix outlines an extension of the methodology to ordinal endpoints.

  17. Personal oral hygiene and dental caries: A systematic review of randomised controlled trials.

    Science.gov (United States)

    Hujoel, Philippe Pierre; Hujoel, Margaux Louise A; Kotsakis, Georgios A

    2018-05-15

    To conduct a systematic review of randomised trials assessing the association between personal oral hygiene and dental caries in the absence of the confounding effects of fluoride. Dental caries continues to affect close to 100% of the global population. There is a century-old conflict on whether dental caries is caused by poor oral hygiene or poorly formed teeth (ie, teeth with dental defects). Resolving this conflict is of significant public health importance as these two hypotheses on dental caries aetiology can lead to different prevention strategies. A systematic search for randomised trials was conducted using predefined criteria in 3 databases. The impact of personal oral hygiene interventions on coronal dental caries incidence was evaluated using random-effects models. Three randomised studies involving a total of 743 participants were included. Personal oral hygiene interventions failed to influence the incidence of dental caries (Δ Decayed, Missing and Filled Surfaces (DFMS) = -0.11; 95% confidence interval: (-0.91, 0.69; P-value Personal oral hygiene in the absence of fluorides has failed to show a benefit in terms of reducing the incidence of dental caries. © 2018 The Authors. Gerodontology published by British Society of Gerodontology, European College of Gerodontology and Geriatric Oral Research Group and John Wiley & Sons Ltd.

  18. OARSI Clinical Trials Recommendations

    DEFF Research Database (Denmark)

    Katz, J N; Losina, E; Lohmander, L S

    2015-01-01

    To highlight methodological challenges in the design and conduct of randomized trials of surgical interventions and to propose strategies for addressing these challenges. This paper focuses on three broad areas: enrollment; intervention; and assessment including implications for analysis. For eac...

  19. Assessing the readability of ClinicalTrials.gov.

    Science.gov (United States)

    Wu, Danny T Y; Hanauer, David A; Mei, Qiaozhu; Clark, Patricia M; An, Lawrence C; Proulx, Joshua; Zeng, Qing T; Vydiswaran, V G Vinod; Collins-Thompson, Kevyn; Zheng, Kai

    2016-03-01

    ClinicalTrials.gov serves critical functions of disseminating trial information to the public and helping the trials recruit participants. This study assessed the readability of trial descriptions at ClinicalTrials.gov using multiple quantitative measures. The analysis included all 165,988 trials registered at ClinicalTrials.gov as of April 30, 2014. To obtain benchmarks, the authors also analyzed 2 other medical corpora: (1) all 955 Health Topics articles from MedlinePlus and (2) a random sample of 100,000 clinician notes retrieved from an electronic health records system intended for conveying internal communication among medical professionals. The authors characterized each of the corpora using 4 surface metrics, and then applied 5 different scoring algorithms to assess their readability. The authors hypothesized that clinician notes would be most difficult to read, followed by trial descriptions and MedlinePlus Health Topics articles. Trial descriptions have the longest average sentence length (26.1 words) across all corpora; 65% of their words used are not covered by a basic medical English dictionary. In comparison, average sentence length of MedlinePlus Health Topics articles is 61% shorter, vocabulary size is 95% smaller, and dictionary coverage is 46% higher. All 5 scoring algorithms consistently rated CliniclTrials.gov trial descriptions the most difficult corpus to read, even harder than clinician notes. On average, it requires 18 years of education to properly understand these trial descriptions according to the results generated by the readability assessment algorithms. Trial descriptions at CliniclTrials.gov are extremely difficult to read. Significant work is warranted to improve their readability in order to achieve CliniclTrials.gov's goal of facilitating information dissemination and subject recruitment. Published by Oxford University Press on behalf of the American Medical Informatics Association 2015. This work is written by US Government

  20. Function impairment and pain after closed treatment of fractures of the mandibular condyle

    NARCIS (Netherlands)

    Dijkstra, P.U.; Stegenga, B.; de Bont, L.G.; Bos, R.R.

    Background: To determine the prognosis of fractures of the mandibular condyle after closed treatment. Methods: Patients (n = 144) with a fracture of the mandibular condyle, all treated closed, were included in the study. Fracture types and position of the fracture parts were determined on

  1. Adhesive strip wound closure after thyroidectomy/parathyroidectomy: a prospective, randomized controlled trial.

    LENUS (Irish Health Repository)

    O'Leary, D Peter

    2013-03-01

    Conventional collar incision closure in thyroid and parathyroid surgery involves the insertion of an epidermal layer of subcutaneous absorbable sutures that are reinforced by a deep layer of sutures. Adhesive strips offer an alternative method to close the epidermal layer. The aim of this study was to compare adhesive strip closure with absorbable sutures for collar incisions in a prospective, single-blinded, randomized controlled trial.

  2. Mitochondrial disease patient motivations and barriers to participate in clinical trials.

    Directory of Open Access Journals (Sweden)

    Zarazuela Zolkipli-Cunningham

    Full Text Available Clinical treatment trials are increasingly being designed in primary mitochondrial disease (PMD, a phenotypically and genetically heterogeneous collection of inherited multi- system energy deficiency disorders that lack effective therapy. We sought to identify motivating factors and barriers to clinical trial participation in PMD.A survey study was conducted in two independent mitochondrial disease subject cohorts. A discovery cohort invited subjects with well-defined biochemical or molecularly- confirmed PMD followed at a single medical center (CHOP, n = 30/67 (45% respondents. A replication cohort included self-identified PMD subjects in the Rare Disease Clinical Research Network (RDCRN national contact registry (n = 290/1119 (26% respondents. Five-point Likert scale responses were analyzed using descriptive and quantitative statistics. Experienced and prioritized symptoms for trial participation, and patient attitudes toward detailed aspects of clinical trial drug features and study design.PMD subjects experienced an average of 16 symptoms. Muscle weakness, chronic fatigue, and exercise intolerance were the lead symptoms encouraging trial participation. Motivating trial design factors included a self-administered study drug; vitamin, antioxidant, natural or plant-derivative; pills; daily treatment; guaranteed treatment access during and after study; short travel distances; and late-stage (phase 3 participation. Relative trial participation barriers included a new study drug; discontinuation of current medications; disease progression; daily phlebotomy; and requiring participant payment. Treatment trial type or design preferences were not influenced by population age (pediatric versus adult, prior research trial experience, or disease severity.These data are the first to convey clear PMD subject preferences and priorities to enable improved clinical treatment trial design that cuts across the complex diversity of disease. Partnering with rare

  3. Low luminance/eyes closed and monochromatic stimulations reduce variability of flash visual evoked potential latency

    Directory of Open Access Journals (Sweden)

    Senthil Kumar Subramanian

    2013-01-01

    Full Text Available Context: Visual evoked potentials are useful in investigating the physiology and pathophysiology of the human visual system. Flash visual evoked potential (FVEP, though technically easier, has less clinical utility because it shows great variations in both latency and amplitude for normal subjects. Aim: To study the effect of eye closure, low luminance, and monochromatic stimulation on the variability of FVEPs. Subjects and Methods: Subjects in self-reported good health in the age group of 18-30 years were divided into three groups. All participants underwent FVEP recording with eyes open and with white light at 0.6 J luminance (standard technique. Next recording was done in group 1 with closed eyes, group 2 with 1.2 and 20 J luminance, and group 3 with red and blue lights, while keeping all the other parameters constant. Two trials were given for each eye, for each technique. The same procedure was repeated at the same clock time on the following day. Statistical Analysis: Variation in FVEP latencies between the individuals (interindividual variability and the variations within the same individual for four trials (intraindividual variability were assessed using coefficient of variance (COV. The technique with lower COV was considered the better method. Results: Recording done with closed eyes, 0.6 J luminance, and monochromatic light (blue > red showed lower interindividual and intraindividual variability in P2 and N2 as compared to standard techniques. Conclusions: Low luminance flash stimulations and monochromatic light will reduce FVEP latency variability and may be clinically useful modifications of FVEP recording technique.

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

    Science.gov (United States)

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

    2014-01-01

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

  5. Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC): study protocol for a randomised, stepped-wedge cluster trial within the EFFECTS trial.

    Science.gov (United States)

    Lundström, Erik; Isaksson, Eva; Wester, Per; Laska, Ann-Charlotte; Näsman, Per

    2018-01-08

    Many randomised controlled trials (RCTs) fail to meet their recruitment goals in time. Trialists are advised to include study recruitment strategies within their trials. EFFECTS is a Swedish, academic-led RCT of fluoxetine for stroke recovery. The trial's primary objective is to investigate whether 20 mg fluoxetine daily compared with placebo for 6 months after an acute stroke improves the patient's functional outcome. The first patient was included on 20 October 2014 and, as of 31 August 2017, EFFECTS has included 810 of planned 1500 individuals. EFFECTS currently has 32 active centres. The primary objective of the ERUTECC (Enhancing Recruitment Using Teleconference and Commitment Contract) study is to investigate whether a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% at 60 days post intervention, compared with 60 days pre-intervention, in an ongoing RCT. ERUTECC is a randomised, stepped-wedge cluster trial embedded in EFFECTS. The plan is to start ERUTECC with a running-in period of September 2017. The first intervention is due in October 2017, and the study will continue for 12 months. We are planning to intervene at all active centres in EFFECTS, except the five top recruiting centres (n = 27). The rationale for not intervening at the top recruiting centres is that we believe they have reached their full potential and the intervention would be too weak for them. The hypothesis of this study is that a structured teleconference re-visit with the study personnel at the centres, accompanied by a commitment contract, can enhance recruitment by 20% 60 days post intervention, compared to 60 days pre-intervention, in an ongoing RCT. EFFECTS is a large, pragmatic RCT of stroke in Sweden. Results from the embedded ERUTECC study could probably be generalised to high-income Western countries, and is relevant to trial management and could improve trial management in the

  6. Progressive Derechos in the Presence of Closed Upper-level Subtropical Anticyclones

    Science.gov (United States)

    Guastini, C.; Bosart, L. F.

    2013-12-01

    Progressive derechos are a type of long-lived mesoscale convective system that produces large swaths of wind damage. In contrast to their serial derecho counterparts, which form in association with extratropical cyclones, progressive derechos often occur in the presence of benign synoptic conditions on the poleward side of closed upper-level subtropical anticyclones. Forecasters have been known to struggle predicting progressive derechos with any certainty due to the common lack of large-scale support for severe weather in regimes dominated by anticyclonic conditions. This study will classify a group of days on which there was a closed upper-level anticyclone over the United States and a progressive derecho did not occur and a group of days on which there was a closed upper-level anticyclone over the United States and a progressive derecho did occur, examine the synoptic environments of the two groups, and identify derecho null cases. By analyzing the null cases, derecho failure modes will be determined, which will help forecaster situational awareness and reveal the science behind the environmental conditions necessary for, and detrimental to, derecho development. This presentation will include climatologies of both derechos and closed upper-level anticyclones over the United States for June, July, and August of the years 1994-2013 (the modern radar era). The presentation will also include closed anticyclone-relative composites of both derecho cases and derecho null cases. The composites will elucidate which conditions are necessary for, and which are detrimental to, derecho development. The hypothesis is that derecho failure days occur due either to the lack of a triggering mechanism or other phenomena working against convective development such as a strong capping inversion or transverse ageostrophic circulations around an upper-level jet creating subsidence in an otherwise favorable environment. A representative case study will be included to highlight a common

  7. Decision aids for people considering taking part in clinical trials.

    Science.gov (United States)

    Gillies, Katie; Cotton, Seonaidh C; Brehaut, Jamie C; Politi, Mary C; Skea, Zoe

    2015-11-27

    Several interventions have been developed to promote informed consent for participants in clinical trials. However, many of these interventions focus on the content and structure of information (e.g. enhanced information or changes to the presentation format) rather than the process of decision making. Patient decision aids support a decision making process about medical options. Decision aids support the decision process by providing information about available options and their associated outcomes, alongside information that enables patients to consider what value they place on particular outcomes, and provide structured guidance on steps of decision making. They have been shown to be effective for treatment and screening decisions but evidence on their effectiveness in the context of informed consent for clinical trials has not been synthesised. To assess the effectiveness of decision aids for clinical trial informed consent compared to no intervention, standard information (i.e. usual practice) or an alternative intervention on the decision making process. We searched the following databases and to March 2015: Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library; MEDLINE (OvidSP) (from 1950); EMBASE (OvidSP) (from 1980); PsycINFO (OvidSP) (from 1806); ASSIA (ProQuest) (from 1987); WHO International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch/); ClinicalTrials.gov; ISRCTN Register (http://www.controlled-trials.com/isrctn/). We also searched reference lists of included studies and relevant reviews. We contacted study authors and other experts. There were no language restrictions. We included randomised and quasi-randomised controlled trials comparing decision aids in the informed consent process for clinical trials alone, or in conjunction with standard information (such as written or verbal) or alongside alternative interventions (e.g. paper-based versus web-based decision aids). Included trials involved

  8. Nonlinear Stochastic Models for Water Level Dynamics in Closed Lakes

    OpenAIRE

    Mishchenko, A.S.; Zelikin, M.I.; Zelikina, L.F.

    1995-01-01

    This paper presents the results of investigation of nonlinear mathematical models of the behavior of closed lakes using the example of the Caspian Sea. Forecasting the level of the Caspian Sea is crucial both for the economy of the region and for the region's environment. The Caspian Sea is a closed reservoir; it is well known that its level changes considerably due to a variety of factors including global climate change. A series of forecasts exists based on different methods and taking...

  9. Can Cardiovascular Epidemiology and Clinical Trials Close the Risk Management Gap Between Diabetes and Prediabetes?

    DEFF Research Database (Denmark)

    Perreault, Leigh; Færch, Kristine; Gregg, Edward W

    2017-01-01

    PURPOSE OF REVIEW: We reviewed published literature to determine the relationship between A1c and cardiovascular disease (CVD) and summarize the need and implications for CVD risk reduction with interventions, focusing in the prediabetic A1c range (... a continuous relationship between A1c and CVD-even below the current levels of A1c-defined prediabetes and after adjustment for known risk factors for CVD. Clinical trials have demonstrated a reduction in CV morbidity and/or mortality when interventions are invoked in the prediabetic A1c range. Guidelines...... advocating CV risk factor management in prediabetes have not been widely adopted, subsequently leading to comparable coronary heart disease risk between people with prediabetes (HR = 1.9, 95% CI 1.7-2.1 vs normoglycemia) and diabetes itself (HR=2.0, 95% CI 1.8-2.2 vs no diabetes). This review highlights...

  10. Landscape of early clinical trials for childhood and adolescence cancer in Spain.

    Science.gov (United States)

    Bautista, F; Gallego, S; Cañete, A; Mora, J; Diaz de Heredia, C; Cruz, O; Fernández, J M; Rives, S; Madero, L; Castel, V; Cela, M E; Ramírez, G; Sábado, C; Acha, T; Astigarraga, I; Sastre, A; Muñoz, A; Guibelalde, M; Moreno, L

    2016-07-01

    Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.

  11. Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

    Science.gov (United States)

    Cummings, J; Aisen, P; Barton, R; Bork, J; Doody, R; Dwyer, J; Egan, J C; Feldman, H; Lappin, D; Truyen, L; Salloway, S; Sperling, R; Vradenburg, G

    2016-06-01

    Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

  12. Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Pedersen, Court; Law, Matthew

    2002-01-01

    OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA...

  13. Feasibility, Process, and Outcomes of Cardiovascular Clinical Trial Data Sharing: A Reproduction Analysis of the SMART-AF Trial.

    Science.gov (United States)

    Gay, Hawkins C; Baldridge, Abigail S; Huffman, Mark D

    2017-12-01

    Data sharing is as an expanding initiative for enhancing trust in the clinical research enterprise. To evaluate the feasibility, process, and outcomes of a reproduction analysis of the THERMOCOOL SMARTTOUCH Catheter for the Treatment of Symptomatic Paroxysmal Atrial Fibrillation (SMART-AF) trial using shared clinical trial data. A reproduction analysis of the SMART-AF trial was performed using the data sets, data dictionary, case report file, and statistical analysis plan from the original trial accessed through the Yale Open Data Access Project using the SAS Clinical Trials Data Transparency platform. SMART-AF was a multicenter, single-arm trial evaluating the effectiveness and safety of an irrigated, contact force-sensing catheter for ablation of drug refractory, symptomatic paroxysmal atrial fibrillation in 172 participants recruited from 21 sites between June 2011 and December 2011. Analysis of the data was conducted between December 2016 and April 2017. Effectiveness outcomes included freedom from atrial arrhythmias after ablation and proportion of participants without any arrhythmia recurrence over the 12 months of follow-up after a 3-month blanking period. Safety outcomes included major adverse device- or procedure-related events. The SMART AF trial participants' mean age was 58.7 (10.8) years, and 72% were men. The time from initial proposal submission to final analysis was 11 months. Freedom from atrial arrhythmias at 12 months postprocedure was similar compared with the primary study report (74.0%; 95% CI, 66.0-82.0 vs 76.4%; 95% CI, 68.7-84.1). The reproduction analysis success rate was higher than the primary study report (65.8%; 95% CI 56.5-74.2 vs 75.6%; 95% CI, 67.2-82.5). Adverse events were minimal and similar between the 2 analyses, but contact force range or regression models could not be reproduced. The feasibility of a reproduction analysis of the SMART-AF trial was demonstrated through an academic data-sharing platform. Data sharing can be

  14. Closed cycle electric discharge laser design investigation

    Science.gov (United States)

    Baily, P. K.; Smith, R. C.

    1978-01-01

    Closed cycle CO2 and CO electric discharge lasers were studied. An analytical investigation assessed scale-up parameters and design features for CO2, closed cycle, continuous wave, unstable resonator, electric discharge lasing systems operating in space and airborne environments. A space based CO system was also examined. The program objectives were the conceptual designs of six CO2 systems and one CO system. Three airborne CO2 designs, with one, five, and ten megawatt outputs, were produced. These designs were based upon five minute run times. Three space based CO2 designs, with the same output levels, were also produced, but based upon one year run times. In addition, a conceptual design for a one megawatt space based CO laser system was also produced. These designs include the flow loop, compressor, and heat exchanger, as well as the laser cavity itself. The designs resulted in a laser loop weight for the space based five megawatt system that is within the space shuttle capacity. For the one megawatt systems, the estimated weight of the entire system including laser loop, solar power generator, and heat radiator is less than the shuttle capacity.

  15. Memory as social glue: Close interpersonal relationships in amnesic patients

    Directory of Open Access Journals (Sweden)

    Patrick S.R. Davidson

    2012-12-01

    Full Text Available Memory may be crucial for establishing and/or maintaining social bonds. Using the National Social life, Health, and Aging Project questionnaire, we examined close interpersonal relationships in three amnesic people: K.C. and D.A. (who are adult-onset cases and H.C. (who has developmental amnesia. All three patients were less involved than demographically-matched controls with neighbors and religious and community groups. A higher-than-normal percentage of the adult-onset (K.C. and D.A. cases’ close relationships were with family members, and they had made few new close friends in the decades since the onset of their amnesia. On the other hand, the patient with developmental amnesia (H.C. had forged a couple of close relationships, including one with her fiancé. Social networks appear to be winnowed, but not obliterated, by amnesia. The obvious explanation for the patients’ reduced social functioning stems from their memory impairment, but we discuss other potentially important factors for future study.

  16. Biopharmaceutical industry-sponsored global clinical trials in emerging countries.

    Science.gov (United States)

    Alvarenga, Lenio Souza; Martins, Elisabeth Nogueira

    2010-01-01

    To evaluate biopharmaceutical industry-sponsored clinical trials placed in countries previously described as emerging regions for clinical research, and potential differences for those placed in Brazil. Data regarding recruitment of subjects for clinical trials were retrieved from www.clinicaltrials.gov on February 2nd 2009. Proportions of sites in each country were compared among emerging countries. Multiple logistic regressions were performed to evaluate whether trial placement in Brazil could be predicted by trial location in other countries and/or by trial features. A total of 8,501 trials were then active and 1,170 (13.8%) included sites in emerging countries (i.e., Argentina, Brazil, China, Czech Republic, Hungary, India, Mexico, Poland, Russia, South Korea, and South Africa). South Korea and China presented a significantly higher proportion of sites when compared to other countries (pattractiveness for biopharmaceutical industry-sponsored clinical trials.

  17. Closed and open breathing circuit function in healthy volunteers during exercise at Mount Everest base camp (5300 m).

    LENUS (Irish Health Repository)

    McMorrow, R C N

    2012-08-01

    We present a randomised, controlled, crossover trial of the Caudwell Xtreme Everest (CXE) closed circuit breathing system vs an open circuit and ambient air control in six healthy, hypoxic volunteers at rest and exercise at Everest Base Camp, at 5300 m. Compared with control, arterial oxygen saturations were improved at rest with both circuits. There was no difference in the magnitude of this improvement as both circuits restored median (IQR [range]) saturation from 75%, (69.5-78.9 [68-80]%) to > 99.8% (p = 0.028). During exercise, the CXE closed circuit improved median (IQR [range]) saturation from a baseline of 70.8% (63.8-74.5 [57-76]%) to 98.8% (96.5-100 [95-100]%) vs the open circuit improvement to 87.5%, (84.1-88.6 [82-89]%; p = 0.028). These data demonstrate the inverse relationship between supply and demand with open circuits and suggest that ambulatory closed circuits may offer twin advantages of supplying higher inspired oxygen concentrations and\\/or economy of gas use for exercising hypoxic adults.

  18. Assessing Cognitive Function in Bipolar Disorder: Challenges and Recommendations for Clinical Trial Design

    Science.gov (United States)

    Burdick, Katherine E.; Ketter, Terence A.; Goldberg, Joseph F.; Calabrese, Joseph R.

    2015-01-01

    OBJECTIVE Neurocognitive impairment in schizophrenia has been recognized for more than a century. In contrast, only recently have significant neurocognitive deficits been recognized in bipolar disorder. Converging data suggest the importance of cognitive problems in relation to quality of life in bipolar disorder, highlighting the need for treatment and prevention efforts targeting cognition in bipolar patients. Future treatment trials targeting cognitive deficits will be met with methodological challenges due to the inherent complexity and heterogeneity of the disorder, including significant diagnostic comorbidities, the episodic nature of the illness, frequent use of polypharmacy, cognitive heterogeneity, and a lack of consensus regarding measurement of cognition and outcome in bipolar patients. Guidelines for use in designing future trials are needed. PARTICIPANTS The members of the consensus panel (each of the bylined authors) were selected based upon their expertise in bipolar disorder. Dr. Burdick is a neuropsychologist who has studied cognition in this illness for 15 years; Drs. Ketter, Calabrese, and Goldberg each bring considerable expertise in the treatment of bipolar disorder both within and outside of controlled clinical trials. This consensus statement was derived from work together at scientific meetings (e.g. symposium presention at the 2014 Annual meeting of the American Society of Clinical Psychopharmacology, among others) and ongoing discussions by conference call. With the exception of the public presentations on this topic, these meetings were closed to outside participants. EVIDENCE A literature review was undertaken by the authors to identify illness-specific challenges relevant to the design and conduct of treatment trials targeting neurocognition in bipolar disorder. Expert opinion from each of the authors guided the consensus recommendations. CONSENSUS PROCESS Consensus recommendations, reached by unanimous opinion of the authors, are

  19. Training in Innovative Technologies for Close-Range Sensing in Alpine Terrain

    Science.gov (United States)

    Rutzinger, M.; Bremer, M.; Höfle, B.; Hämmerle, M.; Lindenbergh, R.; Oude Elberink, S.; Pirotti, F.; Scaioni, M.; Wujanz, D.; Zieher, T.

    2018-05-01

    The 2nd international summer school "Close-range sensing techniques in Alpine terrain" was held in July 2017 in Obergurgl, Austria. Participants were trained in selected close-range sensing methods, such as photogrammetry, laser scanning and thermography. The program included keynotes, lectures and hands-on assignments combining field project planning, data acquisition, processing, quality assessment and interpretation. Close-range sensing was applied for different research questions of environmental monitoring in high mountain environments, such as geomorphologic process quantification, natural hazard management and vegetation mapping. The participants completed an online questionnaire evaluating the summer school, its content and organisation, which helps to improve future summer schools.

  20. 27 CFR 44.146 - Closing.

    Science.gov (United States)

    2010-04-01

    ... PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Operations by Export Warehouse Proprietors Inventories § 44.146 Closing. A closing inventory shall be made by the export warehouse proprietor when he transfers ownership or concludes business. Where the proprietor transfers ownership the closing inventory shall be made...

  1. Clinical Trials

    Medline Plus

    Full Text Available ... take part in a clinical trial. When researchers think that a trial's potential risks are greater than ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find ...

  2. Clinical Trials

    Medline Plus

    Full Text Available ... to-kol). This plan explains how the trial will work. The trial is led by a principal ... for the clinical trial. The protocol outlines what will be done during the clinical trial and why. ...

  3. Clinical Trials

    Medline Plus

    Full Text Available ... questions and clinical trials. Optimizing our Clinical Trials Enterprise NHLBI has a strong tradition of supporting clinical ... multi-pronged approach to Optimize our Clinical Trials Enterprise that will make our clinical trials enterprise even ...

  4. Clinical Trials

    Medline Plus

    Full Text Available ... of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are ... earlier than they would be in general medical practice. This is because late-phase trials have large ...

  5. Clinical Trials

    Medline Plus

    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...

  6. Clinical Trials

    Medline Plus

    Full Text Available ... clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a ... will be done during the clinical trial and why. Each medical center that does the study uses ...

  7. Analysis of Smart Composite Structures Including Debonding

    Science.gov (United States)

    Chattopadhyay, Aditi; Seeley, Charles E.

    1997-01-01

    Smart composite structures with distributed sensors and actuators have the capability to actively respond to a changing environment while offering significant weight savings and additional passive controllability through ply tailoring. Piezoelectric sensing and actuation of composite laminates is the most promising concept due to the static and dynamic control capabilities. Essential to the implementation of these smart composites are the development of accurate and efficient modeling techniques and experimental validation. This research addresses each of these important topics. A refined higher order theory is developed to model composite structures with surface bonded or embedded piezoelectric transducers. These transducers are used as both sensors and actuators for closed loop control. The theory accurately captures the transverse shear deformation through the thickness of the smart composite laminate while satisfying stress free boundary conditions on the free surfaces. The theory is extended to include the effect of debonding at the actuator-laminate interface. The developed analytical model is implemented using the finite element method utilizing an induced strain approach for computational efficiency. This allows general laminate geometries and boundary conditions to be analyzed. The state space control equations are developed to allow flexibility in the design of the control system. Circuit concepts are also discussed. Static and dynamic results of smart composite structures, obtained using the higher order theory, are correlated with available analytical data. Comparisons, including debonded laminates, are also made with a general purpose finite element code and available experimental data. Overall, very good agreement is observed. Convergence of the finite element implementation of the higher order theory is shown with exact solutions. Additional results demonstrate the utility of the developed theory to study piezoelectric actuation of composite

  8. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.

    Science.gov (United States)

    Hemmingsen, Bianca; Christensen, Louise Lundby; Wetterslev, Jørn; Vaag, Allan; Gluud, Christian; Lund, Søren S; Almdal, Thomas

    2012-04-19

    To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes. Systematic review of randomised clinical trials with meta-analyses and trial sequential analyses. The Cochrane Library, Medline, Embase, Science Citation Index Expanded, Latin American Caribbean Health Sciences Literature, and Cumulative Index to Nursing and Allied Health Literature until March 2011. We also searched abstracts presented at the American Diabetes Association and European Association for the Study of Diabetes Congresses, contacted relevant trial authors and pharmaceutical companies, hand searched reference lists of included trials, and searched the US Food and Drug Administration website. Two authors independently screened titles and abstracts for randomised clinical trials comparing metformin and insulin versus insulin alone (with or without placebo) in patients with type 2 diabetes, older than 18 years, and with an intervention period of at least 12 weeks. We included trials irrespective of language, publication status, predefined outcomes, antidiabetic interventions used before randomisation, and reported outcomes. We included 26 randomised trials with 2286 participants, of which 23 trials with 2117 participants could provide data. All trials had high risk of bias. Data were sparse for outcomes relevant to patients. Metformin and insulin versus insulin alone did not significantly affect all cause mortality (relative risk 1.30, 95% confidence interval 0.57 to 2.99) or cardiovascular mortality (1.70, 0.35 to 8.30). Trial sequential analyses showed that more trials were needed before reliable conclusions could be drawn regarding these outcomes. In a fixed effect model, but not in a random effects model, severe hypoglycaemia was significantly more frequent with metformin and insulin than with insulin alone (2.83, 1.17 to 6.86). In a random effects model, metformin and insulin resulted in reduced Hb

  9. A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial.

    Science.gov (United States)

    Langhorne, Peter; Wu, Olivia; Rodgers, Helen; Ashburn, Ann; Bernhardt, Julie

    2017-09-01

    Mobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit. We assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke. We conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation. The trial took place in 56 acute stroke units in five countries. We included adult patients with a first or recurrent stroke who met physiological inclusion criteria. Patients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke. The primary outcome was good recovery [modified Rankin scale (mRS) score of 0-2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose-response analysis. Patients, outcome assessors and investigators involved in the trial were blinded to treatment allocation. We recruited 2104 (UK, n  = 610; Australasia, n  = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours; p  pattern of an improved odds of efficacy and safety outcomes in association with increased daily frequency of out-of-bed sessions but a reduced odds with an increased amount of mobilisation (minutes per day). UC clinicians started mobilisation earlier each year altering the context of the trial. Other potential confounding factors included staff patient interaction. Patients in the VEM group were mobilised earlier and with a higher dose of therapy than those in the UC group, which was already early. This VEM protocol was associated with reduced odds of favourable

  10. 27 CFR 40.426 - Closing.

    Science.gov (United States)

    2010-04-01

    ... TOBACCO Manufacture of Cigarette Papers and Tubes Operations by Manufacturers § 40.426 Closing. A closing report, covering the period from the first of the month to the date of the closing inventory, shall be made with such inventory. (72 Stat. 1422; 26 U.S.C. 5722) Inventories ...

  11. Trial protocol OPPTIMUM– Does progesterone prophylaxis for the prevention of preterm labour improve outcome?

    Directory of Open Access Journals (Sweden)

    Norman Jane E

    2012-08-01

    Full Text Available Abstract Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth. Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks, improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome. Trial

  12. Risk factors for avascular necrosis after closed reduction for developmental dysplasia of the hip.

    Science.gov (United States)

    Schur, Mathew D; Lee, Christopher; Arkader, Alexandre; Catalano, Anthony; Choi, Paul D

    2016-06-01

    The purpose of this study was to identify and evaluate risk factors of avascular necrosis (AVN) after closed treatment for developmental dysplasia of the hip (DDH). A retrospective review of children diagnosed with DDH at a tertiary-care children's hospital between 1986 and 2009 was performed. The presence of AVN was assessed according to Salter's classification system. Eighty-two affected hips in 70 children with an average age of 10 months at closed reduction (range 1-31 months) and 5 years (range 2-19 years) of follow-up met the inclusion criteria. Twenty-nine (of 82, 35 %) affected hips developed AVN. The use of pre-reduction traction (p = 0.019) increased the risk of AVN, while preoperative Pavlik harness or brace trial (p = 0.28), presence of ossific nucleus at the time of closed reduction (p = 0.16), and adductor tenotomy (p = 0.37) were not significant factors. Laterality (right vs. left) was also not a significant risk factor (p = 0.75), but patients who underwent closed reduction for bilateral DDH were less likely to develop AVN (p = 0.027). Overall, the degree of abduction did not affect the rate of AVN (p = 0.87). However, in patients treated with closed reduction younger than 6 months of age, the rate of AVN was increased with abduction ≥50° (9/15, 60 %) compared to abduction AVN were more likely to require subsequent surgery (p = 0.034) and more likely to report a fair/poor clinical outcome (p = 0.049). The risk of AVN (35 %) following closed reduction and spica casting for DDH is high. The degree of abduction in spica casts appears to be a risk factor in patients ≤6 months old. The authors recommend that abduction in spica casts should be limited to <50° in children younger than 6 months of age. IV.

  13. 7 CFR 1927.56 - Scheduling loan closing.

    Science.gov (United States)

    2010-01-01

    ... REGULATIONS TITLE CLEARANCE AND LOAN CLOSING Real Estate Title Clearance and Loan Closing § 1927.56 Scheduling loan closing. The agency, in coordination with the closing agent, will arrange a loan closing and send loan closing instructions, on an agency form to the closing agent when the agency determines that the...

  14. 7 CFR 1735.94 - Final approval and closing procedure.

    Science.gov (United States)

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE GENERAL POLICIES, TYPES OF LOANS, LOAN REQUIREMENTS-TELECOMMUNICATIONS PROGRAM Requirements for All Acquisitions and Mergers § 1735.94 Final approval and closing procedure. (a) Legal documents relating to the acquisition or merger, including copies of required franchises, commission orders...

  15. Production planning and control of closed-loop supply chains

    NARCIS (Netherlands)

    K. Inderfurth (Karl); R.H. Teunter (Ruud)

    2001-01-01

    textabstractMore and more supply chains emerge that include a return flow of materials. Many original equipment manufacturers are nowadays engaged in the remanufacturing business. In many process industries, production defectives and by-products are reworked. These closed-loop supply chains deserve

  16. Juvenile offenders: competence to stand trial.

    Science.gov (United States)

    Soulier, Matthew

    2012-12-01

    This article details the legal background and assists the reader in the preparation and practical conduct of evaluations regarding juvenile adjudicative competency. The material is presented to be useful as a guide to direct questions of competency and covers aspects of evaluation that include: legal standard for competency to stand trial, developmental immaturity, current practice in juvenile competency to stand trial, forensic evaluation of juvenile competency to stand trial, organizing the evaluation, collateral sources of information, psychiatric evaluation of juvenile adjudicative competency, assessment of mental disorder and intellectual disability, assessment of developmental status, assessment of functional abilities for adjudicative competence, and reaching the forensic opinion. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. The OPERA trial: protocol for a randomised trial of an exercise intervention for older people in residential and nursing accommodation

    Directory of Open Access Journals (Sweden)

    Taylor Stephanie

    2011-02-01

    Full Text Available Abstract Background Depression is common in residents of Residential and Nursing homes (RNHs. It is usually undetected and often undertreated. Depression is associated with poor outcomes including increased morbidity and mortality. Exercise has potential to improve depression, and has been shown in existing trials to improve outcomes among younger and older people. Existing evidence comes from trials that are short, underpowered and not from RNH settings. The aim of the OPERA trial is to establish whether exercise is effective in reducing the prevalence of depression among older RNH residents. Method OPERA is a cluster randomised controlled trial. RNHs are randomised to one of two groups with interventions lasting 12 months Intervention group: a depression awareness and physical activity training session for care home staff, plus a whole home physical activation programme including twice weekly physiotherapist-led exercise groups. The intervention lasts for one year from randomisation, or Control group: a depression awareness training session for care home staff. Participants are people aged 65 or over who are free of severe cognitive impairment and willing to participate in the study. Our primary outcome is the prevalence of depressive symptoms, a GDS-15 score of five or more, in all participants at the end of the one year intervention period. Our secondary depression outcomes include remission of depressive symptoms and change in GDS-15 scores in those with depressive symptoms prior to randomisation. Other secondary outcomes include, fear of falling, mobility, fractures, pain, cognition, costs and health related quality of life. We aimed to randomise 77 RNHs. Discussion Home recruitment was completed in May 2010; 78 homes have been randomised. Follow up will finish in May 2011 and results will be available late 2011. Trial Registration [ISRCTN: ISRCTN43769277

  18. Sinus tarsi approach (STA) versus extensile lateral approach (ELA) for treatment of closed displaced intra-articular calcaneal fractures (DIACF): A meta-analysis.

    Science.gov (United States)

    Bai, L; Hou, Y-L; Lin, G-H; Zhang, X; Liu, G-Q; Yu, B

    2018-04-01

    Our aim was to compare the effect of sinus tarsi approach (STA) vs extensile lateral approach (ELA) for treatment of closed displaced intra-articular calcaneal fractures (DIACF) is still being debated. A thorough research was carried out in the MEDLINE, EMBASE and Cochrane library databases from inception to December 2016. Only prospective or retrospective comparative studies were selected in this meta-analysis. Two independent reviewers conducted literature search, data extraction and quality assessment. The primary outcomes were anatomical restoration and prevalence of complications. Secondary outcomes included operation time and functional recovery. Four randomized controlled trials involving 326 patients and three cohort studies involving 206 patients were included. STA technique for DIACFs led to a decline in both operation time and incidence of complications. There were no significant differences between the groups in American Orthopedic Foot and Ankle Society scores, nor changes in Böhler angle. This meta-analysis suggests that STA technique may reduce the operation time and incidence of complications. In conclusion, STA technique is reasonably an optimal choice for DIACF. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  19. Results of an Oncology Clinical Trial Nurse Role Delineation Study.

    Science.gov (United States)

    Purdom, Michelle A; Petersen, Sandra; Haas, Barbara K

    2017-09-01

    To evaluate the relevance of a five-dimensional model of clinical trial nursing practice in an oncology clinical trial nurse population. 
. Web-based cross-sectional survey.
. Online via Qualtrics.
. 167 oncology nurses throughout the United States, including 41 study coordinators, 35 direct care providers, and 91 dual-role nurses who provide direct patient care and trial coordination.
. Principal components analysis was used to determine the dimensions of oncology clinical trial nursing practice.
. Self-reported frequency of 59 activities.
. The results did not support the original five-dimensional model of nursing care but revealed a more multidimensional model.
. An analysis of frequency data revealed an eight-dimensional model of oncology research nursing, including care, manage study, expert, lead, prepare, data, advance science, and ethics.
. This evidence-based model expands understanding of the multidimensional roles of oncology nurses caring for patients with cancer enrolled in clinical trials.

  20. Pressure tube rupture in a closed tank

    International Nuclear Information System (INIS)

    Khater, H.A.; Hadaller, G.I.; Stern, F.

    1985-06-01

    A study has been prepared on the feasibility of conducting pressure tube/calandria tube rupture tests in a closed tank, simulating a scaled-down calandria vessel. The study includes: i) a review of previous work, ii) an analytical investigation of the scaling problem of the calandria vessel and relevant in-core structures, iii) selection of a method for initiating pressure tube/calandria tube rupture, iv) a set of specifications for the test assembly, v) general arrangement drawings, vi) a proposal for a test matrix, vii) a survey and evaluation of existing facilities which could provide the required high pressure, temperature and fluid inventory, and viii) a cost estimate for the detailed design and construction, instrumentation, data acquisition and reduction, testing and reporting. The study concludes that it is both technically and practically feasible to conduct pressure tube rupture tests in a closed tank

  1. Restaurants closed over Christmas

    CERN Multimedia

    2011-01-01

    The restaurants will be closed during the Christmas holiday period : please note that all three CERN Restaurants will be closed from 5 p.m. on Wednesday, 21 December until Wednesday, 4 January inclusive. The Restaurants will reopen on Thursday, 5 January 2012.

  2. The Healthy Heart-Mind trial: melatonin for prevention of delirium following cardiac surgery: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Ford, Andrew H; Flicker, Leon; Passage, Jurgen; Wibrow, Bradley; Anstey, Matthew; Edwards, Mark; Almeida, Osvaldo P

    2016-01-28

    Delirium is a common occurrence in patients undergoing major cardiac surgery and is associated with a number of adverse consequences for the individual, their family and the health system. Current approaches to the prevention of delirium include identifying those at risk together with various non-pharmacological and pharmacological strategies, although the efficacy of these is often modest. Emerging evidence suggests that melatonin may be biologically implicated in the development of delirium and that melatonin supplementation may be beneficial in reducing the incidence of delirium in medical and surgical patients. We designed this trial to determine whether melatonin reduces the incidence of delirium following cardiac surgery compared with placebo. The Healthy Heart-Mind trial is a randomized, double-blind, placebo-controlled clinical trial of 3 mg melatonin or matching placebo administered on seven consecutive days for the prevention of delirium following cardiac surgery. We will recruit 210 adult participants, aged 50 and older, undergoing elective or semi-elective cardiac surgery with the primary outcome of interest for this study being the difference in the incidence of delirium between the groups within 7 days of surgery. Secondary outcomes of interest include the difference between groups in the severity and duration of delirious episodes, hospital length of stay and referrals to mental health services during admission. In addition, we will assess differences in depressive and anxiety symptoms, as well as cognitive performance, at discharge and 3 months after surgery. The results of this trial will clarify whether melatonin reduces the incidence of delirium following cardiac surgery. The trial is registered with the Australian Clinical Trials Registry, trial number ACTRN12615000819527 (10 August 2015).

  3. Remune trial will stop; new trials planned.

    Science.gov (United States)

    James, J S

    1999-05-21

    A clinical trial using remune, the anti-HIV vaccine developed by the late Dr. Jonas Salk, has been ended. The study is a clinical-endpoint trial which looks for statistically significant differences in AIDS sickness or death between patients who add remune to their treatment regimens versus those who use a placebo. Agouron Pharmaceuticals and the Immune Response Corporation who were conducting the trial announced their decision to stop it after an analysis by the Data Safety Monitoring Board. No differences in clinical endpoints were found and it was projected that continuing the trial would likely not find any. The companies are now planning two new Phase III trials using viral load testing rather than clinical endpoints as study criteria.

  4. The effect of closed channels on the electron impact excitation of Mg +, Cd + ions

    Science.gov (United States)

    Li, Yueming

    2018-04-01

    Based on the developed method for solving the multi-channel equation, which had been applied to the calculations of several kinds of ions including only open-open interactions, closed channels and their interactions with open channels have been studied. The wave functions of the closed channels are also expressed in terms of their homogeneous solutions which is just the same as for open channels. The homogeneous solutions are described and solved in WKB form, therefore the regular and irregular solutions as well as the quantum defect numbers can be obtained simultaneously. Excitations of Mg +, Cd + ions impact by electrons are calculated for energies close to the thresholds. The results are compared with those of the experimental observations and previous theoretical calculations. The effect of including the closed channels, especially when the energy passes through the resonance energies, has been discussed according to the deduced formulae and the calculated results.

  5. Clinical Trials

    Medline Plus

    Full Text Available ... of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a key ... Enterprise NHLBI has a strong tradition of supporting clinical trials that have not only shaped medical practice around the world, but have improved the health ...

  6. A randomised comparison of radical radiotherapy with or without chemotherapy for patients with non-small cell lung cancer: Results from the Big Lung Trial

    International Nuclear Information System (INIS)

    Fairlamb, David; Milroy, Robert; Gower, Nicole; Parmar, Mahesh; Peake, Michael; Rudd, Robin; Souhami, Robert; Spiro, Stephen; Stephens, Richard; Waller, David

    2005-01-01

    Background: A meta-analysis of trials comparing primary treatment with or without chemotherapy for patients with non-small cell lung cancer published in 1995 suggested a survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings studied, but it included many small trials, and trials with differing eligibility criteria and chemotherapy regimens. Methods: The Big Lung Trial was a large pragmatic trial designed to confirm the survival benefits seen in the meta-analysis, and this paper reports the findings in the radical radiotherapy setting. The trial closed before the required sample size was achieved due to slow accrual, with a total of 288 patients randomised to receive radical radiotherapy alone (146 patients) or sequential radical radiotherapy and cisplatin-based chemotherapy (142 patients). Results: There was no evidence that patients allocated sequential chemotherapy and radical radiotherapy had a better survival than those allocated radical radiotherapy alone, HR 1.07 (95% CI 0.84-1.38, P=0.57), median survival 13.0 months for the sequential group and 13.2 for the radical radiotherapy alone group. In addition, exploratory analyses could not identify any subgroup that might benefit more or less from chemotherapy. Conclusions: Despite not suggesting a survival benefit for the sequential addition of chemotherapy to radical radiotherapy, possibly because of the relatively small sample size and consequently wide confidence intervals, the results can still be regarded as consistent with the meta-analysis, and other similarly designed recently published large trials. Combining all these results suggests there may be a small median survival benefit with chemotherapy of between 2 and 8 weeks

  7. Involving South Asian patients in clinical trials.

    Science.gov (United States)

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

    2004-10-01

    To investigate how South Asian patients conceptualise the notion of clinical trials and to identify key processes that impact on trial participation and the extent to which communication difficulties, perceptions of risk and attitudes to authority influence these decisions. Also to identify whether 'South Asian' patients are homogeneous in these issues, and which factors differ between different South Asian subgroups and finally how professionals regard the involvement of South Asian patients and their views on strategies to increase participation. A review of the literature on minority ethnic participation in clinical trials was followed by three qualitative interview studies. Interviews were taped and transcribed (and translated if required) and subjected to framework analysis. Face-to-face interviews were conducted with 25 health professionals; 60 South Asian lay people who had not taken part in a trial and 15 South Asian trial participants. Motivations for trial participation were identified as follows: to help society, to improve own health or that of family and friends, out of obligation to the doctor and to increase scientific knowledge. Deterrents were concerns about drug side-effects, busy lifestyles, language, previous bad experiences, mistrust and feelings of not belonging to British society. There was no evidence of antipathy amongst South Asians to the concept of clinical trials and, overall, the younger respondents were more knowledgeable than the older ones. Problems are more likely to be associated with service delivery. Lack of being approached was a common response. Lay-reported factors that might affect South Asian participation in clinical trials include age, language, social class, feeling of not belonging/mistrust, culture and religion. Awareness of clinical trials varied between each group. There are more similarities than differences in attitudes towards clinical trial participation between the South Asian and the general population

  8. Design of clinical trials for therapeutic cancer vaccines development.

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

  9. Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT

    Directory of Open Access Journals (Sweden)

    Huisjes Anjoke JM

    2007-07-01

    Full Text Available Abstract Background Around 80% of intrauterine growth restricted (IUGR infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. Methods/design The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ. Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term. The study aims to include 325 patients per arm. Discussion This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term. Trial registration Dutch Trial Register and ISRCTN

  10. Clinical trial participation. Viewpoints from racial/ethnic groups.

    Science.gov (United States)

    Roberson, N L

    1994-11-01

    Racial/ethnic groups' participation in clinical trials is a relatively new area of research that warrants attention. Although racial/ethnic groups have been included in experimental studies since the 1940s, they were not included in significant numbers in clinical trials for cancer. Clinical trials play a dominant role in clinical oncology. Despite this state-of-the-art cancer treatment, however, there is mounting concern that this scientific progress is not being shared equitably by all segments of the U.S. population. There is underrepresentation of members of racial/ethnic groups in cancer clinical trials, which suggests that participation may be a critical issue. Unfortunately, little is known or documented about these groups' participation in clinical trials. This paper discusses racial/ethnic groups' views and opinions about clinical trial participation. Diagnostic research was conducted as a beginning phase to investigate this new area of research. African Americans, Hispanics, and Native Americans in three Buffalo, New York, communities were selected as study subjects. Data were collected via telephone surveys. Qualitative methods were employed for data analysis and reporting. Findings showed that study subjects knew little about cancer clinical trials and basically had no opportunity to participate. They believed that participation in clinical trials could be beneficial. In each of the three groups, however, there were cultural factors believed to influence participation. A primary concern was "mistrust of white people" and the feeling of being treated like "guinea pigs." Based on study findings, it was evident that recruitment for improving participation requires strategic planning that involves participants representative of the study population. To yield results, the plan should be tailored to the target group, presented as a credible study, designed to reflect trust in the medical care team, and implemented through a continuous educational process.

  11. High Cable Forces Deteriorate Pinch Force Control in Voluntary-Closing Body-Powered Prostheses.

    Directory of Open Access Journals (Sweden)

    Mona Hichert

    Full Text Available It is generally asserted that reliable and intuitive control of upper-limb prostheses requires adequate feedback of prosthetic finger positions and pinch forces applied to objects. Body-powered prostheses (BPPs provide the user with direct proprioceptive feedback. Currently available BPPs often require high cable operation forces, which complicates control of the forces at the terminal device. The aim of this study is to quantify the influence of high cable forces on object manipulation with voluntary-closing prostheses.Able-bodied male subjects were fitted with a bypass-prosthesis with low and high cable force settings for the prehensor. Subjects were requested to grasp and transfer a collapsible object as fast as they could without dropping or breaking it. The object had a low and a high breaking force setting.Subjects conducted significantly more successful manipulations with the low cable force setting, both for the low (33% more and high (50% object's breaking force. The time to complete the task was not different between settings during successful manipulation trials.High cable forces lead to reduced pinch force control during object manipulation. This implies that low cable operation forces should be a key design requirement for voluntary-closing BPPs.

  12. Practical considerations for adaptive trial design and implementation

    CERN Document Server

    Pinheiro, José; Kuznetsova, Olga

    2014-01-01

    This edited volume is a definitive text on adaptive clinical trial designs from creation and customization to utilization. As this book covers the full spectrum of topics involved in the adaptive designs arena, it will serve as a valuable reference for researchers working in industry, government and academia. The target audience is anyone involved in the planning and execution of clinical trials, in particular, statisticians, clinicians, pharmacometricians, clinical operation specialists, drug supply managers, and infrastructure providers.  In spite of the increased efficiency of adaptive trials in saving costs and time, ultimately getting drugs to patients sooner, their adoption in clinical development is still relatively low.  One of the chief reasons is the higher complexity of adaptive design trials as compared to traditional trials. Barriers to the use of clinical trials with adaptive features include the concerns about the integrity of study design and conduct, the risk of regulatory non-acceptance, t...

  13. Minding the close relationship.

    Science.gov (United States)

    Harvey, J H; Omarzu, J

    1997-01-01

    In this theoretical analysis, we argue that a process referred to as minding is essential for a couple to feel mutually close and satisfied in a close relationship over a long period Minding represents a package of mutual self-disclosure, other forms of goal-oriented behavior aimed at facilitating the relationship, and attributions about self's and other's motivations, intentions, and Mort in the relationship. Self-disclosure and attribution activities in minding are aimed at getting to know the other, trying to understand the other's motivations and deeper disposition as they pertain to the relationship, and showing respect and acceptance for knowledge gained about other. We link the concept of minding to other major ideas and literatures about how couples achieve closeness: self-disclosure and social penetration, intimacy, empathy and empathic accuracy, and love and self-expansion. We argue that the minding process articulated here has not previously been delineated and that it is a useful composite notion about essential steps in bonding among humans. We also argue that the minding concept stretches our understanding of the interface of attribution and close relationships. We present research possibilities and implications and consider possible alternative positions and counter arguments about the merits of the minding idea for close relationship satisfaction.

  14. Study design issues in trials among children with MAM

    International Nuclear Information System (INIS)

    Friis, Henrik

    2014-01-01

    There is a need for acceptable and affordable food aid products for children with moderate acute malnutrition (MAM), which effectively restore body tissues and functions. The effects of potential products need to be assessed through randomised controlled trials (RCT). However, nutritional RCTs pose ethical and scientific challenges. Control groups are usually given “standard of care”, but recommendations for treatment do not exist in all settings or supplements are not always available. In places where treatment is nonexistent, not giving any food to children in the control group is not without ethical concerns. However, from public health and scientific perspectives, it is problematic to compare with supplements which are not recommended or the effect of which is unknown. Firstly, it is of questionable value for a low-income country that a trial is conducted to compare an experimental supplement to a supplement that is not already standard of care, and national ethics committees may not grant permission for such a trial. Secondly, it is difficult to interpret findings from a trial comparing an experimental supplement to one that has not been properly tested. Hence, where supplementation is not standard of care, it may be ethically justifiable to have an unsupplemented control group. In such cases, mothers should receive health education and the children should receive medical attention, be monitored closely, and referred for further medical examination and treatment if not recovering. Delayed supplementation may also be considered. Food interventions are complex, since supplements with the same energy content may be based on different ingredients, and nutrients in different forms and amounts. Consequently, there are an infinite number of potential food supplements, yet only a few can be tested in trials. Some components may be potentially important, but costly. If several factors are of interest, then a factorial design may be needed. E.g. the treatFOOD trial

  15. Enrolling adolescents in HIV vaccine trials: reflections on legal complexities from South Africa.

    Science.gov (United States)

    Slack, Catherine; Strode, Ann; Fleischer, Theodore; Gray, Glenda; Ranchod, Chitra

    2007-05-13

    South Africa is likely to be the first country in the world to host an adolescent HIV vaccine trial. Adolescents may be enrolled in late 2007. In the development and review of adolescent HIV vaccine trial protocols there are many complexities to consider, and much work to be done if these important trials are to become a reality. This article sets out essential requirements for the lawful conduct of adolescent research in South Africa including compliance with consent requirements, child protection laws, and processes for the ethical and regulatory approval of research. This article outlines likely complexities for researchers and research ethics committees, including determining that trial interventions meet current risk standards for child research. Explicit recommendations are made for role-players in other jurisdictions who may also be planning such trials. This article concludes with concrete steps for implementing these important trials in South Africa and other jurisdictions, including planning for consent processes; delineating privacy rights; compiling information necessary for ethics committees to assess risks to child participants; training trial site staff to recognize when disclosures trig mandatory reporting response; networking among relevant ethics committees; and lobbying the National Regulatory Authority for guidance.

  16. Risk for banker’s connected to closing a customer’s account

    Directory of Open Access Journals (Sweden)

    Thibedi Majake

    2016-12-01

    Full Text Available Financial institutions (banks and building societies from time to time request customers to close their accounts and make alternative arrangements. This occurs most often if the financial institution is unhappy with the way in which the customer is using the account or it feels that its relationship with the customer has broken down irretrievably. Banks sometimes close a customer’s account without the customer’s agreement. Most other commercial organisations, banks and building societies included, are under no obligation to continue doing business with someone if they do not consider it appropriate to do so. However when financial institutions decide to close accounts of customers, this should not be on based on an improper reason – for instance, because of unfair bias or unlawful discrimination. And it is an implied term of the contract between the bank and its customer that the bank will not normally close the customer’s account without giving reasonable notice. This article seeks to analyse instances where banks have closed their customers’ accounts and factors that were considered, if any, for such a decision

  17. TV News Magazine Presentation: Close Up Gendai by NHK (2010)

    CERN Multimedia

    2011-01-01

    In this episode of Close Up Gendai, dark matter is the subject of investigation and one of the unsolved mysteries of the Universe. The show highlights the research being done around the globe to try to understand dark matter, including the research happening at the XMASS experiment in Japan, the Cryogenic Dark Matter Search experiment in the US, as well as CERN’s LHC experiments. Close Up Gendai will be presented on Friday, 8 April from 13:00 to 13:30 in the Council Chamber Language: Japanese  

  18. Close relatives find meaning to cope with cancer diagnosis and treatment of family members.

    Science.gov (United States)

    Feyh, Janelle M; Levine, Ellen G; Clay, Karine

    2012-12-01

    Pediatric palliative care has recently become a priority in the health care field and is implemented at the time of diagnosis rather than days or weeks before the child's death. Social constructivism theory in which humans generate meaning from their experiences was utilized as a general framework to determine the impact of pediatric palliative care on close relatives. The purpose of this grounded theory study was to generate a substantive theory that explains how close relatives such as grandparents, aunts, and uncles of a child with cancer experience palliative care. The participants of the study included close relatives of children in palliative care. Semistructured interviews and journaling were used to collect data. Initial, focused, and axial coding procedures were used to manage the data and a content analysis of the textual data was performed. Findings from the data suggested a process of finding meaning which helps close relatives to let go of what they cannot control while holding on to what they can control. Social change implications of this study may include improving health care programming for close relatives utilizing supportive-expressive measures. This programming may promote mental health of the close relatives who will learn to deal with their adjustment difficulties and improve their coping skills.

  19. Efficient elutriation of monocytes within a closed system (Elutra) for clinical-scale generation of dendritic cells.

    Science.gov (United States)

    Berger, Thomas G; Strasser, Erwin; Smith, Richard; Carste, Curt; Schuler-Thurner, Beatrice; Kaempgen, Eckhart; Schuler, Gerold

    2005-03-01

    Dendritic cells (DC) are promising tools for the immunotherapy of cancer. The induction of tumor-specific T cells and clinical regressions have already been observed in early phase I/II vaccination trials. As DC vaccination is now facing trials with larger patient collectives it becomes increasingly important to obtain large numbers of cells suitable for therapeutic applications under labor- and cost-effective conditions. We describe here a procedure that uses a novel cell separator (Elutra, Gambro BCT) to enrich monocytes from an entire apheresis product within one hour. Cells are separated on the basis of size and to a lesser extent density, by elutriation in a 40-ml conical chamber. The total monocyte recovery following elutriation (n = 6) was 98.53% (+/-8.07%), the recovery in the monocyte-rich fraction 75.45% (+/-11.31%), and the mean purity 82.95% (+/-6.01%). These monocytes can be cultured either in conventional culture dishes or in closed cell culture bags and differentiated, by using GM-CSF+IL-4 followed by a maturation cocktail composed of IL-1beta+IL-6+TNF-alpha+PGE2, into fully mature DC. The Elutra separator allows for fast and easy enrichment of monocytes within a closed system. Subsequently, elutriated monocytes can be successfully cultured into phenotypically and functionally mature DC for immunotherapeutic approaches. The method neither requires a density gradient step to enrich PBMC from leucapheresis products nor does it apply (xenogeneic) antibodies to target monocytes. Isolation of monocytes with Elutra may greatly facilitate future DC-based vaccination approaches.

  20. Clinical Trials

    Medline Plus

    Full Text Available ... clinical trials. If you're thinking about taking part in a clinical trial, find out ahead of time about costs and coverage. You should learn about the risks and benefits of any clinical trial before you agree to take part in the trial. Talk with your doctor about ...

  1. 7 CFR 764.402 - Loan closing.

    Science.gov (United States)

    2010-01-01

    ... SPECIAL PROGRAMS DIRECT LOAN MAKING Loan Decision and Closing § 764.402 Loan closing. (a) Signature... information for the Agency to reconfirm approval and proceed with loan closing. (3) The Agency or closing... account will be used according to subpart B of part 761 of this chapter when these processes are not...

  2. Study of neurontin: titrate to effect, profile of safety (STEPS) trial: a narrative account of a gabapentin seeding trial.

    Science.gov (United States)

    Krumholz, Samuel D; Egilman, David S; Ross, Joseph S

    2011-06-27

    Seeding trials, clinical studies conducted by pharmaceutical companies for marketing purposes, have rarely been described in detail. We examined all documents relating to the clinical trial Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) produced during the Neurontin marketing, sales practices, and product liability litigation, including company internal and external correspondence, reports, and presentations, as well as depositions elicited in legal proceedings of Harden Manufacturing vs Pfizer and Franklin vs Warner-Lambert, most which were created between 1990 and 2009. Using a systematic search strategy, we identified and reviewed all documents related to the STEPS trial in order to identify key themes related to the trial's conduct and determine the extent of marketing involvement in its planning and implementation. Documents demonstrated that STEPS was a seeding trial posing as a legitimate scientific study. Documents consistently described the trial itself, not trial results, to be a marketing tactic in the company's marketing plans. Documents demonstrated that at least 2 external sources questioned the validity of the study before execution, and that data quality during the study was often compromised. Furthermore, documents described company analyses examining the impact of participating as a STEPS investigator on rates and dosages of gabapentin prescribing, finding a positive association. None of these findings were reported in 2 published articles. The STEPS trial was a seeding trial, used to promote gabapentin and increase prescribing among investigators, and marketing was extensively involved in its planning and implementation.

  3. New EORTC clinical trials for BNCT

    International Nuclear Information System (INIS)

    Hideghety, K.; Moss, R.; Vries, M. de

    2000-01-01

    Due to ethical reasons, a separated optimization of the two components of BNCT in the frame of clinical investigations can only be performed applying the whole binary system. The ongoing trial at HFR (High Flux Reactor Petten) has proven the feasibility of BNCT under defined conditions. On that basis the European Commission supported a comprehensive research project on boron imaging including three further clinical studies. In the first trial the boron uptake related to the blood boron concentration and surrounding normal tissue in various solid tumours will be examined using BSH (Sodiumborocaptate), BPA (Boronophenylalanine) or both in order to explore tumour entities, which may gain benefit from BNCT. The major objectives of the second trial are to define the maximum tolerated single and cumulative dose, and the dose limiting toxicity of BSH. The third clinical trial, a phase II study is designed to evaluate the anti-tumour effect of fractionated BNCT at the Petten treatment facility against cerebral metastasis of malignant melanoma using BPA. (author)

  4. Conducting feasibilities in clinical trials: An investment to ensure a good study

    Directory of Open Access Journals (Sweden)

    Viraj Rajadhyaksha

    2010-01-01

    Full Text Available Conducting clinical trial feasibility is one of the first steps in clinical trial conduct. This process includes assessing internal and environmental capacity, alignment of the clinical trial in terms of study design, dose of investigational product, comparator, patient type, with the local environment and assessing potential of conducting clinical trial in a specific country. A robust feasibility also ensures a realistic assessment and capability to conduct the clinical trial. For local affiliates of pharmaceutical organizations, and contract research organizations, this is a precursor to study placement and influences the decision of study placement. This article provides details on different types of feasibilities, information which is to be included and relevance of each. The article also aims to provide practical hands-on suggestions to make feasibilities more realistic and informative.

  5. Conducting feasibilities in clinical trials: an investment to ensure a good study.

    Science.gov (United States)

    Rajadhyaksha, Viraj

    2010-07-01

    Conducting clinical trial feasibility is one of the first steps in clinical trial conduct. This process includes assessing internal and environmental capacity, alignment of the clinical trial in terms of study design, dose of investigational product, comparator, patient type, with the local environment and assessing potential of conducting clinical trial in a specific country. A robust feasibility also ensures a realistic assessment and capability to conduct the clinical trial. For local affiliates of pharmaceutical organizations, and contract research organizations, this is a precursor to study placement and influences the decision of study placement. This article provides details on different types of feasibilities, information which is to be included and relevance of each. The article also aims to provide practical hands-on suggestions to make feasibilities more realistic and informative.

  6. Clinical Trials

    Medline Plus

    Full Text Available ... need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in ... Maryland, runs clinical trials. Many other clinical trials take place in medical centers and ... trial can have many benefits. For example, you may gain access to new treatments before ...

  7. A multidisciplinary study of a small, temporarily open/closed South ...

    African Journals Online (AJOL)

    In 2005/2006 a multidisciplinary research programme that included studies on the hydrodynamics, sediment dynamics, macronutrients, microalgae, macrophytes, zoobenthos, hyperbenthos, zooplankton, ichthyoplankton, fish and birds of the temporarily open/closed East Kleinemonde Estuary was conducted. Particular ...

  8. Off-Shell Interactions of Closed-String Tachyons

    Energy Technology Data Exchange (ETDEWEB)

    Dabholkar, A

    2004-04-07

    Off-shell interactions for localized closed-string tachyons in C/Z{sub N} superstring backgrounds are analyzed and a conjecture for the effective height of the tachyon potential is elaborated. At large N, some of the relevant tachyons are nearly massless and their interactions can be deduced from the S-matrix. The cubic interactions between these tachyons and the massless fields are computed in a closed form using orbifold CFT techniques. The cubic interaction between nearly-massless tachyons with different charges is shown to vanish and thus condensation of one tachyon does not source the others. It is shown that to leading order in N, the quartic contact interaction vanishes and the massless exchanges completely account for the four point scattering amplitude. This indicates that it is necessary to go beyond quartic interactions or to include other fields to test the conjecture for the height of the tachyon potential.

  9. A machine learning approach to identify clinical trials involving nanodrugs and nanodevices from ClinicalTrials.gov.

    Directory of Open Access Journals (Sweden)

    Diana de la Iglesia

    Full Text Available Clinical Trials (CTs are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano, and CTs that do not involve nanotechnology (non-nano. Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs-even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results.We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i extraction and manual annotation of CTs as nano vs. non-nano, ii pre-processing and automatic classification, and iii performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset.The performance of the best automated classifier closely matches that of experts (AUC over 0.95, suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a particular nanoparticle or nanodevice

  10. A machine learning approach to identify clinical trials involving nanodrugs and nanodevices from ClinicalTrials.gov.

    Science.gov (United States)

    de la Iglesia, Diana; García-Remesal, Miguel; Anguita, Alberto; Muñoz-Mármol, Miguel; Kulikowski, Casimir; Maojo, Víctor

    2014-01-01

    Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano), and CTs that do not involve nanotechnology (non-nano). Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs-even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results. We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i) extraction and manual annotation of CTs as nano vs. non-nano, ii) pre-processing and automatic classification, and iii) performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset. The performance of the best automated classifier closely matches that of experts (AUC over 0.95), suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a particular nanoparticle or nanodevice, which is

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

    Science.gov (United States)

    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.

  12. Clinical trials in dentistry in India: Analysis from trial registry.

    Science.gov (United States)

    Gowri, S; Kannan, Sridharan

    2017-01-01

    Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy

  13. Closed-Loop Process Control for Electron Beam Freeform Fabrication and Deposition Processes

    Science.gov (United States)

    Taminger, Karen M. (Inventor); Hafley, Robert A. (Inventor); Martin, Richard E. (Inventor); Hofmeister, William H. (Inventor)

    2013-01-01

    A closed-loop control method for an electron beam freeform fabrication (EBF(sup 3)) process includes detecting a feature of interest during the process using a sensor(s), continuously evaluating the feature of interest to determine, in real time, a change occurring therein, and automatically modifying control parameters to control the EBF(sup 3) process. An apparatus provides closed-loop control method of the process, and includes an electron gun for generating an electron beam, a wire feeder for feeding a wire toward a substrate, wherein the wire is melted and progressively deposited in layers onto the substrate, a sensor(s), and a host machine. The sensor(s) measure the feature of interest during the process, and the host machine continuously evaluates the feature of interest to determine, in real time, a change occurring therein. The host machine automatically modifies control parameters to the EBF(sup 3) apparatus to control the EBF(sup 3) process in a closed-loop manner.

  14. Establishing guidelines for pharmacotherapy trials in bulimia nervosa and anorexia nervosa.

    Science.gov (United States)

    Mitchell, J E; Tareen, B; Sheehan, W; Agras, S; Brewerton, T D; Crow, S; Devlin, M; Eckert, E; Halmi, K; Herzog, D; Marcus, M; Powers, P; Stunkard, A; Walsh, B T

    2000-07-01

    This paper addresses the lack of a standard protocol for pharmacotherapy trials for patients with bulimia nervosa (BN) and anorexia nervosa (AN). Twenty-two surveys were sent to established researchers in the field of eating disorders to elicit their opinions regarding medication trials, including baseline laboratory tests, the optimal length/frequency of medication management sessions, and the information that should or should not be included in these sessions. Sixteen of 22 researchers completed and returned the survey. Their answers are the basis of the data presented. We propose a battery of screening laboratory tests for both conditions. We suggest 30-45-min initial medication management sessions in both AN and BN trials with 15-min follow-ups to be held weekly for AN subjects, and weekly for 2 weeks, then biweekly for 2 weeks, then monthly, for BN subjects. We also recommend that published trials should include explicit details of medication management. Copyright 2000 John Wiley & Sons, Inc.

  15. Design and rationale of the Procalcitonin Antibiotic Consensus Trial (ProACT), a multicenter randomized trial of procalcitonin antibiotic guidance in lower respiratory tract infection.

    Science.gov (United States)

    Huang, David T; Angus, Derek C; Chang, Chung-Chou H; Doi, Yohei; Fine, Michael J; Kellum, John A; Peck-Palmer, Octavia M; Pike, Francis; Weissfeld, Lisa A; Yabes, Jonathan; Yealy, Donald M

    2017-08-29

    Overuse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns. The Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection. We describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation. ClinicalTrials.gov NCT02130986 . Registered May 1, 2014.

  16. Advances in Clinical Cardiology 2016: A Summary of the Key Clinical Trials.

    Science.gov (United States)

    Gray, Alastair; McQuillan, Conor; Menown, Ian B A

    2017-07-01

    The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA). Selection criteria were trials with a broad relevance to the cardiology community and those with potential to change current practice. A total of 57 key cardiology clinical trials were identified for inclusion. Here we describe and place in clinical context the key findings of new data relating to interventional and structural cardiology including delayed stenting following primary angioplasty, contrast-induced nephropathy, management of jailed wires, optimal duration of dual antiplatelet therapy (DAPT), stenting vs bypass for left main disease, new generation stents (BioFreedom, Orsiro, Absorb), transcatheter aortic valve implantation (Edwards Sapien XT, transcatheter embolic protection), and closure devices (Watchman, Amplatzer). New preventative cardiology data include trials of bariatric surgery, empagliflozin, liraglutide, semaglutide, PCSK9 inhibitors (evolocumab and alirocumab), and inclisiran. Antiplatelet therapy trials include platelet function monitoring and ticagrelor vs clopidogrel for peripheral vascular disease. New data are also presented in fields of heart failure (sacubitril/valsartan, aliskiren, spironolactone), atrial fibrillation (rivaroxaban in patients undergoing coronary intervention, edoxaban in DC cardioversion), cardiac devices (implantable cardioverter

  17. Virtual Close Quarter Battle (CQB) Graphical Decision Trainer

    Science.gov (United States)

    2002-09-01

    leave a gap in what would traditionally be thought of as an ideal locomotion device. Research has shown that the introduction of vestibular cues in...NAVAL POSTGRADUATE SCHOOL Monterey, California THESIS VIRTUAL CLOSE QUARTER BATTLE (CQB) GRAPHICAL DECISION TRAINER by Jordan Reece...including suggestions for reducing this burden, to Washington headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson

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

    Science.gov (United States)

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

    2017-05-25

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

  19. Cascaded recompression closed brayton cycle system

    Energy Technology Data Exchange (ETDEWEB)

    Pasch, James J.

    2018-01-02

    The present disclosure is directed to a cascaded recompression closed Brayton cycle (CRCBC) system and method of operation thereof, where the CRCBC system includes a compressor for compressing the system fluid, a separator for generating fluid feed streams for each of the system's turbines, and separate segments of a heater that heat the fluid feed streams to different feed temperatures for the system's turbines. Fluid exiting each turbine is used to preheat the fluid to the turbine. In an embodiment, the amount of heat extracted is determined by operational costs.

  20. Cascaded recompression closed brayton cycle system

    Science.gov (United States)

    Pasch, James J.

    2018-01-02

    The present disclosure is directed to a cascaded recompression closed Brayton cycle (CRCBC) system and method of operation thereof, where the CRCBC system includes a compressor for compressing the system fluid, a separator for generating fluid feed streams for each of the system's turbines, and separate segments of a heater that heat the fluid feed streams to different feed temperatures for the system's turbines. Fluid exiting each turbine is used to preheat the fluid to the turbine. In an embodiment, the amount of heat extracted is determined by operational costs.

  1. Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Mujagic, Edin; Zwimpfer, Tibor; Marti, Walter R; Zwahlen, Marcel; Hoffmann, Henry; Kindler, Christoph; Fux, Christoph; Misteli, Heidi; Iselin, Lukas; Lugli, Andrea Kopp; Nebiker, Christian A; von Holzen, Urs; Vinzens, Fabrizio; von Strauss, Marco; Reck, Stefan; Kraljević, Marko; Widmer, Andreas F; Oertli, Daniel; Rosenthal, Rachel; Weber, Walter P

    2014-05-24

    Surgical site infections are the most common hospital-acquired infections among surgical patients. The administration of surgical antimicrobial prophylaxis reduces the risk of surgical site infections . The optimal timing of this procedure is still a matter of debate. While most studies suggest that it should be given as close to the incision time as possible, others conclude that this may be too late for optimal prevention of surgical site infections. A large observational study suggests that surgical antimicrobial prophylaxis should be administered 74 to 30 minutes before surgery. The aim of this article is to report the design and protocol of a randomized controlled trial investigating the optimal timing of surgical antimicrobial prophylaxis. In this bi-center randomized controlled trial conducted at two tertiary referral centers in Switzerland, we plan to include 5,000 patients undergoing general, oncologic, vascular and orthopedic trauma procedures. Patients are randomized in a 1:1 ratio into two groups: one receiving surgical antimicrobial prophylaxis in the anesthesia room (75 to 30 minutes before incision) and the other receiving surgical antimicrobial prophylaxis in the operating room (less than 30 minutes before incision). We expect a significantly lower rate of surgical site infections with surgical antimicrobial prophylaxis administered more than 30 minutes before the scheduled incision. The primary outcome is the occurrence of surgical site infections during a 30-day follow-up period (one year with an implant in place). When assuming a 5% surgical site infection risk with administration of surgical antimicrobial prophylaxis in the operating room, the planned sample size has an 80% power to detect a relative risk reduction for surgical site infections of 33% when administering surgical antimicrobial prophylaxis in the anesthesia room (with a two-sided type I error of 5%). We expect the study to be completed within three years. The results of this

  2. Recruitment to publicly funded trials--are surgical trials really different?

    Science.gov (United States)

    Cook, Jonathan A; Ramsay, Craig R; Norrie, John

    2008-09-01

    Good recruitment is integral to the conduct of a high-quality randomised controlled trial. It has been suggested that recruitment is particularly difficult for evaluations of surgical interventions, a field in which there is a dearth of evidence from randomised comparisons. While there is anecdotal speculation to support the inference that recruitment to surgical trials is more challenging than for medical trials we are unaware of any formal assessment of this. In this paper, we compare recruitment to surgical and medical trials using a cohort of publicly funded trials. Overall recruitment to trials was assessed using of a cohort of publicly funded trials (n=114). Comparisons were made by using the Recruitment Index, a simple measure of recruitment activity for multicentre randomised controlled trials. Recruitment at the centre level was also investigated through three example surgical trials. The Recruitment Index was found to be higher, though not statistically significantly, in the surgical group (n=18, median=38.0 IQR (10.7, 77.4)) versus (n=81, median=34.8 IQR (11.7, 98.0)) days per recruit for the medical group (median difference 1.7 (-19.2, 25.1); p=0.828). For the trials where the comparison was between a surgical and a medical intervention, the Recruitment Index was substantially higher (n=6, 68.3 (23.5, 294.8)) versus (n=93, 34.6 (11.7, 90.0); median difference 25.9 (-35.5, 221.8); p=0.291) for the other trials. There was no clear evidence that surgical trials differ from medical trials in terms of recruitment activity. There was, however, support for the inference that medical versus surgical trials are more difficult to recruit to. Formal exploration of the recruitment data through a modelling approach may go some way to tease out where important differences exist.

  3. The COLOFOL trial

    DEFF Research Database (Denmark)

    Hansdotter Andersson, Pernilla; Wille-Jørgensen, Peer; Horváth-Puhó, Erzsébet

    2016-01-01

    population. To be eligible, patients had to be 75 years or younger and curatively resected for stage II or III colorectal cancer. Exclusion criteria were hereditary colorectal cancer, no signed consent, other malignancy, and life expectancy less than 2 years due to concomitant disease. In four of the 24......INTRODUCTION: The COLOFOL trial, a prospective randomized multicenter trial comparing two follow-up regimes after curative surgical treatment for colorectal cancer, focuses on detection of asymptomatic recurrences. This paper aims to describe the design and recruitment procedure in the COLOFOL...... participating centers, we scrutinized hospital inpatient data to identify all colorectal cancer patients who underwent surgery, in order to ascertain all eligible patients who were not included in the study and to compare them with enrolled patients. RESULTS: Of a total of 4,445 eligible patients, 2...

  4. Method and apparatus for controlling a powertrain system including a multi-mode transmission

    Science.gov (United States)

    Hessell, Steven M.; Morris, Robert L.; McGrogan, Sean W.; Heap, Anthony H.; Mendoza, Gil J.

    2015-09-08

    A powertrain including an engine and torque machines is configured to transfer torque through a multi-mode transmission to an output member. A method for controlling the powertrain includes employing a closed-loop speed control system to control torque commands for the torque machines in response to a desired input speed. Upon approaching a power limit of a power storage device transferring power to the torque machines, power limited torque commands are determined for the torque machines in response to the power limit and the closed-loop speed control system is employed to determine an engine torque command in response to the desired input speed and the power limited torque commands for the torque machines.

  5. Protocol of a cluster randomised stepped-wedge trial of behavioural interventions targeting amphetamine-type stimulant use and sexual risk among female entertainment and sex workers in Cambodia.

    Science.gov (United States)

    Page, Kimberly; Stein, Ellen S; Carrico, Adam W; Evans, Jennifer L; Sokunny, Muth; Nil, Ean; Ngak, Song; Sophal, Chhit; McCulloch, Charles; Maher, Lisa

    2016-05-09

    HIV risk among female entertainment and sex workers (FESW) remains high and use of amphetamine-type stimulants (ATS) significantly increases this risk. We designed a cluster randomised stepped wedge trial (The Cambodia Integrated HIV and Drug Prevention Implementation (CIPI) study) to test sequentially delivered behavioural interventions targeting ATS use. The trial combines a 12-week Conditional Cash Transfer (CCT) intervention with 4 weeks of cognitive-behavioural group aftercare (AC) among FESW who use ATS. The primary goal is to reduce ATS use and unprotected sex among FESW. The CCT+AC intervention is being implemented in 10 provinces where order of delivery was randomised. Outcome assessments (OEs) including biomarkers and self-reported measures of recent sexual and drug use behaviours are conducted prior to implementation, and at three 6-month intervals after completion. Consultation with multiple groups and stakeholders on implementation factors facilitated acceptance and operationalisation of the trial. Statistical power and sample size calculations were based on expected changes in ATS use and unprotected sex at the population level as well as within subjects. Ethical approvals were granted by the Cambodia National Ethics Committee; University of New Mexico; University of California, San Francisco; and FHI360. The trial is registered with ClinicalTrials.gov. Dissemination of process indicators during the multiyear trial is carried out through annual in-country Stakeholder Meetings. Provincial 'Close-Out' forums are held at the conclusion of data collection in each province. When analysis is completed, dissemination meetings will be held in Cambodia with stakeholders, including community-based discussion sessions, policy briefs and results published and presented in the HIV prevention scientific journals and conferences. CIPI is the first trial of an intervention to reduce ATS use and HIV risk among FESW in Cambodia. Will inform both CCT+AC implementation

  6. Recruitment of ethnic minorities into cancer clinical trials: experience from the front lines.

    Science.gov (United States)

    Symonds, R P; Lord, K; Mitchell, A J; Raghavan, D

    2012-09-25

    Throughout the world there are problems recruiting ethnic minority patients into cancer clinical trials. A major barrier to trial entry may be distrust of research and the medical system. This may be compounded by the regulatory framework governing research with an emphasis on written consent, closed questions and consent documentation, as well as fiscal issues. The Leicester UK experience is that trial accrual is better if British South Asian patients are approached by a senior doctor rather than someone of perceived lesser hierarchical status and a greater partnership between the hospital and General Practitioner may increase trial participation of this particular ethnic minority. In Los Angeles, USA, trial recruitment was improved by a greater utilisation of Hispanic staff and a Spanish language-based education programme. Involvement of community leaders is essential. While adhering to national, legal and ethnical standards, information sheets and consent, it helps if forms can be tailored towards the local ethnic minority population. Written translations are often of limited value in the recruitment of patients with no or limited knowledge of English. In some cultural settings, tape-recorded verbal consent (following approval presentations) may be an acceptable substitute for written consent, and appropriate legislative changes should be considered to facilitate this option. Approaches should be tailored to specific minority populations, taking consideration of their unique characteristics and with input from their community leadership.

  7. Chinese herbal medicine for cancer-related fatigue: a systematic review of randomized clinical trials.

    Science.gov (United States)

    Su, Chun-Xiang; Wang, Li-Qiong; Grant, Suzanne J; Liu, Jian-Ping

    2014-06-01

    To assess the effectiveness and safety of Chinese herbal medicine for the treatment of cancer-related fatigue. We systematically searched seven electronic databases and two trial registries for randomized clinical trials of Chinese herbal medicine for cancer-related fatigue. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool. Data were synthesized using RevMan 5.2 software. A total of 10 trials involving 751 participants with cancer-related fatigue were identified and the methodological quality of the included trials was generally poor. Chinese herbal medicine used alone or in combination with chemotherapy or supportive care showed significant relief in cancer-related fatigue compared to placebo, chemotherapy or supportive care based on single trials. Chinese herbal medicine plus chemotherapy or supportive care was superior to chemotherapy or supportive care in improving quality of life. Data from one trial demonstrated Chinese herbal medicine exerted a greater beneficial effect on relieving anxiety but no difference in alleviating depression. Seven trials reported adverse events and no severe adverse effects were found in Chinese herbal medicine groups. The findings from limited number of trials suggest that Chinese herbal medicine seems to be effective and safe in the treatment of cancer-related fatigue. However, the current evidence is insufficient to draw a confirmative conclusion due to the poor methodological quality of included trials. Thus, conducting rigorously designed trials on potential Chinese herbal medicine is warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

    Science.gov (United States)

    Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

    2012-07-01

    Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

  9. Protocol for the ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation trial: a pragmatic multi-centre randomised controlled trial of surgical versus non-surgical treatment for proximal fracture of the humerus in adults

    Directory of Open Access Journals (Sweden)

    Maffulli Nicola

    2009-11-01

    Full Text Available Abstract Background Proximal humeral fractures, which occur mainly in older adults, account for approximately 4 to 5% of all fractures. Approximately 40% of these fractures are displaced fractures involving the surgical neck. Management of this group of fractures is often challenging and the outcome is frequently unsatisfactory. In particular it is not clear whether surgery gives better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform this decision. Methods/Design We aim to undertake a pragmatic UK-based multi-centre randomised controlled trial evaluating the effectiveness and cost-effectiveness of surgical versus standard non-surgical treatment for adults with an acute closed displaced fracture of the proximal humerus with involvement of the surgical neck. The choice of surgical intervention is left to the surgeon, who must use techniques that they are fully experienced with. This will avoid 'learning curve' problems. We will promote good standards of non-surgical care, similarly insisting on care-provider competence, and emphasize the need for comparable provision of rehabilitation for both groups of patients. We aim to recruit 250 patients from a minimum of 18 NHS trauma centres throughout the UK. These patients will be followed-up for 2 years. The primary outcome is the Oxford Shoulder Score, which will be collected via questionnaires completed by the trial participants at 6, 12 and 24 months. This is a 12-item condition-specific questionnaire providing a total score based on the person's subjective assessment of pain and activities of daily living impairment. We will also collect data for other outcomes, including general health measures and complications, and for an economic evaluation. Additionally, we plan a systematic collection of reasons for non-inclusion of eligible patients who were not recruited into the trial, and their baseline

  10. 'Cloud computing' and clinical trials: report from an ECRIN workshop.

    Science.gov (United States)

    Ohmann, Christian; Canham, Steve; Danielyan, Edgar; Robertshaw, Steve; Legré, Yannick; Clivio, Luca; Demotes, Jacques

    2015-07-29

    Growing use of cloud computing in clinical trials prompted the European Clinical Research Infrastructures Network, a European non-profit organisation established to support multinational clinical research, to organise a one-day workshop on the topic to clarify potential benefits and risks. The issues that arose in that workshop are summarised and include the following: the nature of cloud computing and the cloud computing industry; the risks in using cloud computing services now; the lack of explicit guidance on this subject, both generally and with reference to clinical trials; and some possible ways of reducing risks. There was particular interest in developing and using a European 'community cloud' specifically for academic clinical trial data. It was recognised that the day-long workshop was only the start of an ongoing process. Future discussion needs to include clarification of trial-specific regulatory requirements for cloud computing and involve representatives from the relevant regulatory bodies.

  11. Effects of cognitive therapy versus interpersonal psychotherapy in patients with major depressive disorder: a systematic review of randomized clinical trials with meta-analyses and trial sequential analyses.

    Science.gov (United States)

    Jakobsen, J C; Hansen, J L; Simonsen, S; Simonsen, E; Gluud, C

    2012-07-01

    Major depressive disorder afflicts an estimated 17% of individuals during their lifetime at tremendous suffering and cost. Cognitive therapy and interpersonal psychotherapy are treatment options, but their effects have only been limitedly compared in systematic reviews. Using Cochrane systematic review methodology we compared the benefits and harm of cognitive therapy versus interpersonal psychotherapy for major depressive disorder. Trials were identified by searching the Cochrane Library's CENTRAL, Medline via PubMed, EMBASE, Psychlit, PsycInfo, and Science Citation Index Expanded until February 2010. Continuous outcome measures were assessed by mean difference and dichotomous outcomes by odds ratio. We conducted trial sequential analysis to control for random errors. We included seven trials randomizing 741 participants. All trials had high risk of bias. Meta-analysis of the four trials reporting data at cessation of treatment on the Hamilton Rating Scale for Depression showed no significant difference between the two interventions [mean difference -1.02, 95% confidence interval (CI) -2.35 to 0.32]. Meta-analysis of the five trials reporting data at cessation of treatment on the Beck Depression Inventory showed comparable results (mean difference -1.29, 95% CI -2.73 to 0.14). Trial sequential analysis indicated that more data are needed to definitively settle the question of a differential effect. None of the included trial reported on adverse events. Randomized trials with low risk of bias and low risk of random errors are needed, although the effects of cognitive therapy and interpersonal psychotherapy do not seem to differ significantly regarding depressive symptoms. Future trials should report on adverse events.

  12. Proactive recruitment of cancer patients’ social networks into a smoking cessation trial

    Science.gov (United States)

    Bastian, Lori A.; Fish, Laura J.; Peterson, Bercedis L.; Biddle, Andrea K.; Garst, Jennifer; Lyna, Pauline; Molner, Stephanie; Bepler, Gerold; Kelley, Mike; Keefe, Francis J.; McBride, Colleen M.

    2011-01-01

    Background This report describes the characteristics associated with successful enrollment of smokers in the social networks (i.e., family and close friends) of patients with lung cancer into a smoking cessation intervention. Methods Lung cancer patients from four clinical sites were asked to complete a survey enumerating their family members and close friends who smoke, and provide permission to contact these potential participants. Family members and close friends identified as smokers were interviewed and offered participation in a smoking cessation intervention. Repeated measures logistic regression model examined characteristics associated with enrollment. Results A total of 1,062 eligible lung cancer patients were identified and 516 patients consented and completed the survey. These patients identified 1,325 potentially eligible family and close friends. Of these, 496 consented and enrolled in the smoking cessation program. Network enrollment was highest among patients who were white and had late-stage disease. Social network members enrolled were most likely to be female, a birth family, immediate family, or close friend, and live in close geographic proximity to the patient. Conclusions Proactive recruitment of smokers in the social networks of lung cancer patients is challenging. In this study, the majority of family members and friends declined to participate. Enlisting immediate female family members and friends, who live close to the patient as agents to proactively recruit other network members into smoking cessation trials could be used to extend reach of cessation interventions to patients’ social networks. Moreover, further consideration should be given to the appropriate timing of approaching network smokers to consider cessation. PMID:21382509

  13. Quality of Life From Canadian Cancer Trials Group MA.17R: A Randomized Trial of Extending Adjuvant Letrozole to 10 Years

    Science.gov (United States)

    Brundage, Michael D.; Parulekar, Wendy R.; Goss, Paul E.; Ingle, James N.; Pritchard, Kathleen I.; Celano, Paul; Muss, Hyman; Gralow, Julie; Strasser-Weippl, Kathrin; Whelan, Kate; Tu, Dongsheng; Whelan, Timothy J.

    2018-01-01

    Purpose MA.17R was a Canadian Cancer Trials Group–led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor as adjuvant therapy for hormone receptor–positive breast cancer. Quality of life (QOL) was a secondary outcome measure of the study, and here, we report the results of these analyses. Methods QOL was measured using the Short Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months. QOL assessment was mandatory for Canadian Cancer Trials Group centers but optional for centers in other groups. Mean change scores from baseline were calculated. Results One thousand nine hundred eighteen women were randomly assigned, and 1,428 women completed the baseline QOL assessment. Compliance with QOL measures was > 85%. Baseline summary scores for the SF-36 physical component summary (47.5 for letrozole and 47.9 for placebo) and mental component summary (55.5 for letrozole and 54.8 for placebo) were close to the population norms of 50. No differences were seen between groups in mean change scores for the SF-36 physical and mental component summaries and the other eight QOL domains except for the role-physical subscale. No difference was found in any of the four domains of the MENQOL Conclusion No clinically significant differences were seen in overall QOL measured by the SF-36 summary measures and MENQOL between the letrozole and placebo groups. The data indicate that continuation of aromatase inhibitor therapy after 5 years of prior treatment in the trial population was not associated with a deterioration of overall QOL. PMID:29328860

  14. Quality of Life From Canadian Cancer Trials Group MA.17R: A Randomized Trial of Extending Adjuvant Letrozole to 10 Years.

    Science.gov (United States)

    Lemieux, Julie; Brundage, Michael D; Parulekar, Wendy R; Goss, Paul E; Ingle, James N; Pritchard, Kathleen I; Celano, Paul; Muss, Hyman; Gralow, Julie; Strasser-Weippl, Kathrin; Whelan, Kate; Tu, Dongsheng; Whelan, Timothy J

    2018-02-20

    Purpose MA.17R was a Canadian Cancer Trials Group-led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor as adjuvant therapy for hormone receptor-positive breast cancer. Quality of life (QOL) was a secondary outcome measure of the study, and here, we report the results of these analyses. Methods QOL was measured using the Short Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months. QOL assessment was mandatory for Canadian Cancer Trials Group centers but optional for centers in other groups. Mean change scores from baseline were calculated. Results One thousand nine hundred eighteen women were randomly assigned, and 1,428 women completed the baseline QOL assessment. Compliance with QOL measures was > 85%. Baseline summary scores for the SF-36 physical component summary (47.5 for letrozole and 47.9 for placebo) and mental component summary (55.5 for letrozole and 54.8 for placebo) were close to the population norms of 50. No differences were seen between groups in mean change scores for the SF-36 physical and mental component summaries and the other eight QOL domains except for the role-physical subscale. No difference was found in any of the four domains of the MENQOL Conclusion No clinically significant differences were seen in overall QOL measured by the SF-36 summary measures and MENQOL between the letrozole and placebo groups. The data indicate that continuation of aromatase inhibitor therapy after 5 years of prior treatment in the trial population was not associated with a deterioration of overall QOL.

  15. Quality of registration for clinical trials published in emergency medicine journals.

    Science.gov (United States)

    Jones, Christopher W; Platts-Mills, Timothy F

    2012-10-01

    In 2005, the International Committee of Medical Journal Editors established clinical trial registration as a requirement for articles submitted to member journals, with the goal of improving the transparency of clinical research. The objective of this study is to characterize the registration of clinical trials published in emergency medicine journals. Randomized trials involving human subjects and published between June 1, 2008, and May 31, 2011 in the 5 emergency medicine journals with the highest impact factors were included. We assessed the clarity of registered primary outcomes, timing of registration relative to patient enrollment, and consistency between registered and published outcomes. Of the 123 trials included, registry entries were identified for 57 (46%). Of the 57 registered studies, 45 (79%) were registered after the initiation of subject enrollment, 9 (16%) had registered outcomes that were unclear, and 26 (46%) had discrepancies between registered and published outcomes. Only 5 studies were registered before patient enrollment with a clear primary outcome that was consistent with the published primary outcome. Annals of Emergency Medicine was the only journal in which the majority of trials were registered. Current compliance with clinical trial registration guidelines is poor among trials published in emergency medicine journals. Copyright © 2012. Published by Mosby, Inc.

  16. Depression, anxiety and quality of life in suicide survivors: a comparison of close and distant relationships.

    Science.gov (United States)

    Mitchell, Ann M; Sakraida, Teresa J; Kim, Yookyung; Bullian, Leann; Chiappetta, Laurel

    2009-02-01

    The study's purpose was to describe and compare depression, anxiety, and quality of life, by degree of relationship, between closely related and distantly related survivors (persons close to the suicide victim, or "suicide survivors"; N = 60) during the acute phase of bereavement (within 1 month of the death). The close relationship category included spouses, parents, children, and siblings, whereas the distant relationship category included in-laws, aunts/uncles, and nieces/nephews. Analysis of covariance examined differences between the two groups on the symptom measures. Results indicate that, after controlling for age and gender effects, closely related survivors had significantly higher mean levels of depression and anxiety and had lower levels of mental health quality of life. There were no statistically significant differences on the physical health quality of life subscale.

  17. A systematic review of randomized controlled trials on exercise parameters in the treatment of patellofemoral pain: what works?

    Directory of Open Access Journals (Sweden)

    Kumar S

    2011-10-01

    Full Text Available Daniel Harvie, Timothy O'Leary, Saravana Kumar International Centre for Allied Health Evidence (iCAHE, City East Campus, University of South Australia, Adelaide, Australia Purpose: There is research evidence which supports the effectiveness of exercise in reducing pain and increasing function in patients with patellofemoral pain syndrome. However, what is unclear are the parameters underpinning this intervention. This has led to uncertainty when operationalizing exercises for patients with patellofemoral pain syndrome in clinical practice. The aim of this review was to evaluate the parameters of exercise programs reported in primary research, to provide clinicians with evidence-based recommendations for exercise prescription for patellofemoral pain. Methods: A systematic review of randomized controlled trials was undertaken. Only trials that identified exercise to be effective in treating patellofemoral pain were included. Appropriate databases and reference lists were searched using established keywords. Data relating to common exercise parameters such as the type of exercise, length, and frequency of intervention, intensity, repetitions, sets, and specific technique were extracted, along with details of co-interventions that may have been used. Results: A total of ten randomized controlled trials were included in this review and from these trials 14 interventions arms were evaluated. All 14 interventions focused on active exercises, all but two of which also included a passive stretching component. The current body of evidence demonstrates positive results with exercise interventions such as knee extension, squats, stationary cycling, static quadriceps, active straight leg raise, leg press, and step-up and down exercises for patients with patellofemoral pain syndrome. A progressive regime of daily exercises of two to four sets of ten or more repetitions over an intervention period of 6 weeks or more, combined with exercises to address

  18. Clinical Trials

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    Full Text Available ... Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, or ... and Clinical Studies Web page. Children and Clinical Studies Learn more about Children and Clinical Studies Importance ...

  19. Clinical Trials

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    Full Text Available ... more information about eligibility criteria, go to "How Do Clinical Trials Work?" Some trials enroll people who ... for adults. For more information, go to "How Do Clinical Trials Protect Participants?" For more information about ...

  20. Clinical Trials

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    Full Text Available ... or vulnerable patients (such as children). A DSMB's role is to review data from a clinical trial ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...

  1. Clinical Trials

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    Full Text Available ... clinical trials are vital to the process of improving medical care. Many people volunteer because they want ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find ...

  2. Clinical Trials

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    Full Text Available ... protocol affect the trial's results. Comparison Groups In most clinical trials, researchers use comparison groups. This means ... study before you agree to take part. Randomization Most clinical trials that have comparison groups use randomization. ...

  3. Clinical Trials

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... from a study at any time, for any reason. Also, during the trial, you have the right ...

  4. Clinical Trials

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    Full Text Available ... you agree to take part in the trial. Talk with your doctor about specific trials you're ... part in a clinical trial is your decision. Talk with your doctor about all of your treatment ...

  5. Clinical Trials

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    Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... study? How might this trial affect my daily life? Will I have to be in the hospital? ...

  6. Clinical Trials

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    Full Text Available ... any clinical trial before you agree to take part in the trial. Talk with your doctor about specific trials you're interested in. For a list of questions to ask your doctor and the ...

  7. Clinical Trials

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    Full Text Available ... or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research studies ... parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, doctors, nurses, ...

  8. Clinical Trials

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    Full Text Available ... under way. For example, some trials are stopped early if benefits from a strategy or treatment are ... stop a trial, or part of a trial, early if the strategy or treatment is having harmful ...

  9. ON NANO Λg-CLOSED SETS

    OpenAIRE

    Rajasekaran, Ilangovan; Nethaji, Ochanan

    2017-01-01

    Abstaract−In this paper, we introduce nano ∧g-closed sets in nano topological spaces. Some properties of nano ∧g-closed sets and nano ∧g-open sets are weaker forms of nano closed sets and nano open sets

  10. Developments in statistical evaluation of clinical trials

    CERN Document Server

    Oud, Johan; Ghidey, Wendimagegn

    2014-01-01

    This book describes various ways of approaching and interpreting the data produced by clinical trial studies, with a special emphasis on the essential role that biostatistics plays in clinical trials. Over the past few decades the role of statistics in the evaluation and interpretation of clinical data has become of paramount importance. As a result the standards of clinical study design, conduct and interpretation have undergone substantial improvement. The book includes 18 carefully reviewed chapters on recent developments in clinical trials and their statistical evaluation, with each chapter providing one or more examples involving typical data sets, enabling readers to apply the proposed procedures. The chapters employ a uniform style to enhance comparability between the approaches.

  11. Clinical Trials

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    Full Text Available ... Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, ... required to have an IRB. Office for Human Research Protections The U.S. Department of Health and Human ...

  12. Hydraulic engine valve actuation system including independent feedback control

    Science.gov (United States)

    Marriott, Craig D

    2013-06-04

    A hydraulic valve actuation assembly may include a housing, a piston, a supply control valve, a closing control valve, and an opening control valve. The housing may define a first fluid chamber, a second fluid chamber, and a third fluid chamber. The piston may be axially secured to an engine valve and located within the first, second and third fluid chambers. The supply control valve may control a hydraulic fluid supply to the piston. The closing control valve may be located between the supply control valve and the second fluid chamber and may control fluid flow from the second fluid chamber to the supply control valve. The opening control valve may be located between the supply control valve and the second fluid chamber and may control fluid flow from the supply control valve to the second fluid chamber.

  13. The PACT trial: PAtient Centered Telerehabilitation

    Directory of Open Access Journals (Sweden)

    Andreas Stefan Rothgangel

    2015-01-01

    Discussion: Several questions concerning the study design that emerged during the preparation of this trial will be discussed. This will include how these questions were addressed and arguments for the choices that were made.

  14. Patient representatives? views on patient information in clinical cancer trials

    OpenAIRE

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-01-01

    Background Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives? views and perceptions on the written trial information used in clinical cancer trials. Methods Written patient information leaflet...

  15. Clinical efficacy of including capecitabine in neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Qiuyun Li

    Full Text Available BACKGROUND: Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients. METHODS: The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1. RESULTS: Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87-1.40, p = 0.43, pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83-1.18, p = 0.90, overall response rate (ORR; RR = 1.00, 95% CI 0.94-1.07, p = 0.93, or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93-1.04, p = 0.49. CONCLUSIONS: Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.

  16. Pharmaceutical companies' policies on access to trial data, results, and methods: audit study.

    Science.gov (United States)

    Goldacre, Ben; Lane, Síle; Mahtani, Kamal R; Heneghan, Carl; Onakpoya, Igho; Bushfield, Ian; Smeeth, Liam

    2017-07-26

    Objectives  To identify the policies of major pharmaceutical companies on transparency of trials, to extract structured data detailing each companies' commitments, and to assess concordance with ethical and professional guidance. Design  Structured audit. Setting  Pharmaceutical companies, worldwide. Participants  42 pharmaceutical companies. Main outcome measures  Companies' commitments on sharing summary results, clinical study reports (CSRs), individual patient data (IPD), and trial registration, for prospective and retrospective trials. Results  Policies were highly variable. Of 23 companies eligible from the top 25 companies by revenue, 21 (91%) committed to register all trials and 22 (96%) committed to share summary results; however, policies commonly lacked timelines for disclosure, and trials on unlicensed medicines and off-label uses were only included in six (26%). 17 companies (74%) committed to share the summary results of past trials. The median start date for this commitment was 2005. 22 companies (96%) had a policy on sharing CSRs, mostly on request: two committed to share only synopses and only two policies included unlicensed treatments. 22 companies (96%) had a policy to share IPD; 14 included phase IV trials (one included trials on unlicensed medicines and off-label uses). Policies in the exploratory group of smaller companies made fewer transparency commitments. Two companies fell short of industry body commitments on registration, three on summary results. Examples of contradictory and ambiguous language were documented and summarised by theme. 23/42 companies (55%) responded to feedback; 7/1806 scored policy elements were revised in light of feedback from companies (0.4%). Several companies committed to changing policy; some made changes immediately. Conclusions  The commitments made by companies to transparency of trials were highly variable. Other than journal submission for all trials within 12 months, all elements of best practice

  17. Challenges and Recent Progress in the Development of a Closed-loop Artificial Pancreas.

    Science.gov (United States)

    Bequette, B Wayne

    2012-12-01

    Pursuit of a closed-loop artificial pancreas that automatically controls the blood glucose of individuals with type 1 diabetes has intensified during the past six years. Here we discuss the recent progress and challenges in the major steps towards a closed-loop system. Continuous insulin infusion pumps have been widely available for over two decades, but "smart pump" technology has made the devices easier to use and more powerful. Continuous glucose monitoring (CGM) technology has improved and the devices are more widely available. A number of approaches are currently under study for fully closed-loop systems; most manipulate only insulin, while others manipulate insulin and glucagon. Algorithms include on-off (for prevention of overnight hypoglycemia), proportional-integral-derivative (PID), model predictive control (MPC) and fuzzy logic based learning control. Meals cause a major "disturbance" to blood glucose, and we discuss techniques that our group has developed to predict when a meal is likely to be consumed and its effect. We further examine both physiology and device-related challenges, including insulin infusion set failure and sensor signal attenuation. Finally, we discuss the next steps required to make a closed-loop artificial pancreas a commercial reality.

  18. Maximising the value of combining qualitative research and randomised controlled trials in health research: the QUAlitative Research in Trials (QUART) study--a mixed methods study.

    Science.gov (United States)

    O'Cathain, Alicia; Thomas, Kate J; Drabble, Sarah J; Rudolph, Anne; Goode, Jackie; Hewison, Jenny

    2014-06-01

    Researchers sometimes undertake qualitative research with randomised controlled trials (RCTs) of health interventions. To systematically explore how qualitative research is being used with trials and identify ways of maximising its value to the trial aim of providing evidence of effectiveness of health interventions. A sequential mixed methods study with four components. (1) Database search of peer-reviewed journals between January 2008 and September 2010 for articles reporting the qualitative research undertaken with specific trials, (2) systematic search of database of registered trials to identify studies combining qualitative research and trials, (3) survey of 200 lead investigators of trials with no apparent qualitative research and (4) semistructured telephone interviews with 18 researchers purposively sampled from the first three methods. Qualitative research was undertaken with at least 12% of trials. A large number of articles reporting qualitative research undertaken with trials (n=296) were published between 2008 and 2010. A total of 28% (82/296) of articles reported qualitative research undertaken at the pre-trial stage and around one-quarter concerned drugs or devices. The articles focused on 22 aspects of the trial within five broad categories. Some focused on more than one aspect of the trial, totalling 356 examples. The qualitative research focused on the intervention being trialled (71%, 254/356), the design and conduct of the trial (15%, 54/356), the outcomes of the trial (1%, 5/356), the measures used in the trial (3%, 10/356), and the health condition in the trial (9%, 33/356). The potential value of the qualitative research to the trial endeavour included improving the external validity of trials and facilitating interpretation of trial findings. This value could be maximised by using qualitative research more at the pre-trial stage and reporting findings with explicit attention to the implications for the trial endeavour. During interviews

  19. The impact of Asian American value systems on palliative care: illustrative cases from the family-focused grief therapy trial.

    Science.gov (United States)

    Mondia, Stephen; Hichenberg, Shira; Kerr, Erica; Eisenberg, Megan; Kissane, David W

    2012-09-01

    Clinicians meet people from different ethnic backgrounds, yet need to respond in culturally sensitive ways. This article focuses on Asian American families. Within a randomized controlled trial of family therapy commenced during palliative care and continued into bereavement, 3 families of Asian American background were examined qualitatively from a cultural perspective by listening to recordings of 26 therapy sessions and reviewing detailed supervision notes compiled by each therapist. A synopsis of each family's therapy narrative is presented. Prominent themes include family closeness, respect for hierarchy within the family, gender-determined roles, intergenerational tensions, preoccupation with shame and limited emotional expressiveness. Family therapists working with culturally diverse families need to pay thoughtful attention to ethnic issues as they strive to support them during palliative care and bereavement.

  20. Long-term dietary intervention trials: critical issues and challenges

    Directory of Open Access Journals (Sweden)

    Crichton Georgina E

    2012-07-01

    Full Text Available Abstract Background There are many challenges involved in running randomised controlled dietary intervention trials that investigate health outcomes. The aim of this paper was to evaluate the recruitment process, retention of participants and challenges faced in our dairy intervention trial, and to provide strategies to combat the difficulties of running long-term dietary intervention trials. Methods A 12-month, randomised, two-way crossover study was conducted in overweight adults with habitually low dairy food consumption to assess the effects of a high dairy intake (4 servings of reduced-fat dairy per day compared with a low dairy intake (1 serving of reduced-fat dairy per day on measures of cardiometabolic and cognitive health. On completion of the high dairy intake phase, each participant was interviewed about their experience in the trial and responses were used to evaluate the key issues for study participants. Results Although the recruitment target was achieved, high rates of attrition (49.3% and difficulties maintaining participant compliance (reported by 37.8% of participants were major threats to the viability of the study. Factors that contributed to the high attrition included inability to comply with the dietary requirements of the study protocol (27.0%, health problems or medication changes (24.3% and time commitment (10.8%. Conclusion Attrition and adherence to study requirements present challenges to trials requiring longer-term dietary change. Including a run-in period to further assess the motivation, commitment and availability of participants, maintaining regular contact with participants during control phases, minimising time commitment, providing flexibility with dietary requirements, facilitating positive experiences, and stringent monitoring of diet are some key recommendations for future dietary intervention trials. Trial registration Australia and New Zealand Clinical Trials Registry (ACTRN 12608000538347

  1. Clinical Trials

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    Full Text Available ... Health Topics / About Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, ... tool for advancing medical knowledge and patient care. Clinical research is done only if doctors don't know ...

  2. Recruitment of subjects into clinical trials for Alzheimer disease.

    Science.gov (United States)

    Knebl, Janice A; Patki, Deepti

    2010-09-01

    Alzheimer disease is a devastating neurodegenerative disorder affecting millions of Americans. It reduces the ability of the individual to remain independent, places a burden on caregivers, and substantially increases healthcare costs. New treatments are being tested in numerous clinical trials with the goal of preventing or delaying the onset of Alzheimer disease, slowing or modifying the disease's course, or finding a cure for patients with the disease. Alzheimer disease research can successfully proceed only if individuals who have this illness are willing to participate in clinical trials. However, recruitment and retention of subjects in clinical trials for Alzheimer disease is a challenging task. Furthermore, because of reductions in decision-making capacities of individuals with Alzheimer disease, clinical trials also need to involve caregivers. The present article delineates unique hurdles encountered in the recruitment process for Alzheimer disease clinical trials. The article also identifies strategies for effective recruitment of subjects in Alzheimer disease clinical trials, including guidelines to help principal investigators and clinical research coordinators reach recruitment goals.

  3. Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis.

    Directory of Open Access Journals (Sweden)

    Joseph S Ross

    2009-09-01

    Full Text Available ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication.We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515, nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46% of trials were published, among which 96 (31% provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357 were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001, but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22. Among trials that reported an end date, 75 of 123 (61% completed prior to 2004, 50 of 96 (52% completed during 2004, and 62 of 149 (42% completed during 2005 were published (p = 0.006.Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data

  4. Big Data in Designing Clinical Trials: Opportunities and Challenges.

    Science.gov (United States)

    Mayo, Charles S; Matuszak, Martha M; Schipper, Matthew J; Jolly, Shruti; Hayman, James A; Ten Haken, Randall K

    2017-01-01

    Emergence of big data analytics resource systems (BDARSs) as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs) have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

  5. Big Data in Designing Clinical Trials: Opportunities and Challenges

    Directory of Open Access Journals (Sweden)

    Charles S. Mayo

    2017-08-01

    Full Text Available Emergence of big data analytics resource systems (BDARSs as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

  6. Real-Time Enrollment Dashboard For Multisite Clinical Trials.

    Science.gov (United States)

    Mattingly, William A; Kelley, Robert R; Wiemken, Timothy L; Chariker, Julia H; Peyrani, Paula; Guinn, Brian E; Binford, Laura E; Buckner, Kimberley; Ramirez, Julio

    2015-10-30

    Achieving patient recruitment goals are critical for the successful completion of a clinical trial. We designed and developed a web-based dashboard for assisting in the management of clinical trial screening and enrollment. We use the dashboard to assist in the management of two observational studies of community-acquired pneumonia. Clinical research associates and managers using the dashboard were surveyed to determine its effectiveness as compared with traditional direct communication. The dashboard has been in use since it was first introduced in May of 2014. Of the 23 staff responding to the survey, 77% felt that it was easier or much easier to use the dashboard for communication than to use direct communication. We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are a useful tool for clinical trial management. They can be used as a standalone trial information tool or included into a larger management system.

  7. Cross-system evaluation of clinical trial search engines.

    Science.gov (United States)

    Jiang, Silis Y; Weng, Chunhua

    2014-01-01

    Clinical trials are fundamental to the advancement of medicine but constantly face recruitment difficulties. Various clinical trial search engines have been designed to help health consumers identify trials for which they may be eligible. Unfortunately, knowledge of the usefulness and usability of their designs remains scarce. In this study, we used mixed methods, including time-motion analysis, think-aloud protocol, and survey, to evaluate five popular clinical trial search engines with 11 users. Differences in user preferences and time spent on each system were observed and correlated with user characteristics. In general, searching for applicable trials using these systems is a cognitively demanding task. Our results show that user perceptions of these systems are multifactorial. The survey indicated eTACTS being the generally preferred system, but this finding did not persist among all mixed methods. This study confirms the value of mixed-methods for a comprehensive system evaluation. Future system designers must be aware that different users groups expect different functionalities.

  8. A web-based clinical trial management system for a sham-controlled multicenter clinical trial in depression.

    Science.gov (United States)

    Durkalski, Valerie; Wenle Zhao; Dillon, Catherine; Kim, Jaemyung

    2010-04-01

    Clinical trial investigators and sponsors invest vast amounts of resources and energy into conducting trials and often face daily challenges with data management, project management, and data quality control. Rather than waiting months for study progress reports, investigators need the ability to use real-time data for the coordination and management of study activities across all study team members including site investigators, oversight committees, data and safety monitoring boards, and medical safety monitors. Web-based data management systems are beginning to meet this need but what distinguishes one system from the other are user needs/requirements and cost. To illustrate the development and implementation of a web-based data and project management system for a multicenter clinical trial designed to test the superiority of repeated transcranial magnetic stimulation versus sham for the treatment of patients with major depression. The authors discuss the reasons for not using a commercially available system for this study and describe the approach to developing their own web-based system for the OPT-TMS study. Timelines, effort, system architecture, and lessons learned are shared with the hope that this information will direct clinical trial researchers and software developers towards more efficient, user-friendly systems. The developers use a combination of generic and custom application code to allow for the flexibility to adapt the system to the needs of the study. Features of the system include: central participant registration and randomization; secure data entry at the site; participant progress/study calendar; safety data reporting; device accounting; monitor verification; and user-configurable generic reports and built-in customized reports. Hard coding was more time-efficient to address project-specific issues compared with the effort of creating a generic code application. As a consequence of this strategy, the required maintenance of the system is

  9. Gatekeepers for pragmatic clinical trials.

    Science.gov (United States)

    Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven

    2015-10-01

    To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding

  10. The Globalization of Pediatric Research: An Analysis of Clinical Trials Completed for Pediatric Exclusivity

    Science.gov (United States)

    Pasquali, Sara K.; Burstein, Danielle S.; Benjamin, Daniel K.; Smith, P. Brian; Li, Jennifer S.

    2010-01-01

    Background Recent studies have examined the globalization of clinical research. These studies focused on adult trials, and the globalization of pediatric research has not been examined to date. We evaluated the setting of published studies conducted under the US Pediatric Exclusivity Program, which provides economic incentives to pharmaceutical companies to conduct drug studies in children. Methods Published studies containing the main results of trials conducted from 1998–2007 under the Pediatric Exclusivity Provision were included. Data were extracted from each study and described, including the therapeutic area of drug studied, number of patients enrolled, number of sites, and location where the study was conducted, if reported. Results Overall, 174 trials were included (sample size 8–27,065 patients); 9% did not report any information regarding the location or number of sites where the study was conducted. Of those that did report this information, 65% were conducted in at least one country outside the US, and 11% did not have any sites in the US. Fifty-four different countries were represented and 38% of trials enrolled patients in at least one site located in a developing/transition country, including more than one third of infectious disease, cardiovascular, and allergy/immunology trials. Conclusions The majority of published pediatric trials conducted under the Pediatric Exclusivity Provision included sites outside of the US, and over a third of trials enrolled patients in developing/transition countries. While there are many potential benefits to the globalization of pediatric research, this trend also raises certain scientific and ethical concerns which require further evaluation. PMID:20732941

  11. On a wave-particle in closed and open isotropic universes

    International Nuclear Information System (INIS)

    Campos, L. M. B. C.

    2011-01-01

    The Klein-Gordon equation satisfied by the wave function in general relativity is solved for the metric of the closed and open universe corresponding to Einstein-De Sitter-Friedmann isotropic cosmological model. The angular dependences are specified by spherical harmonics for the longitude and latitude, and for the hyperlatitude by modified spherical harmonics having as variable circular functions for the closed universe and hyperbolic functions for the open universes. The time dependence of the probabilistic wave function is similar for the closed and open universes and is obtained in the following three cases: (I) constant Hubble parameter, (II) constant decceleration parameter, and (III) uniform matter and energy distribution, which corresponds to the Hubble parameter a linear function of time. Thus six solutions are obtained, namely, the three cases I-III each for closed and open isotropic universes. For each of these six solutions is considered: (i) the existence of singularities in space-time including asymptotic time in the future or past, (ii) the square integrability of the wave function over the full extent of the four-dimensional space-time, and (iii) the existence or otherwise of a positive probability density associated with the wave function.

  12. Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: protocol for a feasibility randomized pilot trial.

    Science.gov (United States)

    Johnstone, Jennie; Meade, Maureen; Marshall, John; Heyland, Daren K; Surette, Michael G; Bowdish, Dawn Me; Lauzier, Francois; Thebane, Lehana; Cook, Deborah J

    2015-01-01

    Probiotics are defined as live microorganisms that may confer health benefits when ingested. Meta-analysis of probiotic trials suggests a 25 % lower ventilator-associated pneumonia (VAP) and 18 % lower infection rates overall when administered to patients in the intensive care unit (ICU). However, prior trials are small, largely single center, and at high risk of bias. Before a large rigorous trial is launched, testing whether probiotics confer benefit, harm, or have no impact, a pilot trial is needed. The aim of the PROSPECT Pilot Trial is to determine the feasibility of performing a larger trial in mechanically ventilated critically ill patients investigating Lactobacillus rhamnosus GG. A priori, we determined that the feasibility of the larger trial would be based on timely recruitment, high protocol adherence, minimal contamination, and an acceptable VAP rate. Patients ≥18 years old in the ICU who are anticipated to receive mechanical ventilation for ≥72 hours will be included. Patients are excluded if they are at increased risk of probiotic-associated infection, have strict enteral medication contraindications, are pregnant, previously enrolled in a related trial, or are receiving palliative care. Following informed consent, patients are randomized in variable unspecified block sizes in a fixed 1:1 ratio, stratified by ICU, and medical, surgical, or trauma admitting diagnosis. Patients receive 1 × 10 10 colony forming units of L. rhamnosus GG (Culturelle, Locin Industries Ltd) or an identical placebo suspended in tap water administered twice daily via nasogastric tube in the ICU. Clinical and research staff, patients, and families are blinded. The primary outcomes for this pilot trial are the following: (1) recruitment success, (2) ≥90 % protocol adherence, (3) ≤5 % contamination, and (4) ~10 % VAP rate. Additional clinical outcomes are VAP, other infections, diarrhea (total, antibiotic associated, and Clostridium difficile), ICU and

  13. [Early clinical trials in paediatric oncology in Spain: a nationwide perspective].

    Science.gov (United States)

    Bautista, Francisco; Gallego, Soledad; Cañete, Adela; Mora, Jaume; Díaz de Heredia, Cristina; Cruz, Ofelia; Fernández, José María; Rives, Susana; Berlanga, Pablo; Hladun, Raquel; Juan Ribelles, Antonio; Madero, Luis; Ramírez, Manuel; Fernández Delgado, Rafael; Pérez-Martínez, Antonio; Mata, Cristina; Llort, Anna; Martín Broto, Javier; Cela, María Elena; Ramírez, Gema; Sábado, Constantino; Acha, Tomás; Astigarraga, Itziar; Sastre, Ana; Muñoz, Ascensión; Guibelalde, Mercedes; Moreno, Lucas

    2017-09-01

    Cancer is the leading cause of death between the first year of life and adolescence, and some types of diseases are still a major challenge in terms of cure. There is, therefore, a major need for new drugs. Recent findings in cancer biology open the door to the development of targeted therapies against individual molecular changes, as well as immunotherapy. Promising results in adult anti-cancer drug development have not yet been translated into paediatric clinical practice. A report is presented on the activity in early paediatric oncology trials (phase I-II) in Spain. All members of the Spanish Society of Paediatric Haematology Oncology (SEHOP) were contacted in order to identify early clinical trials in paediatric cancer opened between 2005 and 2015. A total of 30 trials had been opened in this period: 21 (70%) in solid tumours, and 9 (30%) in malignant haemopathies. A total of 212 patients have been enrolled. The majority was industry sponsored (53%). Since 2010, four centres have joined the international consortium of Innovative Therapies for Children with Cancer (ITCC), which has as its aim to develop novel therapies for paediatric tumours. A significant number of new studies have opened since 2010, improving the treatment opportunities for our children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents, and their benefits. The activity in clinical trials has increased in the years analysed. The SEHOP is committed to develop and participate in collaborative academic trials, in order to help in the advancement and optimisation of existing therapies in paediatric cancer. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Forty-five years of schizophrenia trials in Italy: a survey

    Directory of Open Access Journals (Sweden)

    Purgato Marianna

    2012-04-01

    Full Text Available Abstract Background Well-designed and properly executed randomized controlled trials (RCTs provide the best evidence on the efficacy of healthcare interventions. Mental health has a strong tradition of using trial to evaluate treatments, but the translation of research to clinical practice is not always easy. Even well-conducted trials do not necessarily address the needs of every day care and trials can reflect local needs and the specific culture in which they are undertaken. Generalizing results to other contexts can become problematic but these trials may, nevertheless, be very helpful within their own context. Moreover, pathways for drug approval can be different depending on local regulatory agencies. Local trials are helpful for decision-making in the region from which they come, but should not be viewed in isolation. National quantity and quality of trials may vary across nations. The aim of this study is to quantify trialing activity in Italy from 1948 until 2009 and to describe characteristics of these trials. In addition, we evaluated change over time in three keys aspects: sample size, follow-up duration, and number of outcomes. Methods We used the Cochrane Schizophrenia Group's register that contains 16,000 citations to 13,000 studies relating only to people with schizophrenia or schizophrenia-like illness. Randomized controlled trials and controlled clinical trials undertaken in Italy and involving pharmacological interventions were included. Results The original search identified 155 records of potentially eligible studies, 74 of which were excluded because do not meet inclusion criteria. A total of 81 studies were included in the analysis. The majority of trials were conducted in north Italy, and published in international journals between 1981 and 1995. The majority of studies (52 out of 81 used standardized diagnostic criteria for schizophrenia disorder. They were defined as randomized and used blind methods to administer

  15. Randomised controlled trials and changing public health practice

    Directory of Open Access Journals (Sweden)

    Anne Cockcroft

    2017-05-01

    Full Text Available Abstract One reason for doing randomised controlled trials (RCTs is that experiments can be convincing. Early epidemiological experimenters, such as Jenner and the smallpox vaccine and Snow and his famous Broad Street pump handle, already knew the answer they were demonstrating; they used the experiments as knowledge translation devices to convince others. More sophisticated modern experiments include cluster randomised controlled trials (CRCTs for experiments in the public health setting. The knowledge translation value remains: RCTs and CRCTs can potentially stimulate changes of practice among stakeholders. Capitalising on the knowledge translation value of RCTs requires more than the standard reporting of trials. Those who are convinced by a trial and want to act, need to know how the trial relates to their own context, what contributed to success, and what might make it even more effective. Implementation research unpacks the back-story, examining how and why an intervention worked. The Camino Verde trial of community mobilisation for control of dengue reported a significant impact on entomological indices of the Aedes aegypti vector, and on serological dengue virus infection and self-reported dengue cases. This important study should lead to studies of similar interventions in other contexts, and ultimately to changes in dengue control practices. This supplement is the back-story of the trial, providing information to help researchers and planners to make use of the trial findings. Background articles include the full protocol, a systematic review of CRCTs of approaches for Aedes aegypti control, epidemiological and entomological findings from the baseline survey, and how baseline findings were used to set up the intervention. Secondary analyses of the entomological findings examine associations with the use of the larvicide temephos, and the impact of the intervention in different conditions of water supply and seasons. Other articles

  16. Oriented open-closed string theory revisited

    International Nuclear Information System (INIS)

    Zwiebach, B.

    1998-01-01

    String theory on D-brane backgrounds is open-closed string theory. Given the relevance of this fact, we give details and elaborate upon our earlier construction of oriented open-closed string field theory. In order to incorporate explicitly closed strings, the classical sector of this theory is open strings with a homotopy associative A ∞ algebraic structure. We build a suitable Batalin-Vilkovisky algebra on moduli spaces of bordered Ricmann surfaces, the construction of which involves a few subtleties arising from the open string punctures and cyclicity conditions. All vertices coupling open and closed strings through disks are described explicitly. Subalgebras of the algebra of surfaces with boundaries are used to discuss symmetries of classical open string theory induced by the closed string sector, and to write classical open string field theory on general closed string backgrounds. We give a preliminary analysis of the ghost-dilaton theorem. copyright 1998 Academic Press, Inc

  17. Co-enrolment of Participants into Multiple Cancer Trials: Benefits and Challenges.

    Science.gov (United States)

    Cafferty, F H; Coyle, C; Rowley, S; Berkman, L; MacKensie, M; Langley, R E

    2017-07-01

    Opportunities to enter patients into more than one clinical trial are not routinely considered in cancer research and experiences with co-enrolment are rarely reported. Potential benefits of allowing appropriate co-enrolment have been identified in other settings but there is a lack of evidence base or guidance to inform these decisions in oncology. Here, we discuss the benefits and challenges associated with co-enrolment based on experiences in the Add-Aspirin trial - a large, multicentre trial recruiting across a number of tumour types, where opportunities to co-enrol patients have been proactively explored and managed. The potential benefits of co-enrolment include: improving recruitment feasibility; increased opportunities for patients to participate in trials; and collection of robust data on combinations of interventions, which will ensure the ongoing relevance of individual trials and provide more cohesive evidence to guide the management of future patients. There are a number of perceived barriers to co-enrolment in terms of scientific, safety and ethical issues, which warrant consideration on a trial-by-trial basis. In many cases, any potential effect on the results of the trials will be negligible - limited by a number of factors, including the overlap in trial cohorts. Participant representatives stress the importance of autonomy to decide about trial enrolment, providing a compelling argument for offering co-enrolment where there are multiple trials that are relevant to a patient and no concerns regarding safety or the integrity of the trials. A number of measures are proposed for managing and monitoring co-enrolment. Ensuring acceptability to (potential) participants is paramount. Opportunities to enter patients into more than one cancer trial should be considered more routinely. Where planned and managed appropriately, co-enrolment can offer a number of benefits in terms of both scientific value and efficiency of study conduct, and will increase the

  18. Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Christensen, Anton Wulf; Tarp, Simon; Furst, Daniel E

    2015-01-01

    OBJECTIVE: To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs....... Odds ratios (ORs) were calculated from the response rates and compared among the trial eligibility criteria/patient baseline characteristics of interest. Comparisons are presented as the Ratio of Odds Ratios (ROR). RESULTS: Sixty-two trials (19,923 RA patients) were included in the primary analyses...... using ACR20 response. Overall, targeted therapies constituted an effective treatment (OR 3.96 95% confidence interval (CI) 3.41 to 4.60). The majority of the trial eligibility criteria and patient baseline characteristics did not modify treatment effect. The added benefit of targeted therapies was lower...

  19. Clinical Trials

    Medline Plus

    Full Text Available ... child to enroll. Also, children aged 7 and older often must agree (assent) to take part in clinical trials. Clinical trials for children have the same scientific safeguards as clinical trials for adults. For more information, go to "How Do Clinical ...

  20. Clinical Trials

    Medline Plus

    Full Text Available ... give permission for their child to enroll. Also, children aged 7 and older often must agree (assent) to take part in clinical trials. Find a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...

  1. Are You "Tilting at Windmills" or Undertaking a Valid Clinical Trial?

    Science.gov (United States)

    Zariffa, Jose; Kramer, John L.K.

    2011-01-01

    In this review, several aspects surrounding the choice of a therapeutic intervention and the conduct of clinical trials are discussed. Some of the background for why human studies have evolved to their current state is also included. Specifically, the following questions have been addressed: 1) What criteria should be used to determine whether a scientific discovery or invention is worthy of translation to human application? 2) What recent scientific advance warrants a deeper understanding of clinical trials by everyone? 3) What are the different types and phases of a clinical trial? 4) What characteristics of a human disorder should be noted, tracked, or stratified for a clinical trial and what inclusion /exclusion criteria are important to enrolling appropriate trial subjects? 5) What are the different study designs that can be used in a clinical trial program? 6) What confounding factors can alter the accurate interpretation of clinical trial outcomes? 7) What are the success rates of clinical trials and what can we learn from previous clinical trials? 8) What are the essential principles for the conduct of valid clinical trials? PMID:21786433

  2. Improving ethical and participatory practice for marginalized populations in biomedical HIV prevention trials: lessons from Thailand.

    Directory of Open Access Journals (Sweden)

    Dan Allman

    Full Text Available BACKGROUND: This paper presents findings from a qualitative investigation of ethical and participatory issues related to the conduct of biomedical HIV prevention trials among marginalized populations in Thailand. This research was deemed important to conduct, as several large-scale biomedical HIV prevention trials among marginalized populations had closed prematurely in other countries, and a better understanding of how to prevent similar trial closures from occurring in the future was desired. METHODS: In-depth key informant interviews were held in Bangkok and Chiang Mai, Thailand. Interviews were audio recorded, transcribed, translated and thematically analyzed. The Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials (GPP guided this work. RESULTS: Fourteen interviews were conducted: 10 with policymakers, academic and community-based researchers and trial staff and four with representatives of non-governmental organizations (NGOs. Suggested ways to improve ethical and participatory practice centered on standards of HIV prevention, informed consent, communication and human rights. In particular, the need to overcome language and literacy differences was identified. Key informants felt communication was the basis of ethical understanding and trust within biomedical HIV prevention trial contexts, and thus fundamental to trial participants' ability to exercise free will. DISCUSSION: Biomedical HIV prevention trials present opportunities for inclusive and productive ethical and participatory practice. Key informants suggested that efforts to improve practice could result in better relationships between research stakeholders and research investigative teams and by extension, better, more ethical participatory trials. This research took place in Thailand and its findings apply primarily to Thailand. However, given the universality of many ethical considerations, the results of this study can inform the improvement of ethical

  3. Improving ethical and participatory practice for marginalized populations in biomedical HIV prevention trials: lessons from Thailand.

    Science.gov (United States)

    Allman, Dan; Ditmore, Melissa Hope; Kaplan, Karyn

    2014-01-01

    This paper presents findings from a qualitative investigation of ethical and participatory issues related to the conduct of biomedical HIV prevention trials among marginalized populations in Thailand. This research was deemed important to conduct, as several large-scale biomedical HIV prevention trials among marginalized populations had closed prematurely in other countries, and a better understanding of how to prevent similar trial closures from occurring in the future was desired. In-depth key informant interviews were held in Bangkok and Chiang Mai, Thailand. Interviews were audio recorded, transcribed, translated and thematically analyzed. The Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials (GPP) guided this work. Fourteen interviews were conducted: 10 with policymakers, academic and community-based researchers and trial staff and four with representatives of non-governmental organizations (NGOs). Suggested ways to improve ethical and participatory practice centered on standards of HIV prevention, informed consent, communication and human rights. In particular, the need to overcome language and literacy differences was identified. Key informants felt communication was the basis of ethical understanding and trust within biomedical HIV prevention trial contexts, and thus fundamental to trial participants' ability to exercise free will. Biomedical HIV prevention trials present opportunities for inclusive and productive ethical and participatory practice. Key informants suggested that efforts to improve practice could result in better relationships between research stakeholders and research investigative teams and by extension, better, more ethical participatory trials. This research took place in Thailand and its findings apply primarily to Thailand. However, given the universality of many ethical considerations, the results of this study can inform the improvement of ethical and participatory practice in other parts of the world where

  4. How completely are physiotherapy interventions described in reports of randomised trials?

    Science.gov (United States)

    Yamato, Tiê P; Maher, Chris G; Saragiotto, Bruno T; Hoffmann, Tammy C; Moseley, Anne M

    2016-06-01

    Incomplete descriptions of interventions are a common problem in reports of randomised controlled trials. To date no study has evaluated the completeness of the descriptions of physiotherapy interventions. To evaluate the completeness of the descriptions of physiotherapy interventions in a random sample of reports of randomised controlled trials (RCTs). A random sample of 200 reports of RCTs from the PEDro database. We included full text papers, written in English, and reporting trials with two arms. We included trials evaluating any type of physiotherapy interventions and subdisciplines. The methodological quality was evaluated using the PEDro scale and completeness of intervention description using the Template for Intervention Description and Replication (TIDieR) checklist. The proportion and 95% confidence interval were calculated for intervention and control groups, and used to present the relationship between completeness and methodological quality, and subdisciplines. Completeness of intervention reporting in physiotherapy RCTs was poor. For intervention groups, 46 (23%) trials did not describe at least half of the items. Reporting was worse for control groups, 149 (75%) trials described less than half of the items. There was no clear difference in the completeness across subdisciplines or methodological quality. Our sample were restricted to trials published in English in 2013. Descriptions of interventions in physiotherapy RCTs are typically incomplete. Authors and journals should aim for more complete descriptions of interventions in physiotherapy trials. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  5. Gender differences in clinical registration trials: is there a real problem?

    Science.gov (United States)

    Labots, Geert; Jones, Aubrey; de Visser, Saco J.; Burggraaf, Jacobus

    2018-01-01

    Aims Several studies have reported the under‐representation of women in clinical trials, thereby challenging the external validity of the benefit/risk assessments of launched drugs. Our aim was to determine the extent to which women have been included in clinical trials used for drug registration and to analyse the fraction of women participating in phases I, II and III. Methods We conducted cross‐sectional, structured research into publicly available registration dossiers of Food and Drug Administration (FDA)‐approved drugs that are prescribed frequently. Furthermore, we analysed compounds with high hepatic clearance and a known gender‐related difference in drug response. In a sensitivity analysis, we compared figures with US disease prevalence data. Results For 38 of the initial 137 drugs (28%), sufficient data were reported and publicly available. For these drugs, 185 479 trial participants were included, of whom 47% were female and 44% were male; gender was not reported for 9% of participants. However, the number of female participants varied with the phase of the trial, with 22% females in phase I trials vs. 48% and 49%, respectively, in phase II and III trials. When compared with US disease prevalence data, 10 drugs (26%) had a greater than 20% difference between the proportion of females affected with the disease compared with representation in clinical trials. Conclusions From these publicly available data, there was no evidence of any systematic under‐representation of women in clinical trials. PMID:29293280

  6. Adaptive trials for tuberculosis: early reflections on theory and practice.

    Science.gov (United States)

    Montgomery, C M

    2016-08-01

    Adaptive designs (ADs) have been proposed for anti-tuberculosis treatment trials. This call for innovation occurs against the backdrop of fundamental changes in the acceptable evidence base in anti-tuberculosis treatment. To contextualise ADs for tuberculosis (TB) and explore early responses from those working in the field. In this qualitative study investigating processes of theoretical and practical change in randomised controlled trials, 24 interviews were conducted with professionals involved in AD trials, half of whom worked in the TB field. Clinical trialists working on AD trials in TB are positive about the efficiency these designs offer, but remain cautious about their suitability. In addition to technical concerns, informants discussed the challenges of implementing AD in developing countries, including limited regulatory capacity to evaluate proposals, investments needed in infrastructure and site capacity, and challenges regarding informed consent. Respondents identified funding, interdisciplinary communication and regulatory and policy responses as additional concerns potentially affecting the success of AD for TB. Empirical research is needed into patient experiences of AD, including informed consent. Further consideration of the contexts of innovation in trial design is needed. These are fundamental to the successful translation of theory into practice.

  7. Assessing Clinical Trial-Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool.

    Science.gov (United States)

    Good, Marjorie J; Hurley, Patricia; Woo, Kaitlin M; Szczepanek, Connie; Stewart, Teresa; Robert, Nicholas; Lyss, Alan; Gönen, Mithat; Lilenbaum, Rogerio

    2016-05-01

    Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings. Community-based research programs were recruited to collect and enter clinical trial-associated monthly workload data into a web-based tool for 6 consecutive months. Descriptive statistics were computed for self-reported program characteristics and workload data, including staff acuity scores and number of patient encounters. Fifty-one research programs that represented 30 states participated. Median staff acuity scores were highest for staff with patients enrolled in studies and receiving treatment, relative to staff with patients in follow-up status. Treatment trials typically resulted in higher median staff acuity, relative to cancer control, observational/registry, and prevention trials. Industry trials exhibited higher median staff acuity scores than trials sponsored by the National Institutes of Health/National Cancer Institute, academic institutions, or others. The results from this project demonstrate that trial-specific acuity measurement is a better measure of workload than simply counting the number of patients. The tool was shown to be feasible and useable in diverse community-based research settings. Copyright © 2016 by American Society of Clinical Oncology.

  8. Managing clinical trials

    Directory of Open Access Journals (Sweden)

    Kenyon Sara

    2010-07-01

    Full Text Available Abstract Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation.

  9. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Scherer, Roberta W; Drye, Lea; Mintzer, Jacobo; Lanctôt, Krista; Rosenberg, Paul; Herrmann, Nathan; Padala, Prasad; Brawman-Mintzer, Olga; Burke, William; Craft, Suzanne; Lerner, Alan J; Levey, Allan; Porsteinsson, Anton; van Dyck, Christopher H

    2018-01-18

    Alzheimer's disease (AD) is characterized not only by cognitive and functional decline, but also often by the presence of neuropsychiatric symptoms. Apathy, which can be defined as a lack of motivation, is one of the most prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality of life and greater burden for caregivers. Treatment options for apathy in AD are limited, but studies have examined the use of the amphetamine, methylphenidate. The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of apathy in AD with methylphenidate was associated with significant improvement in apathy in two of three outcome measures, some evidence of improvement in global cognition, and minimal adverse events. However, the trial only enrolled 60 participants who were followed for only 6 weeks. A larger, longer-lasting trial is required to confirm these promising findings. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is a phase III, placebo-controlled, masked, 6-month, multi-center, randomized clinical trial targeted to enroll 200 participants with AD and apathy. Participants are randomly assigned 1:1 to 20 mg methylphenidate per day prepared as four over-encapsulated tablets or to matching placebo. The primary outcomes include (1) the mean difference in the Neuropsychiatric Inventory Apathy subscale scores measured as change from baseline to 6 months, and (2) the odds of having a given rating or better on the modified AD Cooperative Study Clinical Global Impression of Change ratings at month 6 compared with the baseline rating. Other outcomes include change in cognition, safety, and cost-effectiveness measured at monthly follow-up visits up to 6 months. Given the prevalence of apathy in AD and its impact on both patients and caregivers, an intervention to alleviate apathy would be of great benefit to society. ADMET 2 follows on the promising results from the original ADMET to evaluate the efficacy of methylphenidate as a

  10. Clinical Trials

    Medline Plus

    Full Text Available ... more screening tests to see which test produces the best results. Some companies and groups sponsor clinical trials that test the ... and Drug Administration (FDA) oversees these clinical trials. The NIH may partner with these companies or groups to help sponsor some trials. All ...

  11. The Steroids for Corneal Ulcers Trial

    Science.gov (United States)

    Srinivasan, Muthiah; Mascarenhas, Jeena; Rajaraman, Revathi; Ravindran, Meenakshi; Lalitha, Prajna; Glidden, David V.; Ray, Kathryn J.; Hong, Kevin C.; Oldenburg, Catherine E.; Lee, Salena M.; Zegans, Michael E.; McLeod, Stephen D.; Lietman, Thomas M.; Acharya, Nisha R.

    2013-01-01

    Objectives To provide comprehensive trial methods and baseline data for the Steroids for Corneal Ulcers Trial and to present epidemiological characteristics such as risk factors, causative organisms, and ulcer severity. Methods Baseline data from a 1:1 randomized, placebo-controlled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle-corrected visual acuity, infiltrate size, microbio-logical results, and patient demographics, for patients enrolled in the trial. Results Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 logMAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P=.04) and deeper infiltrates (P=.04) and were more likely to be localized centrally (P=.002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n=366, 72%). Conclusions The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation. PMID:21987581

  12. Closing the Knowledge Gap in Foreign Markets

    DEFF Research Database (Denmark)

    Lyles, Marjorie A.; Pedersen, Torben; Petersen, Bent

    The study explores how firms close their knowledge gaps in relation to business environments of foreign markets. Potential determinants are derived from traditional internationalization process theory as well as more recent literature on organizational learning processes, including the concept...... of absorptive capacity. Building on these two literature streams a conceptual model is developed and tested on a set of primary data of Danish firms and their foreign market operations. The empirical study suggests that factors considered essential in traditional internationalization process theory...

  13. Clinical trial allocation in multinational pharmaceutical companies – a qualitative study on influential factors

    DEFF Research Database (Denmark)

    Dombernowsky, Tilde; Haedersdal, Merete; Lassen, Ulrik

    2017-01-01

    (1) to identify key decision makers during country and site selection, respectively, (2) to evaluate by which parameters subsidiaries are primarily assessed by headquarters with regard to conducting clinical trials, and (3) to evaluate which site-related qualities companies value most when selecting......Clinical trial allocation in multinational pharmaceutical companies includes country selection and site selection. With emphasis on site selection, the overall aim of this study was to examine which factors pharmaceutical companies value most when allocating clinical trials. The specific aims were...... trial sites. Eleven semistructured interviews were conducted among employees engaged in trial allocation at 11 pharmaceutical companies. The interviews were analyzed by deductive content analysis, which included coding of data to a categorization matrix containing categories of site-related qualities...

  14. Smart Technology in Lung Disease Clinical Trials.

    Science.gov (United States)

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. Published by Elsevier Inc.

  15. Oxygen Consumption of Tilapia and Preliminary Mass Flows through a Prototype Closed Aquaculture System

    Science.gov (United States)

    Muller, Matthew S.; Bauer, Clarence F.

    1994-01-01

    Performance of NASA's prototype CELSS Breadboard Project Closed Aquaculture System was evaluated by estimating gas exchange quantification and preliminary carbon and nitrogen balances. The total system oxygen consumption rate was 535 mg/hr kg/fish (cv = 30%) when stocked with Tilapia aurea populations (fresh weights of 97 +/- 19 to 147 +/- 36 g/fish for various trials). Oxygen consumption by T. aurea (260 mg/hr kg/fish) contributed to approximately one-half of total system demand. Continuous carbon dioxide quantification methods were analyzed using the,relation of carbon dioxide to oxygen consumption. Overall food conversion rates averaged 18.2 +/- 3.2%. Major pathways for nitrogen and carbon in the system were described with preliminary mass closure of 60-80% and 60% for nitrogen and carbon.

  16. High current vacuum closing switch

    International Nuclear Information System (INIS)

    Dolgachev, G.I.; Maslennikov, D.D.; Romanov, A.S.; Ushakov, A.G.

    2005-01-01

    The paper proposes a powerful pulsed closing vacuum switch for high current commutation consisting of series of the vacuum diodes with near 1 mm gaps having closing time determined by the gaps shortening with the near-electrode plasmas [ru

  17. Magnitude of effects in clinical trials published in high-impact general medical journals.

    Science.gov (United States)

    Siontis, Konstantinos C M; Evangelou, Evangelos; Ioannidis, John P A

    2011-10-01

    Prestigious journals select for publication studies that are considered most important and informative. We aimed to examine whether high-impact general (HIG) medical journals systematically demonstrate more favourable results for experimental interventions compared with the rest of the literature. We scrutinized systematic reviews of the Cochrane Database (Issue 4, 2009) and meta-analyses published in four general journals (2008-09). Eligible articles included ≥1 binary outcome meta-analysis(es) pertaining to effectiveness with ≥1 clinical trial(s) published in NEJM, JAMA or Lancet. Effect sizes in trials from NEJM, JAMA or Lancet were compared with those from other trials in the same meta-analyses by deriving summary relative odds ratios (sRORs). Additional analyses examined separately early- and late-published trials in HIG journals and journal-specific effects. A total of 79 meta-analyses including 1043 clinical trials were analysed. Trials in HIG journals had similar effects to trials in other journals, when there was large-scale evidence, but showed more favourable results for experimental interventions when they were small. When HIG trials had less than 40 events, the sROR was 1.64 [95% confidence interval (95% CI): 1.23-2.18). The difference was most prominent when small early trials published in HIG journals were compared with subsequent trials [sROR 2.68 (95% CI: 1.33-5.38)]. Late-published HIG trials showed no consistent inflation of effects. The patterns did not differ beyond chance between NEJM, JAMA or Lancet. Small trials published in the most prestigious journals show more favourable effects for experimental interventions, and this is most prominent for early-published trials in such journals. No effect inflation is seen for large trials.

  18. Clinical Trials

    Medline Plus

    Full Text Available ... resources to the strategies and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, you may get tests or treatments in a hospital, clinic, or doctor's office. In some ways, taking part in a clinical trial is different ...

  19. Three dimensional model for particle saltation close to stream beds, including a detailed description of the particle interaction with turbulence and inter-particle collisions

    KAUST Repository

    Moreno, Pablo M.

    2011-05-19

    We present in this paper a new three-dimensional (3-D) model for bed-load sediment transport, based on a Lagrangian description. We analyze generalized sub-models for the velocities after collision and the representation of the bed-roughness. The free-flight sub-model includes the effect of several forces, such as buoyancy, drag, virtual mass, lift, Basset and Magnus, and also addresses the particle rotation. A recent methodology for saving computational time in the Basset force is also employed. The sub-models for the post-collision velocity and rotation are based on the conservation of linear and angular momentum during the collision with the bed. We develop a new 3-D representation for the bed roughness by using geometric considerations. In order to address the interaction of particles with the turbulent flow, we tracked the particles through a computed turbulent velocity field for a smooth flat plate. This velocity field was used as a surrogate of the 3-D turbulent conditions close to the bed in streams. We first checked that the basic turbulence statistics for this velocity field could be used to approximate those in an open-channel flow. We then analyzed the interaction of the sediment and the turbulence for a single and multiple particles. We compared numerical results with experimental data obtained by Niño and García (1998b). We show that model predictions are in good agreement with existing data, in the sand size range. © 2011 ASCE.

  20. Three dimensional model for particle saltation close to stream beds, including a detailed description of the particle interaction with turbulence and inter-particle collisions

    KAUST Repository

    Moreno, Pablo M.; Bombardelli, Fabiá n A.; Gonzá lez, Andrea E.; Calo, Victor M.

    2011-01-01

    We present in this paper a new three-dimensional (3-D) model for bed-load sediment transport, based on a Lagrangian description. We analyze generalized sub-models for the velocities after collision and the representation of the bed-roughness. The free-flight sub-model includes the effect of several forces, such as buoyancy, drag, virtual mass, lift, Basset and Magnus, and also addresses the particle rotation. A recent methodology for saving computational time in the Basset force is also employed. The sub-models for the post-collision velocity and rotation are based on the conservation of linear and angular momentum during the collision with the bed. We develop a new 3-D representation for the bed roughness by using geometric considerations. In order to address the interaction of particles with the turbulent flow, we tracked the particles through a computed turbulent velocity field for a smooth flat plate. This velocity field was used as a surrogate of the 3-D turbulent conditions close to the bed in streams. We first checked that the basic turbulence statistics for this velocity field could be used to approximate those in an open-channel flow. We then analyzed the interaction of the sediment and the turbulence for a single and multiple particles. We compared numerical results with experimental data obtained by Niño and García (1998b). We show that model predictions are in good agreement with existing data, in the sand size range. © 2011 ASCE.

  1. Multimodal interventions including nutrition in the prevention and management of disease-related malnutrition in adults: a systematic review of randomised control trials.

    Science.gov (United States)

    Thorne, Frances; Baldwin, Christine

    2014-06-01

    There has been a move to improve nutritional status in malnourished patients through the use of multimodal interventions (MI). There are currently no systematic reviews that have examined their effectiveness. This analysis aimed to examine the effects on nutritional, clinical, functional and patient-centred outcomes. A systematic review and meta-analysis using Cochrane methodology. 15 studies were included in the analysis, 13 comparing MI with usual care and 2 comparing MI with a nutrition intervention alone. Quality of studies varied and studies reported few relevant outcomes. Only 3 outcomes were compatible with meta-analysis; weight, mortality and length of stay (LOS). No statistically significant differences between groups were found. Narrative review was inconclusive. There was no evidence of benefit in the intervention groups in relation to body composition, functional status or quality of life (QoL). Intervention groups appeared to show a trend towards increased energy and protein intake however data was provided by only 2 studies (301 participants). No conclusive evidence of benefit for MI on any of the reviewed outcomes was found. Well designed, high quality trials addressing the impact of MI on relevant nutritional, functional and clinical outcomes are required. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. Clinical